NO/cGMP信号通路在新生和未成熟雌性大鼠卵泡形成和发育中的生物学作用及其调控机制研究
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摘要
雌性大鼠原始卵泡的形成发生在出生后,从刚出生时卵巢中卵母细胞巢开始发育,相当一部分卵泡在不同发育阶段相继退化闭锁,而另一部分到初情期前形成部分有腔卵泡。其中有两个方面的重要现象目前引发了人们极大地研究兴趣：1.卵母细胞巢如何裂解形成原始卵泡,并且在初情期前形成有腔卵泡。2.初情期前卵泡退化闭锁的影响因子是什么、其调控机制又是怎样?
NO/cGMP信号通路在雌性动物生殖生理过程中起着非常广泛的调节作用,诸如介导卵泡闭锁,类固醇,前列腺素的合成,排卵,卵母细胞的生长和成熟卵巢功能等。目前,还没有研究报道NO/cGMP信号通路在新生雌性大鼠卵泡发育过程中的生物学作用及其可能的调控机制。本研究采用组织形态学(HE)、免疫组织化学(IHC)、RT-PCR、免疫印迹(Western blot)等生物化学分子生物学研究技术,全面研究NO/cGMP信号通路在新生雌性大鼠从出生到初情期前卵泡发育过程中的生物学作用和调控机制。其主要发现和结论如下：
1.探讨三种不同的一氧化氮合酶(NOS)亚型在细胞内的表达以及相关的一氧化氮(NO)/环磷酸鸟苷(cGMP)的信号通路在新生和初情期前的雌性大鼠卵巢中的变化。发现,在出生后1天,5,7,10和19天,所有三个亚型的NOS,主要定位于各阶段卵泡的卵母细胞中,并在颗粒细胞和卵泡膜细胞内的增长逐步增加。卵巢总NOS活性和NO水平与其他在产后7日和10日相比,呈显著性增加。与内皮型NOS(eNOS)的,诱导型NOS (iNOS)相比,神经型NOS(nNOS)的活性则保持较低水平。我们的研究结果表明,内源性NOS/cGMP信号系统参与新生雌性大鼠卵泡发育。
2.采用RT-PCR法检测和半定量分析11种cGMP相关磷酸二酯酶在新生雌性大鼠卵巢发育过程中(出生后1,5,7,10,19天)的表达变化。结果发现：只有PDE1A, PDE3A, PDE3B, PDE5A, PDE9A有表达,其它酶类均无表达。进一步的半定量分析,PDE5A, PDE3A是主要表达的酶类。两者在出生后第一天表达较低(p<0.05),但是其余时间点表达稳定,cGMP相关磷酸二酯酶的表达在5天后趋于稳定。这就说明PDE5A, PDE3A参与了新生雌性大鼠卵巢发育并对cGMP起着主要的调控作用。
3.建立体内的一氧化氮合成酶抑制模型,然后组织学观察统计分析不同处理组卵泡发育的动力学变化。我们发现,处理5,10,19天后,L-NAME+SMT处理组,其卵巢中卵泡发育缓慢,在19天时,有腔卵泡数目显著减少(p<0.05),而L-Arg组则呈现提早发育,其有腔卵泡数目显著增加(p<0.01)。进一步检测各处理组总NOS、三种NOS亚型的活性和NO含量,发现,L-NAME+SMT处理组上述指标显著下降(p<0.05),而L-Arg组则显著上升(p<0.01)。但是NOS抑制剂单处理组则与对照差异不显著。研究结果表明NOS参与了新生雌性大鼠的卵巢卵泡发育,并且促进卵泡的提早发育。
4.采用免疫组化、免疫印迹(Western blot)探讨NOS促进卵泡的提早发育的可能机制。免疫组化显示,PI3K/AKT/FoxO3a信号通路主要蛋白PTEN、AKT和FoxO3a在新生雌性大鼠卵泡发育过程中,主要定位于卵母细胞,在出生后19天时,在颗粒细胞也有部分表达,而且其免疫染色增强。进一步的免疫印迹分析,发现：NOS抑制剂L-NAME+SMT处理5,10,19天组,与对照相比,P13K/AKT/FoxO3a信号通路,PTEN表达上升,p-AKT、p-Fox03a表达显著下降。而NOS的底物(L-Arg)处理5,10,19天组,其PI3K/AKT/FoxO3a信号通路激活,即：PTEN表达显著下降,p-AKT、p-FoxO3a表达显著上升。此外,同一处理时间,单注射NOS抑制剂L-NAME或sMT处理组与对照相比则没有显著变化。上述发现说明NOS参与了新生雌性大鼠的卵巢卵泡发育,并且可以通过P13K/AKT/Foxo3a信号通路促进卵泡的提早发育。
5.采用免疫组化、免疫印迹(Western blot)探讨NOS是否通过细胞自噬和凋亡参与新生雌性大鼠卵巢发育。结果发现,凋亡标记蛋白(Caspase-3)和自噬标记蛋白(LC3)在新生大鼠卵巢普遍分布,从出生5天后,主要分布在颗粒细胞,卵母细胞,膜细胞等,进一步的WB检测,NOs抑制剂L-NAME+SMT处理5,10,19天组,与对照相比,LC3-Ⅱ表达下降,Cleaved-caspase-3表达显著上升。而NOS的底物(L-Arg)处理5,10,19天组,其LC3-Ⅱ表达上升,Cleaved-caspase-3表达显著下降。此外,同一处理时间,单注射NOS抑制剂L-NAME或SMT处理组与对照相比则没有显著变化。上述结果证实NOS通过细胞自噬和凋亡参与新生雌性大鼠卵巢发育。
The primordial follicle formation and development in the rat ovary initiates after birth. Originally from egg nests, most follicles go atresia during postnatal days at different developmental stages, the other follicles grow into antral follicles. There are two important phenomenons attract attentions of scientists:1. How the primordial follicle formation from egg nests and grows as antral follicle?2. What impact factors and regulation mechanisms of follicular atresia are contained in the ovary before puberty? The NO/cGMP pathway regulates significantly the biologic and physiologic processes of the reproductive system and is an important modulator of folliculogenesis, atresia, steroidogenesis, prostaglandin biosynthesis, ovulation, luteolysis, oocyte growth, and maturation. However, there is no report about biological functions and regulatory mechanisms of the NO/cGMP pathway during the follicular formation and development in the neonatal and immature rat. Therefore, my present study uses the histological observation, immunohistochemistry (IHC), RT-PCR, western blot to provide related data. The mainly findings and conclusions are as follows.
1. During postnatal days1,5,7,10, and19, all three isoforms of NOS were mainly localized to the oocytes and expressed as a gradual increase in granulosa cells and theca cells within the growing follicle. The ovarian total NOS activities and NO levels were increased at postnatal days7and10compared with other days. Our findings suggest that the locally produced NO and the NO/cGMP signaling systems are involved in the follicular development before puberty.
2. RT-PCR analysis is to detected the expression and contents of PDEs during the follicle development in the female Sprague-Dawley rats at postnatal days1,5,7,10, and19. The results finds that PDE1A, PDE3A, PDE3B, PDE5A, PDE9A expressed among11kind of cGMP related PDEs. Furthermore, semiquantitative analysis shown that PDE3A and PDE5A are mainly PDEs at different postnatal days and their expression at PND1are lower compared to the other days. And then the expressions are stabilizing. Therefore, our data suggest that PDE3A and PDE5A are involved in the follicular development before puberty by hydrolaseintra-cellular cGMP.
3. We establish the model of inhibition and activation NOS on neonatal and immature rats. The follicular development dynimics have shown that the percentage of antral follicle is markly decreased in the L-NAME+SMT treated group (p<0.05), but increased significantly in the L-Arg group (p<0.01). Moreover, the detection of total NOS, iNOS, eNOS, nNOS have shown that their activities are markly decreased (p<0.05) in the L-NAME+SMT treated group, but increased significantly (p<0.01) in the L-Arg group. However, there are no statistics difference between the single treated with L-NAME or SMT groups and control group. Therefore, our findings suggest that the NOS involved in the follicular development before puberty result and enhance the follicle development.
4. Immunohistochemistry (IHC) and Western Blotting (WB) analysis are used to detect the PI3K/AKT/Foxo3a pathway in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion. The IHC shown that PTEN, AKT and FoxO3a mainly localized in the oocytes at postnatal days5,10, and19, and expressed as a gradual increase in granulosa cells at postnatal day19. Furthermore, WB analysis of the PI3K/AKT/Foxo3a pathway in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion have been used. The expresstion of PTEN is increased and phosphorylatcd AKT and FoxO3a decreased in the L-NAME+SMT treated group at5,10and19days. However, the expresstion of PTEN is decreased and phosphorylated AKT and FoxO3a increased in the L-Arg treated group. But, there are no statistics differences between the single treated with L-NAME or SMT groups and control group. Therefore, our results suggest that NOS involved in the follicular development of neonatal and immature rats through PI3K/AKT/Foxo3a pathway.
5. Immunohistochemistry (IHC) and WB analysis are to detected wheather NOS involved in the follicular development of neonatal and immature rats by autophagy and apoptosis. Our results have shown that Caspase-3(marker of cell apoptosis) and LC3(marker of cell autophagy) are common localized at granulosa cells, oocytes and theca cells. Furthermore, WB analysis of the LC3-Ⅱ and Cleaved-Caspase-3changing in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion. The expresstion of Cleaved-Caspase-3of is increased and LC3-Ⅱ decreased in the L-NAME+SMT treated group at5,10and19days. However, the expression of LC3-Ⅱ is decreased and Cleaved-Caspase-3increased in the L-Arg treated group. But, there are no statistics changing between the single treated with L-NAME or SMT groups and control group. Therefore, our results suggest that NOS involved in the follicular development of neonatal and immature rats by autophagy and apoptosis.
NO/cGMP信号通路在雌性动物生殖生理过程中起着非常广泛的调节作用,诸如介导卵泡闭锁,类固醇,前列腺素的合成,排卵,卵母细胞的生长和成熟卵巢功能等。目前,还没有研究报道NO/cGMP信号通路在新生雌性大鼠卵泡发育过程中的生物学作用及其可能的调控机制。本研究采用组织形态学(HE)、免疫组织化学(IHC)、RT-PCR、免疫印迹(Western blot)等生物化学分子生物学研究技术,全面研究NO/cGMP信号通路在新生雌性大鼠从出生到初情期前卵泡发育过程中的生物学作用和调控机制。其主要发现和结论如下：
1.探讨三种不同的一氧化氮合酶(NOS)亚型在细胞内的表达以及相关的一氧化氮(NO)/环磷酸鸟苷(cGMP)的信号通路在新生和初情期前的雌性大鼠卵巢中的变化。发现,在出生后1天,5,7,10和19天,所有三个亚型的NOS,主要定位于各阶段卵泡的卵母细胞中,并在颗粒细胞和卵泡膜细胞内的增长逐步增加。卵巢总NOS活性和NO水平与其他在产后7日和10日相比,呈显著性增加。与内皮型NOS(eNOS)的,诱导型NOS (iNOS)相比,神经型NOS(nNOS)的活性则保持较低水平。我们的研究结果表明,内源性NOS/cGMP信号系统参与新生雌性大鼠卵泡发育。
2.采用RT-PCR法检测和半定量分析11种cGMP相关磷酸二酯酶在新生雌性大鼠卵巢发育过程中(出生后1,5,7,10,19天)的表达变化。结果发现：只有PDE1A, PDE3A, PDE3B, PDE5A, PDE9A有表达,其它酶类均无表达。进一步的半定量分析,PDE5A, PDE3A是主要表达的酶类。两者在出生后第一天表达较低(p<0.05),但是其余时间点表达稳定,cGMP相关磷酸二酯酶的表达在5天后趋于稳定。这就说明PDE5A, PDE3A参与了新生雌性大鼠卵巢发育并对cGMP起着主要的调控作用。
3.建立体内的一氧化氮合成酶抑制模型,然后组织学观察统计分析不同处理组卵泡发育的动力学变化。我们发现,处理5,10,19天后,L-NAME+SMT处理组,其卵巢中卵泡发育缓慢,在19天时,有腔卵泡数目显著减少(p<0.05),而L-Arg组则呈现提早发育,其有腔卵泡数目显著增加(p<0.01)。进一步检测各处理组总NOS、三种NOS亚型的活性和NO含量,发现,L-NAME+SMT处理组上述指标显著下降(p<0.05),而L-Arg组则显著上升(p<0.01)。但是NOS抑制剂单处理组则与对照差异不显著。研究结果表明NOS参与了新生雌性大鼠的卵巢卵泡发育,并且促进卵泡的提早发育。
4.采用免疫组化、免疫印迹(Western blot)探讨NOS促进卵泡的提早发育的可能机制。免疫组化显示,PI3K/AKT/FoxO3a信号通路主要蛋白PTEN、AKT和FoxO3a在新生雌性大鼠卵泡发育过程中,主要定位于卵母细胞,在出生后19天时,在颗粒细胞也有部分表达,而且其免疫染色增强。进一步的免疫印迹分析,发现：NOS抑制剂L-NAME+SMT处理5,10,19天组,与对照相比,P13K/AKT/FoxO3a信号通路,PTEN表达上升,p-AKT、p-Fox03a表达显著下降。而NOS的底物(L-Arg)处理5,10,19天组,其PI3K/AKT/FoxO3a信号通路激活,即：PTEN表达显著下降,p-AKT、p-FoxO3a表达显著上升。此外,同一处理时间,单注射NOS抑制剂L-NAME或sMT处理组与对照相比则没有显著变化。上述发现说明NOS参与了新生雌性大鼠的卵巢卵泡发育,并且可以通过P13K/AKT/Foxo3a信号通路促进卵泡的提早发育。
5.采用免疫组化、免疫印迹(Western blot)探讨NOS是否通过细胞自噬和凋亡参与新生雌性大鼠卵巢发育。结果发现,凋亡标记蛋白(Caspase-3)和自噬标记蛋白(LC3)在新生大鼠卵巢普遍分布,从出生5天后,主要分布在颗粒细胞,卵母细胞,膜细胞等,进一步的WB检测,NOs抑制剂L-NAME+SMT处理5,10,19天组,与对照相比,LC3-Ⅱ表达下降,Cleaved-caspase-3表达显著上升。而NOS的底物(L-Arg)处理5,10,19天组,其LC3-Ⅱ表达上升,Cleaved-caspase-3表达显著下降。此外,同一处理时间,单注射NOS抑制剂L-NAME或SMT处理组与对照相比则没有显著变化。上述结果证实NOS通过细胞自噬和凋亡参与新生雌性大鼠卵巢发育。
The primordial follicle formation and development in the rat ovary initiates after birth. Originally from egg nests, most follicles go atresia during postnatal days at different developmental stages, the other follicles grow into antral follicles. There are two important phenomenons attract attentions of scientists:1. How the primordial follicle formation from egg nests and grows as antral follicle?2. What impact factors and regulation mechanisms of follicular atresia are contained in the ovary before puberty? The NO/cGMP pathway regulates significantly the biologic and physiologic processes of the reproductive system and is an important modulator of folliculogenesis, atresia, steroidogenesis, prostaglandin biosynthesis, ovulation, luteolysis, oocyte growth, and maturation. However, there is no report about biological functions and regulatory mechanisms of the NO/cGMP pathway during the follicular formation and development in the neonatal and immature rat. Therefore, my present study uses the histological observation, immunohistochemistry (IHC), RT-PCR, western blot to provide related data. The mainly findings and conclusions are as follows.
1. During postnatal days1,5,7,10, and19, all three isoforms of NOS were mainly localized to the oocytes and expressed as a gradual increase in granulosa cells and theca cells within the growing follicle. The ovarian total NOS activities and NO levels were increased at postnatal days7and10compared with other days. Our findings suggest that the locally produced NO and the NO/cGMP signaling systems are involved in the follicular development before puberty.
2. RT-PCR analysis is to detected the expression and contents of PDEs during the follicle development in the female Sprague-Dawley rats at postnatal days1,5,7,10, and19. The results finds that PDE1A, PDE3A, PDE3B, PDE5A, PDE9A expressed among11kind of cGMP related PDEs. Furthermore, semiquantitative analysis shown that PDE3A and PDE5A are mainly PDEs at different postnatal days and their expression at PND1are lower compared to the other days. And then the expressions are stabilizing. Therefore, our data suggest that PDE3A and PDE5A are involved in the follicular development before puberty by hydrolaseintra-cellular cGMP.
3. We establish the model of inhibition and activation NOS on neonatal and immature rats. The follicular development dynimics have shown that the percentage of antral follicle is markly decreased in the L-NAME+SMT treated group (p<0.05), but increased significantly in the L-Arg group (p<0.01). Moreover, the detection of total NOS, iNOS, eNOS, nNOS have shown that their activities are markly decreased (p<0.05) in the L-NAME+SMT treated group, but increased significantly (p<0.01) in the L-Arg group. However, there are no statistics difference between the single treated with L-NAME or SMT groups and control group. Therefore, our findings suggest that the NOS involved in the follicular development before puberty result and enhance the follicle development.
4. Immunohistochemistry (IHC) and Western Blotting (WB) analysis are used to detect the PI3K/AKT/Foxo3a pathway in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion. The IHC shown that PTEN, AKT and FoxO3a mainly localized in the oocytes at postnatal days5,10, and19, and expressed as a gradual increase in granulosa cells at postnatal day19. Furthermore, WB analysis of the PI3K/AKT/Foxo3a pathway in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion have been used. The expresstion of PTEN is increased and phosphorylatcd AKT and FoxO3a decreased in the L-NAME+SMT treated group at5,10and19days. However, the expresstion of PTEN is decreased and phosphorylated AKT and FoxO3a increased in the L-Arg treated group. But, there are no statistics differences between the single treated with L-NAME or SMT groups and control group. Therefore, our results suggest that NOS involved in the follicular development of neonatal and immature rats through PI3K/AKT/Foxo3a pathway.
5. Immunohistochemistry (IHC) and WB analysis are to detected wheather NOS involved in the follicular development of neonatal and immature rats by autophagy and apoptosis. Our results have shown that Caspase-3(marker of cell apoptosis) and LC3(marker of cell autophagy) are common localized at granulosa cells, oocytes and theca cells. Furthermore, WB analysis of the LC3-Ⅱ and Cleaved-Caspase-3changing in the neonatal and immature female rat ovary treated with different NOS inhibition and acitivtion. The expresstion of Cleaved-Caspase-3of is increased and LC3-Ⅱ decreased in the L-NAME+SMT treated group at5,10and19days. However, the expression of LC3-Ⅱ is decreased and Cleaved-Caspase-3increased in the L-Arg treated group. But, there are no statistics changing between the single treated with L-NAME or SMT groups and control group. Therefore, our results suggest that NOS involved in the follicular development of neonatal and immature rats by autophagy and apoptosis.
引文
[1]Nakane M, Schmidt HH, Pollock JS, Forstermann U, Murad F. Cloned human brain nitric oxide synthase is highly expressed in skeletal muscle. [J] FEBS Lett;1993;316:175-80.
[2]Lyons CR, Orloff GJ, Cunningham JM. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. [J] J Biol Chem,1992;267:6370-4.
[3]Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD. Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. [J] J Biol Chem,1992;267:14519-22.
[4]Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. [J] FEBS Lett,1992;307:287-93.
[5]Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. [J] J Biol Chem,1993;268:17478-88.
[6]戴爱国.一氧化氮合酶基因家族研究进展.国外医学生理病理科学与临床分册,1996.
[7]陈晋文,孙长凯,黄远桂.一氧化氮合酶的若干研究进展.生物化学与生物物理进展,1996；23：293-297.
[8]Vodovotz Y, Russell D, Xie QW, Bogdan C, Nathan C. Vesicle membrane association of nitric oxide synthase in primary mouse macrophages. [J] J Immunol,1995;154:2914-25.
[9]Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. [J] J Biol Chem,1994;269: 13725-8.
[10]Masters BS, McMillan K, Sheta EA, Nishimura JS, Roman LJ, Martasek P. Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution:structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO. as a cellular signal. [J] Faseb J,1996; 10:552-8.
[11]Haque MM, Fadlalla M, Wang ZQ, Ray SS, Panda K, Stuehr DJ. Neutralizing a surface charge on the FMN subdomain increases the activity of neuronal nitric-oxide synthase by enhancing the oxygen reactivity of the enzyme heme-nitric oxide complex. [J] J Biol Chem,2009;284:19237-47.
[12]Gorren AC, Mayer B. Tetrahydrobiopterin in nitric oxide synthesis:a novel biological role for pteridines. [J] Curr Drug Metab,2002;3:133-57.
[13]Giovanelli J, Campos KL, Kaufman S. Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine. [J] Proc Natl Acad Sci U S A,1991;88:7091-5.
[14]Schmidt PP, Lange R, Gorren AC, Werner ER, Mayer B, Andersson KK. Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy. [J]J Biol Inorg Chem,2001;6:151-8.
[15]Wei CC, Wang ZQ, Wang Q, Meade AL, Hemann C, Hille R, Stuehr DJ. Rapid kinetic studies link tetrahydrobiopterin radical formation to heme-dioxy reduction and arginine hydroxylation in inducible nitric-oxide synthase. [J] J Biol Chem,2001;276:315-9.
[16]Du M, Yeh HC, Berka V, Wang LH, Tsai AL. Redox properties of human endothelial nitric-oxide synthase oxygenase and reductase domains purified from yeast expression system. [J] J Biol Chem,2003;278:6002-11.
[17]Hemmens B, Goessler W, Schmidt K, Mayer B. Role of bound zinc in dimer stabilization but not enzyme activity of neuronal nitric-oxide synthase. [J] J Biol Chem,2000;275:35786-91.
[18]Hurshman AR, Krebs C, Edmondson DE, Marletta MA. Ability of tetrahydrobiopterin analogues to support catalysis by inducible nitric oxide synthase:formation of a pterin radical is required for enzyme activity. [J] Biochemistry,2003;42:13287-303.
[19]Gorren AC, Kungl AJ, Schmidt K, Werner ER, Mayer B. Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase. [J] Nitric Oxide,2001;5:176-86.
[20]Vogel HJ. The Merck Frosst Award Lecture 1994. Calmodulin:a versatile calcium mediator protein. [J] Biochem Cell Biol,1994;72:357-76.
[21]O'Neil KT, DeGrado WF. How calmodulin binds its targets:sequence independent recognition of amphiphilic alpha-helices. [J] Trends Biochem Sci,1990;15:59-64.
[22]Cho HJ, Xie QW, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. [J] J Exp Med,1992; 176:599-604.
[23]Jones RJ, Smith SM, Gao YT, DeMay BS, Mann KJ, Salerno KM, Salerno JC. The function of the small insertion in the hinge subdomain in the control of constitutive mammalian nitric-oxide synthases. [J] J Biol Chem,2004;279:36876-83.
[24]Roman LJ, Masters BS. Electron transfer by neuronal nitric-oxide synthase is regulated by concerted interaction of calmodulin and two intrinsic regulatory elements. [J] J Biol Chem, 2006;281:23111-8.
[25]Heinzel B, John M, Klatt P, Bohme E, Mayer B. Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. [J] Biochem J,1992;281 (Pt 3):627-30.
[26]Schmidt HH, Smith RM, Nakane M, Murad F. Ca2+/calmodulin-dependent NO synthase type I:a biopteroflavoprotein with Ca2+/calmodulin-independent diaphorase and reductase activities. [J] Biochemistry,1992;31:3243-9.
[27]Abu-Soud HM, Yoho LL, Stuehr DJ. Calmodulin controls neuronal nitric-oxide synthase by a dual mechanism. Activation of intra-and interdomain electron transfer. [J] J Biol Chem,1994;269:32047-50.
[28]Wang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ. Three-dimensional structure of NADPH-cytochrome P450 reductase:prototype for FMN-and FAD-containing enzymes. [J] Proc Natl Acad Sci U S A,1997;94:8411-6.
[29]Garcin ED, Bruns CM, Lloyd SJ, Hosfield DJ, Tiso M, Gachhui R, Stuehr DJ, Tainer JA, Getzoff ED. Structural basis for isozyme-specific regulation of electron transfer in nitric-oxide synthase. [J] J Biol Chem,2004;279:37918-27.
[30]Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases:structure, function and inhibition. [J] Biochem J,2001;357:593-615.
[31]Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. [J] Nature,1991;351: 714-8.
[32]Matsuo R, Misawa K, Ito E. Genomic structure of nitric oxide synthase in the terrestrial slug is highly conserved. [J] Gene,2008;415:74-81.
[33]Klatt P, Schmidt K, Uray G, Mayer B. Multiple catalytic functions of brain nitric oxide synthase. Biochemical characterization, cofactor-requirement, and the role of N omega-hydroxy-L-arginine as an intermediate. [J] J Biol Chem,1993;268:14781-7.
[34]Schulz R, Panas DL, Catena R, Moncada S, Olley PM, Lopaschuk GD. The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. [J] Br J Pharmacol,1995;114:27-34.
[35]张奕华.一氧化氮合酶抑制剂研究进展.药学进展,1997；21：147-151.
[36]Wu CC, Chen SJ, Szabo C, Thiemermann C, Vane JR. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. [J] Br J Pharmacol,1995; 114:1666-72.
[37]Wildhirt SM, Suzuki H, Wolf WP, Dudek R, Horstman D, Weismueller S, Reichart B. S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction. [J] Biochem Biophys Res Commun,1996;227: 328-33.
[38]刘昭前,周宏灏.一氧化氮合酶抑制剂的研究进展.中国药理学通报,1999；15：11-14.
[39]Ignarro LJ, Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide:an overview. [J] Circ Res,2002;90:21-8.
[40]Bryan NS, Bian K, Murad F. Discovery of the nitric oxide signaling pathway and targets for drug development. [J] Front Biosci,2009;14:1-18.
[41]Ignarro LJ. Nitric oxide. [J]Curr Top Med Chem,2005;5:595.
[42]Groneberg D, Konig P, Wirth A, Offermanns S, Koesling D, Friebe A. Smooth muscle-specific deletion of nitric oxide-sensitive guanylyl cyclase is sufficient to induce hypertension in mice. [J] Circulation,2010; 121:401-9.
[43]Koesling D, Friebe A. Soluble guanylyl cyclase:structure and regulation. [J] Rev Physiol Biochem Pharmacol,1999;135:41-65.
[44]Shi F, Stewart RL, Jr., Perez E, Chen JY, LaPolt PS. Cell-specific expression and regulation of soluble guanylyl cyclase alpha 1 and beta 1 subunits in the rat ovary. [J] Biol Reprod,2004;70:1552-61.
[45]Revelli A, Ghigo D, Moffa F, Massobrio M, Tur-Kaspa I. Guanylate cyclase activity and sperm function. [J] Endocr Rev,2002;23:484-94.
[46]Buechler WA, Nakane M, Murad F. Expression of soluble guanylate cyclase activity requires both enzyme subunits. [J] Biochem Biophys Res Commun,1991;174:351-7.
[47]Kimura H, Mittal CK, Murad F. Activation of guanylate cyclase from rat liver and other tissues by sodium azide. [J] J Biol Chem,1975;250:8016-22.
[48]Ignarro LJ, Degnan JN, Baricos WH, Kadowitz PJ, Wolin MS. Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient, heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. [J] Biochim Biophys Acta,1982;718:49-59.
[49]Stone JR, Marletta MA. Soluble guanylate cyclase from bovine lung:activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. [J] Biochemistry,1994;33:5636-40.
[50]Wedel B, Humbert P, Harteneck C, Foerster J, Malkewitz J, Bohme E, Schultz G, Koesling D. Mutation of His-105 in the beta 1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. [J] Proc Natl Acad Sci U S A,1994;91:2592-6.
[51]Katsuki S, Arnold W, Mittal C, Murad F. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. [J] J Cyclic Nucleotide Res,1977;3:23-35.
[52]Denninger JW, Marletta MA. Guanylate cyclase and the.NO/cGMP signaling pathway. [J] Biochim Biophys Acta,1999;1411:334-50.
[53]Zaccolo M, Movsesian MA. cAMP and cGMP signaling cross-talk:role of phosphodiesterases and implications for cardiac pathophysiology. [J] Circ Res,2007;100: 1569-78.
[54]Francis SH, Turko IV, Corbin JD. Cyclic nucleotide phosphodiesterases:relating structure and function. [J] Prog Nucleic Acid Res Mol Biol,2001;65:1-52.
[55]Soderling SH, Beavo JA. Regulation of cAMP and cGMP signaling:new phosphodiesterases and new functions. [J] Curr Opin Cell Biol,2000; 12:174-9.
[56]Omori K, Kotera J. Overview of PDEs and their regulation. [J] Circ Res,2007; 100:309-27.
[57]Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily:a new target for the development of specific therapeutic agents. [J] Pharmacol Ther,2006; 109:366-98.
[58]Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated,3',5'-cyclic nucleotide phosphodiesterases. [J] J Biol Chem,1996;271: 796-806.
[59]Yan C, Bentley JK, Sonnenburg WK, Beavo JA. Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain. [J] J Neurosci,1994; 14: 973-84.
[60]Yu J, Wolda SL, Frazier AL, Florio VA, Martins TJ, Snyder PB, Harris EA, McCaw KN, Farrell CA, Steiner B, Bentley JK, Beavo JA, Ferguson K, Gelinas R. Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1. [J] Cell Signal,1997;9:519-29.
[61]Yan C, Zhao AZ, Bentley JK, Beavo JA. The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner. [J] J Biol Chem,1996;271:25699-706.
[62]Martinez SE, Wu AY, Glavas NA, Tang XB, Turley S, Hol WG, Beavo JA. The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. [J] Proc Natl Acad Sci U S A,2002;99:13260-5.
[63]Sadhu K, Hensley K, Florio VA, Wolda SL. Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. [J] J Histochem Cytochem,1999;47:895-906.
[64]Degerman E, Belfrage P, Manganiello VC. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). [J] J Biol Chem,1997;272:6823-6.
[65]Reinhardt RR, Chin E, Zhou J, Taira M, Murata T, Manganiello VC, Bondy CA. Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. [J] J Clin Invest,1995;95:1528-38.
[66]Corbin JD, Turko IV, Beasley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. [J] Eur J Biochem,2000;267:2760-7.
[67]Yanaka N, Kotera J, Ohtsuka A, Akatsuka H, Imai Y, Michibata H, Fujishige K, Kawai E, Takebayashi S, Okumura K, Omori K. Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. [J] Eur J Biochem,1998;255:391-9.
[68]Kotera J, Fujishige K, Imai Y, Kawai E, Michibata H, Akatsuka H, Yanaka N, Omori K. Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases. [J] Eur J Biochem,1999;262:866-73.
[69]Cote RH. Characteristics of photoreceptor PDE (PDE6):similarities and differences to PDE5. [J] Int J Impot Res,2004;16 Suppl 1:S28-33.
[70]Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. [J] J Biol Chem,1998;273: 15559-64.
[71]Guipponi M, Scott HS, Kudoh J, Kawasaki K, Shibuya K, Shintani A, Asakawa S, Chen H, Lalioti MD, Rossier C, Minoshima S, Shimizu N, Antonarakis SE. Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3:alternative splicing of mRNA transcripts, genomic structure and sequence. [J] Hum Genet,1998;103:386-92.
[72]Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). [J] J Biol Chem,1999;274:18438-45.
[73]Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A:a novel approach to the treatment of psychosis. [J] Neuropharmacology,2006;51: 386-96.
[74]Yuasa K, Kotera J, Fujishige K, Michibata H, Sasaki T, Omori K. Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. [J] J Biol Chem,2000;275:31469-79.
[75]Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Phillips SC. Molecular cloning and characterization of a distinct human phosphodiesterase gene family:PDE11A. [J] Proc Natl Acad Sci USA,2000;97:3702-7.
[76]Hetman JM, Robas N, Baxendale R, Fidock M, Phillips SC, Soderling SH, Beavo JA. Cloning and characterization of two splice variants of human phosphodiesterase 11 A. [J] Proc Natl Acad Sci USA,2000;97:12891-5.
[77]Sharron H. Francis MDH, and Marco Conti. Phosphodiesterase Inhibitors:Factors That Influence Potency, Selectivity, and Action. [M]Handbook of Experimental Pharmacology 2011.
[78]Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. [J]Hum Reprod Update,1998;4:3-24.
[79]Hess KA, Waltz SE, Toney-Earley K, Degen SJ. The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation. [J] Fertil Steril,2003;80 Suppl 2:747-54.
[80]Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. [J] Nature,1990;347:768-70.
[81]Venema RC, Nishida K, Alexander RW, Harrison DG, Murphy TJ. Organization of the bovine gene encoding the endothelial nitric oxide synthase. [J] Biochim Biophys Acta,1994;1218: 413-20.
[82]Tabata M-aHaS. Nitric oxide and ovarian function. [J] Animal Science Journal,2006;77.
[83]Kim H, Moon C, Ahn M, Lee Y, Kim H, Kim S, Ha T, Jee Y, Shin T. Expression of nitric oxide synthase isoforms in the porcine ovary during follicular development. [J] J Vet Sci,2005;6:97-101.
[84]Jablonka-Shariff A, Olson LM. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology,1997;138:460-8.
[85]Van Voorhis BJ, Moore K, Strijbos PJ, Nelson S, Baylis SA, Grzybicki D, Weiner CP. Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. [J] J Clin Invest,1995;96:2719-26.
[86]Zackrisson U, Mikuni M, Wallin A, Delbro D, Hedin L, Brannstrom M. Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. [J] Hum Reprod,1996;11:2667-73.
[87]Bryant CE, Tomlinson A, Mitchell JA, Thiemermann C, Willoughby DA. Nitric oxide synthase in the rat fallopian tube is regulated during the oestrous cycle. [J] J Endocrino,1995;146:149-57.
[88]Zhang W, Wei QW, Wang ZC, Ding W, Wang W, Shi FX. Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovaries of neonatal and immature rats. [J] J Zhejiang Univ Sci B,2011;12:55-64.
[89]Bonavera JJ, Sahu A, Kalra PS, Kalra SP. Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge:involvement of excitatory amino acids. [J] Endocrinology,1993;133:2481-7.
[90]Rettori V, Belova N, Dees WL, Nyberg CL, Gimeno M, McCann SM. Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro. [J] Proc Natl Acad Sci USA,1993;90:10130-4.
[91]Chatterjee S, Collins TJ, Yallampalli C. Inhibition of nitric oxide facilitates LH release from rat pituitaries. [J] Life Sci,1997;61:45-50.
[92]Matsumi H, Koji T, Yano T, Yano N, Tsutsumi O, Momoeda M, Osuga Y, Taketani Y. Evidence for an inverse relationship between apoptosis and inducible nitric oxide synthase expression in rat granulosa cells:a possible role of nitric oxide in ovarian follicle atresia [J] Endocr J,1998;45:745-51.
[93]Faletti A, Perez Martinez S, Perotti C, de Gimeno MA. Activity of ovarian nitric oxide synthase (NOs) during ovulatory process in the rat:relationship with prostaglandins (PGs) production. [J] Nitric Oxide,1999;3:340-7.
[1]Fortune JE, Armstrong DT. Androgen production by theca and granulosa isolated from proestrous rat follicles. [J] Endocrinology,1977;100:1341-7.
[2]McNatty KP, Makris A, DeGrazia C, Osathanondh R, Ryan KJ. The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro. [J] J Clin Endocrinol Metab,1979;49:687-99.
[3]Cohen P, Antoniw JF, Nimmo HG, Yeaman SJ. Protein phosphorylation and hormone action. [J] Ciba Found Symp,1976;41:281-95.
[4]王宁玲.大鼠卵巢原始卵泡形成和发育相关蛋白谱系的构建及功能研究.[D]南京医科大学,2007：p5.
[5]Edwards RG, Fowler RE, Gore-Langton RE, Gosden RG, Jones EC, Readhead C, Steptoe PC. Normal and abnormal follicular growth in mouse, rat and human ovaries. [J] J Reprod Fertil,1977;51:237-63.
[6]McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. [J] Endocr Rev,2000;21:200-14.
[7]Baker TG, Franchi LL. The fine structure of oogonia and oocytes in human ovaries. [J] J Cell Sci,1967;2:213-24.
[8]Sathananthan AH, Selvaraj K, Trounson A. Fine structure of human oogonia in the foetal ovary. [J] Mol Cell Endocrino,12000;161:3-8.
[9]Gondos B. Comparative studies of normal and neoplastic ovarian germ cells:1. Ultrastructure of oogonia and intercellular bridges in the fetal ovary. [J] Int J Gynecol Pathol,1987;6:114-23.
[10]Gondos B. Comparative studies of normal and neoplastic ovarian germ cells:2. Ultrastructure and pathogenesis of dysgerminoma. [J] Int J Gynecol Pathol,1987;6:124-31.
[11]van Wezel IL, Rodgers RJ. Morphological characterization of bovine primordial follicles and their environment in vivo. Biol Reprod 11996;55:1003-11.
[12]Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. [J] Dev Biol,2001;234:339-51.
[13]高辉,郁琦,徐苓.原始卵泡的形成与发育生殖医学杂志.[J]生殖医学杂志,2007；16：253-55.
[14]Pepling ME, Spradling AC. Female mouse germ cells form synchronously dividing cysts. [J] Development,1998; 125:3323-8.
[15]Kezele P, Nilsson EE, Skinner MK. Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. [J] Biol Reprod,2005;73: 967-73.
[16]Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. [J] Mol Hum Reprod,2006;12:61-9.
[17]Holt JE, Jackson A, Roman SD, Aitken RJ, Koopman P, McLaughlin EA. CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary. [J] Dev Biol,2006; 293:449-60.
[18]Nilsson E, Rogers N, Skinner MK. Actions of anti-Mullerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition. [J] Reproduction,2007;134: 209-21.
[19]Dono R, Texido G, Dussel R, Ehmke H, Zeller R. Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. [J] Embo J,1998;17:4213-25.
[20]Dissen GA, Romero C, Paredes A, Ojeda SR. Neurotrophic control of ovarian development. [J] Microsc Res Tech,2002;59:509-15.
[21]Paredes A, Romero C, Dissen GA, DeChiara TM, Reichardt L, Cornea A, Ojeda SR, Xu B. TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. [J] Dev Biol,2004;267:430-49.
[22]Spears N, Molinek MD, Robinson LL, Fulton N, Cameron H, Shimoda K, Telfer EE, Anderson RA, Price DJ. The role of neurotrophin receptors in female germ-cell survival in mouse and human. [J] Development,2003;130:5481-91.
[23]Mazerbourg S, Klein C, Roh J, Kaivo-Oja N, Mottershead DG, Korchynskyi O, Ritvos O, Hsueh AJ. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. [J] Mol Endocrinol,2004;18:653-65.
[24]Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. [J] Nature,1996;383:531-5.
[25]Hayashi M, McGee EA, Min G, Klein C, Rose UM, van Duin M, Hsueh AJ. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. [J] Endocrinology,1999; 140:1236-44.
[26]Aaltonen J, Laitinen MP, Vuojolainen K, Jaatinen R, Horelli-Kuitunen N, Seppa L, Louhio H, Tuuri T, Sjoberg J, Butzow R, Hovata O, Dale L, Ritvos O. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. [J] J Clin Endocrinol Metab,1999;84:2744-50.
[27]Bodensteiner KJ, McNatty KP, Clay CM, Moeller CL, Sawyer HR. Expression of growth and differentiation factor-9 in the ovaries of fetal sheep homozygous or heterozygous for the inverdale prolificacy gene (FecX(Ⅰ)). [J] Biol Reprod,2000;62:1479-85.
[28]Wassarman PM, Albertini, D.F. The mammalian ovum. In:Knobil, E., Neill, J.D. (Eds.), [M] The Physiology of Reproduction.994.
[29]Eppig JJ, Viveiros, M.M., Bivens, C.M., De La Fuente, R. Regulation of mammalian oocyte maturation. In:Leung, P.C., Adashi, E.Y. (Eds.), [M] The Ovary,2004.
[30]Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. [J] Reproduction,2001;122:829-38.
[31]Elvin JA, Matzuk MM. Mouse models of ovarian failure. [J] Rev Reprod,1998;3:183-95.
[32]Soyal SM, Amleh A, Dean J. FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. [J] Development,2000;127:4645-54.
[33]Castrillon DH, Miao L, Kollipara R, Homer JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. [J] Science,2003;301:215-8.
[34]Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. [J] Science,2004;305:1157-9.
[35]Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, Treier M. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. [J] Developmen,2004;131:933-42.
[36]Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, Matzuk MM, Rajkovic A. Oogenesis requires germ cell-specific transcriptional regulators Sohlhl and Lhx8. [J] Proc Natl Acad Sci U SA,2006;103:8090-5.
[37]Albertini DF, Barrett SL. Oocyte-somatic cell communication. [J] Reprod Suppl,2003;61: 49-54.
[38]Shimasaki S, Moore RK, Otsuka F, Erickson GF. The bone morphogenetic protein system in mammalian reproduction. [J] Endocr Rev,2004;25:72-101.
[39]Vanderhyden B. Molecular basis of ovarian development and function. [J] Front Biosci,2002;7:d2006-22.
[40]Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. [J] Proc Natl Acad Sci U S A,2002;99:2890-4.
[41]Hashimoto O, Moore RK, Shimasaki S. Posttranslational processing of mouse and human BMP-15:potential implication in the determination of ovulation quota. [J] Proc Natl Acad Sci U S A,2005; 102:5426-31.
[42]Thomas FH, Ethier JF, Shimasaki S, Vanderhyden BC. Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors. [J] Endocrinology,2005;146:941-9.
[43]Albertini DF, Combelles CM, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. [J] Reproduction,2001;121:647-53.
[44]Kidder GM, Mhawi AA. Gap junctions and ovarian folliculogenesis. [J] Reproduction,2002;123:613-20.
[45]Vanhaesebroeck B, Alessi DR. The PI3K-PDK1 connection:more than just a road to PKB. [J] Biochem J,2000;346 Pt 3:561-76.
[46]Weigel D, Jurgens G, Kuttner F, Seifert E, Jackle H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. [J] Cell,1989;57:645-58.
[47]Ronnebaum SM, Patterson C. The FoxO family in cardiac function and dysfunction. [J] Annu Rev Physiol,2010,72:81-94.
[48]Zhang X, Rielland M, Yalcin S, Ghaffari S. Regulation and function of FoxO transcription factors in normal and cancer stem cells:what have we learned? [J] Curr Drug Targets,2011; 12:1267-83.
[49]Shi F, LaPolt PS. Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary. [J] J Endocrinol,2003; 179:195-203.
[50]李学斌,谢庄,石放雄.FOXO蛋白的修饰和细胞凋亡和癌变.[J]生物化学和生物物理进展,2005；32：600-06.
[51]Khan J, Bittner ML, Saal LH, Teichmann U, Azorsa DO, Gooden GC, Pavan WJ, Trent JM, Meltzer PS. cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. [J] Proc Natl Acad Sci U S A,1999;96:13264-9.
[52]Yamamura Y, Lee WL, Inoue K, Ida H, Ito Y. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. [J] J Biol Chem,2006;281:5267-76.
[53]隋旭霞,罗丽莉,傅玉才.新生鼠卵巢FOXO3a表达水平与卵母细胞凋亡的相关性初步研.[J]生殖与避孕,2006；26：515-19.
[54]隋旭霞,傅玉才,罗丽莉.Foxo3a转录因子参与卵母细胞的凋亡.[J]中国现代医学杂志,2007；17：1438-41.
[55]Leslie NR, Downes CP. PTEN:The down side of PI 3-kinase signalling. [J] Cell Signal,2002;14:285-95.
[56]Sulis ML, Parsons R. PTEN:from pathology to biology. [J] Trends Cell Biol,2003;13: 478-83.
[57]Parsons R. Human cancer, PTEN and the PI-3 kinase pathway. [J] Semin Cell Dev Biol,2004;15:171-6.
[58]Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, Du C, Tang W, Hamalainen T, Peng SL, Lan ZJ, Cooney AJ, Huhtaniemi I, Liu K. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. [J] Science,2008;319: 611-3.
[59]John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. [J] Dev Biol,2008;321:197-204.
[60]Liu K, Rajareddy S, Liu L, Jagarlamudi K, Boman K, Selstam G, Reddy P. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway:new roles for an old timer. [J] Dev Biol,2006;299:1-11.
[61]TABATA M-aHaS. Nitric oxide and ovarian function. [J] Animal Science Journal,2006;77.
[62]Van Voorhis BJ, Dunn MS, Snyder GD, Weiner CP. Nitric oxide:an autocrine regulator of human granulosa-luteal cell steroidogenesis. [J] Endocrinology,1994;135:1799-806.
[63]Jablonka-Shariff A, Olson LM. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology,1997;138:460-8.
[64]Van Voorhis BJ, Moore K, Strijbos PJ, Nelson S, Baylis SA, Grzybicki D, Weiner CP. Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. [J] J Clin Invest,1995;96:2719-26.
[65]Zackrisson U, Mikuni M, Wallin A, Delbro D, Hedin L, Brannstrom M. Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. [J] Hum Reprod,1996;11:2667-73.
[66]Takesue K, Hattori MA, Nishida N, Kato Y, Fujihara N. Expression of endothelial nitric oxide synthase gene in cultured porcine granulosa cells after FSH stimulation. [J] J Mol Endocrinol,2001;26:259-65.
[67]Shi F, Stewart RL, Jr., Perez E, Chen JY, LaPolt PS. Cell-specific expression and regulation of soluble guanylyl cyclase alpha 1 and beta 1 subunits in the rat ovary. Biol Reprod,2004;70: 1552-61.
[68]Gregg AR. Mouse models and the role of nitric oxide in reproduction. [J] Curr Pharm Des,2003;9:391-8.
[69]Jablonka-Shariff A, Ravi S, Beltsos AN, Murphy LL, Olson LM. Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice. [J] Biol Reprod,1999;61:171-7.
[70]Pallares P, Garcia-Fernandez RA, Criado LM, Letelier CA, Esteban D, Fernandez-Toro JM, Flores JM, Gonzalez-Bulnes A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008;136:573-9.
[71]Gregg AR, Schauer A, Shi O, Liu Z, Lee CG, O'Brien WE. Limb reduction defects in endothelial nitric oxide synthase-deficient mice. [J] Am J Physiol,1998;275:H2319-24.
[72]Jablonka-Shariff A, Olson LM. The role of nitric oxide in oocyte meiotic maturation and ovulation:meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. [J] Endocrinology,1998; 139:2944-54.
[73]Hefler LA, Gregg AR. Inducible and endothelial nitric oxide synthase:genetic background affects ovulation in mice. [J] Fertil Steril,2002;77:147-51.
[74]Gyurko R, Leupen S, Huang PL. Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in hypogonadism and infertility. [J] Endocrinology,2002;143:2767-74.
[75]Tsutsui M, Shimokawa H, Morishita T, Nakashima Y, Yanagihara N. Development of genetically engineered mice lacking all three nitric oxide synthases. [J] J Pharmacol Sci,2006;102:147-54.
[76]Zhang W, Wei QW, Wang ZC, Ding W, Wang W, Shi FX. Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovaries of neonatal and immature rats. [J] J Zhejiang Univ Sci B,2011;12:55-64.
[77]LaPolt PS, Leung K, Ishimaru R, Tafoya MA, You-hsin Chen J. Roles of cyclic GMP in modulating ovarian functions. [J] Reprod Biomed Online,2003;6:15-23.
[78]Ishimaru RS, Leung K, Hong L, LaPolt PS. Inhibitory effects of nitric oxide on estrogen production and cAMP levels in rat granulosa cell cultures. [J] J Endocrinol,2001;168:249-55.
[79]Grasselli F, Ponderato N, Basini G, Tamanini C. Nitric oxide synthase expression and nitric oxide/cyclic GMP pathway in swine granulosa cells. [J] Domest Anim Endocrinol,2001;20: 241-52.
[80]Engels K, Knauer SK, Loibl S, Fetz V, Harter P, Schweitzer A, Fisseler-Eckhoff A, Kommoss F, Hanker L, Nekljudova V, Hermanns I, Kleinert H, Mann W, du Bois A, Stauber RH. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. [J] Cancer Res,2008;68:5159-66.
[81]Borniquel S, Garcia-Quintans N, Valle I, Olmos Y, Wild B, Martinez-Granero F, Soria E, Lamas S, Monsalve M. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration. [J] Mol Cell Biol,2010;30: 4035-44.
[1]Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.[J] Br J Cancer,1972;26:239-57.
[2]Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. [J] Blood,2001;98:2603-14.
[3]刘光伟龚守良.细胞凋亡信号传导途径的研究进展.[J]吉林大学学报(医学版),2004；30：485-88.
[4]Hotchkiss RS. Cell Death. [J] N Engl J Med,2009;361:1570-83.
[5]戴昕,李占全,冀林华.凋亡相关蛋白Caspase研究进展.[J]中国现代医药杂志,2010；12：130-32.
[6]Villa P KS, Earnshaw WC. Caspases and caspase inhibitors. [J] TIBS,1997;22.
[7]Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. [J] J Biol Chem,1994;269:30761-4.
[8]Nicholson DW, Thornberry NA. Caspases:killer proteases. [J] Trends Biochem Sci,1997;22: 299-306.
[9]Hishikawa K, Nakaki T, Fujii T. Connective tissue growth factor induces apoptosis via caspase 3 in cultured human aortic smooth muscle cells. [J] Eur J Pharmacol,2000;392: 19-22.
[10]Buckley CD, Pilling D, Henriquez NV, Parsonage G, Threlfall K, Scheel-Toellner D, Simmons DL, Akbar AN, Lord JM, Salmon M. RGD peptides induce apoptosis by direct caspase-3 activation. [J] Nature,1999;397:534-9.
[11]Pru JK TJ. Programmed cell death in the ovary:insights and future prospects using genetic technologies. [J] Mol Endocrinol,2001; 15:845-53.
[12]He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. [J] Annu Rev Genet,2009;43:67-93.
[13]Glick D, Barth S, Macleod KF. Autophagy:cellular and molecular mechanisms. [J] J Pathol,2010; 221:3-12.
[14]Mehrpour M, Esclatine A, Beau I, Codogno P. Overview of macroautophagy regulation in mammalian cells. [J] Cell Res,2010; 20:748-62.
[15]Puyal J, Ginet V, Grishchuk Y, Truttmann AC, Clarke PG Neuronal Autophagy as a Mediator of Life and Death:Contrasting Roles in Chronic Neurodegenerative and Acute Neural Disorders. [J] Neuroscientist,2011.
[16]Yang Z, Klionsky DJ. Mammalian autophagy:core molecular machinery and signaling regulation. [J] Curr Opin Cell Biol,2010;22:124-31.
[17]Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. [J] Mol Biol Cell,2009;20:1981-91.
[18]Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. [J]Mol Biol Cell,2009;20:1992-2003.
[19]Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. [J] Mol Biol Cell,2008;19: 5360-72.
[20]Liang C, Sir D, Lee S, Ou JH, Jung JU. Beyond autophagy:the role of UVRAG in membrane trafficking. [J] Autophagy,2008;4:817-20.
[21]Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. [J] Proc Natl Acad Sci U S A,2008;105:19211-6.
[22]Longatti A, Tooze SA. Vesicular trafficking and autophagosome formation. [J]Cell Death Differ,2009; 16:956-65.
[23]Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. [J] J Cell Sci,2003;116: 1679-88.
[24]Nakatogawa H, Ichimura Y, Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. [J] Cell,2007; 130: 165-78.
[25]Wu Y, Li X, Zhu JX, Xie W, Le W, Fan Z, Jankovic J, Pan T. Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease. [J] Neurosignals,2011; 19:163-74.
[26]Yang DS, Kumar A, Stavrides P, Peterson J, Peterhoff CM, Pawlik M, Levy E, Cataldo AM, Nixon RA. Neuronal apoptosis and autophagy cross talk in aging PS/APP mice, a model of Alzheimer's disease. [J] Am J Pathol,2008;173:665-81.
[27]Gonzalez-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquere S, Eskelinen EL, Pierron G, Saftig P, Kroemer G. The apoptosis/autophagy paradox:autophagic vacuolization before apoptotic death. [J] J Cell Sci,2005;118:3091-102.
[28]Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. [J] Oncogene,2008;27:6434-51.
[29]Peri P, Nuutila K, Vuorinen T, Saukko P, Hukkanen V. Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells. [J] J Gen Virol,2010; 92:173-80.
[30]Almaguel FG, Liu JW, Pacheco FJ, De Leon D, Casiano CA, De Leon M. Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane permeabilization and cathepsin L activity. [J] Brain Res,2010; 1318:133-43.
[31]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury:a role of autophagy. [J] Acta Pharmacol Sin,2011; 32:1089-99.
[32]Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G. Inhibition of macroautophagy triggers apoptosis. [J] Mol Cell Biol,2005;25:1025-40.
[33]Galluzzi L, Vicencio JM, Kepp O, Tasdemir E, Maiuri MC, Kroemer G. To die or not to die: that is the autophagic question. [J] Curr Mol Med,2008;8:78-91.
[34]Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Sato S, Ishikawa K, Imoto M, Hattori N. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. [J] Autophagy,2011;7:176-87.
[35]Gawriluk TR, Hale AN, Flaws JA, Dillon CP, Green DR, Rucker EB,3rd. Autophagy is a cell survival program for female germ cells in the murine ovary. [J] Reproduction,2011;141: 759-65.
[36]Clarke PG Developmental cell death:morphological diversity and multiple mechanisms. [J] Anat Embryol (Berl),1990;181:195-213.
[37]Baehrecke EH. How death shapes life during development. [J] Nat Rev Mol Cell Biol,2002;3: 779-87.
[38]Ortiz R, Echeverria OM, Salgado R, Escobar ML, Vazquez-Nin GH. Fine structural and cytochemical analysis of the processes of cell death of oocytes in atretic follicles in new born and prepubertal rats. [J] Apoptosis,2006;11:25-37.
[39]Escobar ML, Echeverria OM, Ortiz R, Vazquez-Nin GH. Combined apoptosis and autophagy, the process that eliminates the oocytes of atretic follicles in immature rats. [J] Apoptosis,2008;13:1253-66.
[40]Escobar ML, Echeverria OM, Sanchez-Sanchez L, Mendez C, Pedernera E, Vazquez-Nin GH. Analysis of different cell death processes of prepubertal rat oocytes in vitro. [J] Apoptosis, 2010; 15:511-26.
[41]Pritchett TL, Tanner EA, McCall K. Cracking open cell death in the Drosophila ovary. [J] Apoptosis,2009;14:969-79.
[42]Tingen C, Kim A, Woodruff TK. The primordial pool of follicles and nest breakdown in mammalian ovaries. [J] Mol Hum Reprod,2009;15:795-803.
[43]Tingen CM, Bristol-Gould SK, Kiesewetter SE, Wellington JT, Shea L, Woodruff TK. Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. [J] Biol Reprod,2009;81:16-25.
[44]Lobascio AM, Klinger FG, Scaldaferri ML, Farini D, De Felici M. Analysis of programmed cell death in mouse fetal oocytes. [J] Reproduction,2007;134:241-52.
[45]Choi J, Jo M, Lee E, Choi D. Induction of apoptotic cell death via accumulation of autophagosomes in rat granulosa cells. [J] Fertil Steril,2011; 95:1482-6.
[46]Choi JY, Jo MW, Lee EY, Yoon BK, Choi DS. The role of autophagy in follicular development and atresia in rat granulosa cells. [J] Fertil Steril,2011;93:2532-7.
[47]Basini G, Grasselli F, Ponderato N, Bussolati S, Tamanini C. Lipid hydroperoxide and cGMP are not involved in nitric oxide inhibition of steroidogenesis in bovine granulosa cells. [J] Reprod Fertil Dev 12000; 12:289-95.
[48]Basini G, Baratta M, Ponderato N, Bussolati S, Tamanini C. Is nitric oxide an autocrine modulator of bovine granulosa cell function? [J] Reprod Fertil Dev,1998; 10:471-8.
[49]Pawan K. Dubey VT, Ram Pratap Singh, K.V.H. Sastry, G. Taru Sharma Influence of nitric oxide on steroid synthesis, growth and apoptosis of Buffalo granulosa cells in vitro. [J] J. Anim. Sci,2011;24:1204-10.
[50]Matsumi H, Yano T, Osuga Y, Kugu K, Tang X, Xu JP, Yano N, Kurashima Y, Ogura T, Tsutsumi O, Koji T, Esumi H, Taketani Y. Regulation of nitric oxide synthase to promote cytostasis in ovarian follicular development. [J] Biol Reprod,2000;63:141-6.
[51]Yoon SJ, Choi KH, Lee KA. Nitric oxide-mediated inhibition of follicular apoptosis is associated with HSP70 induction and Bax suppression. [J] Mol Reprod Dev,2002;61:504-10.
[52]Chun SY, Eisenhauer KM, Kubo M, Hsueh AJ. Interleukin-1 beta suppresses apoptosis in rat ovarian follicles by increasing nitric oxide production. Endocrinology,1995; 136:3120-7.
[53]Chu HP, Etgen AM. Ovarian hormone dependence of alpha(1)-adrenoceptor activation of the nitric oxide-cGMP pathway:relevance for hormonal facilitation of lordosis behavior. [J] J Neurosci,1999;19:7191-7.
[54]Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J, Wada O, Koga K, Fujiwara T, Kugu K, Taketani Y. Cross-Talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis:a possible regulatory mechanism for ovarian follicle atresia. [J] Endocrinology,2005; 146:808-15.
[55]Preutthipan S, Chen SH, Tilly JL, Kugu K, Lareu RR, Dharmarajan AM. Inhibition of nitric oxide synthesis potentiates apoptosis in the rabbit corpus luteum. [J] Reprod Biomed Online,2004;9:264-70.
[56]Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O'Kane CJ, Rubinsztein DC. Complex inhibitory effects of nitric oxide on autophagy. [J] Mol Cell,2011;43:19-32.
[57]Rabkin SW, Klassen SS. Nitric oxide differentially regulates the gene expression of caspase genes but not some autophagic genes. [J] Nitric Oxide,2007;16:339-47.
[58]Rabkin SW. Nitric oxide-induced cell death in the heart:the role of autophagy. [J],2007;3: 347-9.
[1]Rosselli, M., Keller, P.J., Dubey, R.K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. [J] Hum. Reprod. Update,2008; 4:3-24.
[2]Griffith, O.W., Stuehr, D.J. Nitric oxide synthase properties and catalytic mechanism. [J] Annu. Rev. Physiol.,1995; 57:707-736.
[3]Snyder, S.H. Nitric oxide:NO endothelial NO. [J] Nature,1995; 377:196-197.
[4]Nathan, C., Xie, Q.W. Regulation of biosynthesis of nitric oxide. [J] J. Biol. Chem.,1994; 269:13725-13728.
[5]Hattori, M.A., Tabata, S. Nitric oxide and ovarian function. [J] Anim. Sci. J.,2006; 77:275-284.
[6]Kim, H., Moon, C., Ahn, M., Lee, Y., Kim, S., Ha, T., Jee, Y.,Shin, T. Expression of nitric oxide synthase isoforms in the porcine ovary during follicular development. [J] J. Vet. Sci., 2005; 6:97-101.
[7]Olson, L.M., Jones-Burton, C.M., Jablonka-Shariff, A. Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells:possible role for nitric oxide in functional luteal regression. [J] Endocrinology,1996; 137:3531-3539.
[8]Srivastava, V., Jones, B.J., Dookwah, H., Hiney, J.K., Dees, W.L. Ovarian nitric oxide synthase (NOS) gene expression during peripubertal development. [J] Life Sci.,1997; 61:1507-1516.
[9]Mitchell, L.M., Kennedy, C.R., Hartshorne, G.M. Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles. [J] Hum. Reprod.,2004;19:30-40.
[10]Arnold, W.P., Aldred, R., Murad, F. Cigarette smoke activates guanylate cyclase and increases guanosine3',5'-monophosphate in tissues. [J] Science,1977; 198:934-936.
[11]Nakamura, Y., Yamagata, Y., Sugino, N., Takayama, H., Kato,H. Nitric oxide inhibits oocyte meiotic maturation.Biol. [J] Reprod.,2002; 67:1588-1592.
[12]Chen, Y.H., Tafoya, M., Ngo, A., LaPolt, P.S. Effects of nitric oxide and cGMP on inhibin A and inhibin subunit mRNA levels from cultured rat granulosa cells. [J] Fertil.Steril.,2003; 79:687-693.
[13]Palmer, R.M., Moncada, S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem. Biophys. Res. [J] Commun.,1989; 158:348-352.
[14]Moncada, S., Palmer, R.M., Higgs, E.A. Nitric oxide:physiology, pathophysiology, and pharmacology. [J] Pharmacol. Rev.,1991; 43:109-142.
[15]Lewis, R.S., Deen, W.M. Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. [J] Chem. Res.Toxicol.,1994; 7:568-574
[16]Theilig, F., Bostanjoglo, M., Pavenstadt, H., Grupp, C.,Holland, G., Slosarek, I., Gressner, A.M., Russwurm, M., Koesling, D., Bachmann, S. Cellular distribution and function of soluble guanylyl cyclase in rat kidney and liver. [J] J. Am. Soc. Nephrol.,2001; 12:2209-2220.
[17]Sette, C., Conti, M. Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. [J] J. Biol. Chem.,1996; 271:16526-16534.
[18]Nichols, M.R., Morimoto, B.H. Differential inhibition of multiple cAMP phosphodiesterase isozymes by isoflavones and tyrphostins. [J] Mol. Pharmacol.,2000; 57:738-745.
[19]Tamanini, C.G.B., Grasselli, F., Tirelli, M. Nitric oxide and the ovary. [J] J. Anim. Sci.,2003; 81:E1-E7.
[20]Matsumi, H., Yano, T., Koji, T., Ogura, T., Tsutsumi, O.,Taketani, Y., Esumi, H. Expression and localization of inducible nitric oxide synthase in the rat ovary:a possible involvement of nitric oxide in the follicular development. Biochem. Biophys. [J] Res. Commun.,1998; 243:67-72.
[21]van den Hurk, R., Zhao, J. Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. [J] Theriogenology,2005; 63:1717-1751.
[22]Drazen, D.L., Klein, S.L., Burnett, A.L., Wallach, E.E., Crone,J.K., Huang, P.L., Nelson, R.J. Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase. [J] Nitric. Oxide,1999; 3:366-374.
[23]Jablonka-Shariff, A., Olson, L.M. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology, 1997; 138:460-468.
[24]Pallares, P., Garcia-Fernandez, R.A., Criado, L.M., Letelier, C.A., Esteban, D., Fernandez-Toro, J.M., Flores, J.M., Gonzalez-Bulnes, A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008; 136:573-579.
[25]Wang, Z., Shi, F., Jiang, Y.Q., Lu, L.Z., Wang, H., Watanabe,G., Taya, K. Changes of cyclic AMP levels and phosphodiesterase activities in the rat ovary. [J] J. Reprod.Dev.,2007; 53:717-725.
[26]Lamprecht, S.A., Zor, U., Tsafriri, A., Lindner, H.R. Action of prostaglandin E 2 and of luteinizing hormone on ovarian adenylate cyclase, protein kinase and ornithine decarboxylase activity during postnatal development and maturity in the rat. [J] J. Endocrinol,1987; 57:217-233.
[27]Sokka, T., Huhtaniemi, I. Ontogeny of gonadotrophin receptors and gonadotrophin-stimulated cyclic AMP production in the neonatal rat ovary. [J] J. Endocrinol.,1990;127:297-303.
[28]Jablonka-Shariff, A., Ravi, S., Beltsos, A.N., Murphy, L.L.,Olson, L.M. Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice. [J] Biol. Reprod.,1999; 61:171-177.
[29]Huang, J., Roby, K.F., Pace, J.L., Russell, S.W., Hunt, J.S. Cellular localization and hormonal regulation of inducible nitric oxide synthase in cycling mouse uterus. [J] J.Leukoc. Biol.,1995; 57:27-35.
[30]McGee, E., Spears, N., Minami, S., Hsu, S.Y., Chun, S.Y.,Billig, H., Hsueh, A.J. Preantral ovarian follicles in serum-free culture:suppression of apoptosis after activation of the cyclic guanosine 3',5'-monophosphate pathway and stimulation of growth and differentiation by follicle-stimulating hormone. [J] Endocrinology,1997; 138:2417-2424.
[31]Shi, F., Stewart, R.L.Jr., Perez, E., Chen, J.Y., LaPolt, P.S. Cell-specific expression and regulation of soluble guanylyl cyclase α1 and β1 subunits in the rat ovary. [J] Biol.Reprod., 2004; 70:1552-1561.
[32]Lancaster, J.R.Jr. A tutorial on the diffusibility and reactivity of free nitric oxide. [J] Nitric. Oxide,1997; 1:18-30.
[33]Kelm, M. Nitric oxide metabolism and breakdown.Biochim. [J] Biophys. Acta,1999; 1411:273-289.
[1]LaPolt PS, Leung K, Ishimaru R, et al. Roles of cyclic GMP in modulating ovarian functions. [J] Reprod Biomed Online,2003; 6:15-23
[2]Mehats C, Andersen CB, Filopanti M, et al. Cyclic nucleotide phosphodiesterases and their role in endocrine cell signalling.[J] Trends Endocrinol Metab.,2002;13:29-35.
[4]Uckert S, Hedlund P, Andersson KE, et al.Update on Phosphodiesterase (PDE) Isoenzymes as Pharmacologic Targets in Urology:Present and Future.[J] Eur Urol.,2006; 50:1194-1207
[3]Francis SH, Turko IV, Corbin JD. Cyclic nucleotide phosphodiesterases:relating structure and function. Prog. [J] Nucleic Acid Res. Mol. Biol.2001; 65:1-52
[5]Masciarelli S, Horner K, Liu C,et al. Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. [J] J Clin Invest.2004; 114:196-205
[6]Effect of Type 3 and Type 4 Phosphodiesterase Inhibitors on the Maintenance of Bovine Oocytes in Meiotic Arrest. [J] Biol Reprod.2002; 66,180-184.
[7]Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. [J] The EMBO Journal,2006; 25:5716-5725
[8]Wei Zhang, Quanwei Wei, Zhengchao Wang, Wei Ding, Wei Wang, Fangxiong Shi, Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovary of neonatal and immature rats. [J] J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2011; 12:55-64
[9]Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. [J] Journal of Hepatology,2006; 44:886-893
[10]Expression and activity of cGMP-dependent phosphodiesterases is up-regulated by lipopolysaccharide (LPS) in rat peritoneal macrophages. [J] Biochimica et Biophysica Acta, 2007;1773:209-218
[11]Overview of PDEs and Their Regulation. [J]Circ Res.2007; 100:309-327
[12]LUGN IER C. Cyclic nucleotide phosphodiesterase (PDE) superfarmily:A new targe t for the development of specif ic the rapeutic agents [J]. Pharmacol Ther,2006; 109:366-398.
[13]Degerman E, Belfrage P, Manganiello VC. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). [J] J Biol Chem.1997; 272:6823-6826.
[14]Cloning and characterization of the cyclic guanosine monophosphate-inhibited phosphodiesterase PDE3A Expressed in mouse oocyte. [J] Biol Reprod.,2001; 65:188-196
[15]Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes. [J] Biol Reprod.,2009; 81:595-604
[16]Wang Z, Shi F, Jiang Y, Lu L, Watanabe G, Taya K. Changes of cyclic AMP levels and phosphodiesterase activities in the rat ovary. [J] J Reprod Dev.,2007; 53,717-725.
[17]Corbin JD, Turko IV, Beasley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. [J] Eur J Biochem.2000; 267:2760-2767.
[18]Sasseville, M., Guillemette, C., Coulombe, Z., Richard, F.,2005. Detection and potential role of 3'-5'cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5A (PDE5A) in porcine ovary. [J] Fertil. Steril.2005; 84 (s1):397
[19]Donato MA, Saraiva KL, Soares e Silva AK, Wanderley MI, Peixoto CA. Follicle development and luteal cell morphology altered by phosphodiesterase-5 inhibitor. [J] Micron. 2009; 40:845-50.
[20]Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. [J] J Biol Chem.1998; 273:15559 -155564.
[21]Guipponi M, Scott HS, Kudoh J et al. Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3:alternative splicing of mRNA transcripts, genomic structure and sequence. [J] Hum Genet.1998; 103:386-392.
[22]Rentero C, Monfort A, Puigdomenech P. Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene. [J] Biochem Biophys Res Commun,2003; 301:686-692
[23]Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated,3-,5--cyclic nucleotide phosphodiesterases. [J] J Biol Chem.1996; 271:796-806.
[1]Rosselli M, Keller, P. J., Dubey, R. K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum.[J] Reprod. Update.,1998; 4:3-24.
[2]Tabata, M-aHaS. Nitric oxide and ovarian function. [J] Animal. Science. Journal., 2006;77:275-284.
[3]Pallares, P., Garcia-Fernandez, R.A., Criado, L.M., Letelier, C.A., Esteban, D., Fernandez-Toro, J.M., Flores, J.M., Gonzalez-Bulnes, A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J]Reproduction,2008; 136:573-579.
[4]Jablonka-Shariff A, Ravi S, Beltsos AN, Murphy LL, Olson LM. Abnormal Estrous Cyclicity after Disruption of Endothelial and Inducible Nitric Oxide Synthase in Mice. [J] Biol Reprod. 1999; 61,171-177.
[5]Gregg AR, Schauer A, Shi O, Liu Z, Lee CG, O'Brien WE.Limb reduction defects in endothelial nitric oxide synthase-deficient mice. [J] Am J Physiol.1998; 275:2319-2324.
[6]Pallares P, Garcia-Fernandez RA, Criado LM, Letelier CA, Esteban D, Fernandez-Toro JM, Flores JM, Gonzalez-Bulnes A.Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008; 136:573-579.
[7]Jablonka-Shariff A, Olson LM. The Role of Nitric Oxide in Oocyte Meiotic Maturation and Ovulation:Meiotic Abnormalities of Endothelial Nitric Oxide Synthase Knock-Out Mouse Oocytes. [J] Endocrinology,1998; 139:2944-2954.
[8]Hefler LA, Gregg AR. Inducible and endothelial nitric oxide synthase:genetic background affects ovulation in mice. [J] Fertil Steril.2002; 77(1):147-51.
[9]Gyurko R, Leupen S, Huang PL.Deletion of Exon 6 of the Neuronal Nitric Oxide Synthase Gene in Mice Results in Hypogonadism and Infertility. [J] Endocrinology,2002; 143: 2767-2774.
[10]Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases [J] J Pharmacol Sci,2006; 102:147-154.
[11]Wei Zhang, Quanwei Wei, Zhengchao Wang, Wei Ding, Wei Wang, Fangxiong Shi, Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovary of neonatal and immature rats. [J]J Zhejiang Univ-Sci B (Biomed & Biotechnol),2011;12:55-64.
[12]Shukovski L, Tsafriri A, The involvement of Nitric Oxide in the ovulatory process in the rat. [J]Endocrinology.1994; 135:2287-90.
[13]Effects of L-NAME and L-Arg on meiotic maturation ofmouse oocyte in vivo. [J] Journal of agricultural biotechnology,2003;11:291-294
[14]Flaws JA, Abbud R, Mann RJ, Nilson JH, Hirshfield AN. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. [J Biol Reprod,1997; 57:1233-1237.
[15]Vitt UA, McGee EA, Hayashi M, Hsueh AJ. In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. [J] Endocrinology.2000; 141:3814-20.
[16]Schulz R, Panas DL, Catena R, Moncada S, Olley PM, Lopaschuk GD. The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. [J] Br J Pharmacol,1995;114:27-34.
[17]Wassarman PM, Albertini, D.F. The mammalian ovum. In:Knobil, E., Neill, J.D. (Eds.), [M] The Physiology of Reproduction.994.
[18]Elvin JA, Matzuk MM. Mouse models of ovarian failure. [J] Rev Reprod,1998; 3:183-95.
[19]Shi F, Stewart R L, Pere E, Chen JY, LaPolt PS Cell-specific expression and regulation of soluble guanylyl cyclase alpha and beta subunit in the rat ovary. [J] Bio Reprod,2004; 70: 1552-1561.
[20]Castrillon DH, Miao L1, Kollipara R, James WH, Ronald AD. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. [J]Science,2003; 301:215-218.
[21]John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. [J] Dev Biol,2008; 321:197-204.
[22]Engels K, Knauer SK, Loibl S, Fetz V, Harter P, Schweitzer A, Fisseler-Eckhoff A, Kommoss F, Hanker L, Nekljudova V, Hermanns I, Kleinert H, Mann W, du Bois A, Stauber RH. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. [J] Cancer Res,2008; 68:5159-66.
[23]Borniquel S, Garcia-Quintans N, Valle I, Olmos Y, Wild B, Martinez-Granero F, Soria E, Lamas S, Monsalve M. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration. [J] Mol Cell Biol,2010; 30: 4035-44.
[24]Kim YM, Bombeck CA, Billiar TR. Nitric Oxide as a Bifunctional Regulator of Apoptosis. [J]Circ Res.1999; 19; 84:253-6.
[25]Chun SY, Hsueh AJ.Paracrine mechanisms of ovarian follicle apoptosis. [J] J Reprod Immunol. 1998; 39:63-75.
[1]Cantley LC. The phosphoinositide 3-kinase pathway [J]. Science,2002,296:1655-1657
[2]Cully M, You H, Levine AJ, et al. Beyond PTEN mutations:the PI3K pathway as an integrator of multiple inputs during tumorigenesis [J]. Nat Rev Cancer,2006,6:184-192
[3]Tran H, Brunet A, Griffith EC, et al. The many forks in FOXO's road [J]. Sci STKE 2003,172: re5
[4]Castrillon DH, Miao L1, Kollipara R, et al. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a[J]. Science,2003,301:215-218
[5]Liu K, Raja reddy S, Liu L, et al. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway:New roles for an old timer [J]. Dev Biol,2006, 299:1-11
[6]John GB, Gallardo TD, Shirley LJ, et al. Foxo3 is a PI3Kdependent molecular switch controlling the initiation of oocyte growth [J].Developmental Biology,2008,321:197-204
[7]Rosselli M Keller P J, Dubey R K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction [J]. Hum Reprod. Update,1998,4:3-24
[8]Tabata, M-aHaS. Nitric oxide and ovarian function [J]. Animal. Science. Journal,2006, 77:275-284
[9]Engels K, Knauer SK, Loibl S, et al. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas [J]. Cancer Res,2008,68:5159-5166
[10]Borniquel S, Garcia-Quintans N, Valle I, et al. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration [J]. Mol Cell Biol,2010,30:4035-4044
[11]Yamamura Y, Lee WL, Inoue K, et al. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells [J] J Biol Chem,2006,281:5267-5276
[12]隋旭霞,罗丽莉,傅玉才.新生鼠卵巢FOXO3a表达水平与卵母细胞凋亡的相关性初步研[J]生殖与避孕,2006,26：515-519
[13]隋旭霞,傅玉才,罗丽莉.Foxo3a转录因子参与卵母细胞的凋亡[J].中国现代医学杂志,2007,17：1438-1441
[14]Matsumi H, Yano T, Koji T, et al. Expression and localization of inducible nitric oxide synthase in the rat ovary:a possible involvement of nitric oxide in the follicular development. Biochem. Biophys [J]. Res. Commun.,1998,243:67-72
[15]van den Hurk R, Zhao J. Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles [J]. Theriogenology,2005,63:1717-1751
[16]Ha KS, Kim K M, Kwon YG, et al.Nitric oxide prevents 6-hydroxydopamine-induced apoptosis in PC12 cells through cGMP-dependent PI3 kinase/Akt activation [J].FASEB J, 2003,17:1036-1047
[17]D. Jeannean Carver, Benjamin Gaston, Kimberly deRonde, Akt-Mediated Activation of HIF-1 in Pulmonary Vascular Endothelial Cells by S-Nitrosoglutathione [J].Am J Respir Cell Mol Biol,2007,37:255-263
[1]Kerr J F R, Wyllie A H, Curie A R. Apoptos is:a basic b iological phenom enonw ith w ide ranging im p licat ion in t issue k inet ics [J]. B r J Cancer,1972,26:239-257
[2]Escobar ML, Echeverria OM, Ortiz R, et al. Combined apoptosis and autophagy, the process that eliminates the oocytes of atretic follicles in immature rats [J]. Apoptosis,2008,13: 1253-1266
[3]Escobar ML, Echeverria OM, Sanchez-Sanchez L, et al. Analysis of different cell death processes of prepubertal rat oocytes in vitro [J]. Apoptosis,2010,15:511-526
[4]Basini G, Grasselli F, Ponderato N, et al. Lipid hydroperoxide and cGMP are not involved in nitric oxide inhibition of steroidogenesis in bovine granulosa cells [J]. Reprod Fertil Dev,2000,12:289-295
[5]Basini G, Baratta M, Ponderato N, et al. Is nitric oxide an autocrine modulator of bovine granulosa cell function? [J]. Reprod Fertil Dev,1998,10:471-478
[6]Pawan K. Dubey VT, Ram Pratap Singh, et al. Influence of nitric oxide on steroid synthesis, growth and apoptosis of Buffalo granulosa cells in vitro [J]. Anim. Sci,2011,24:1204-1210
[7]Sarkar S, Korolchuk VI, Renna M, et al. Complex inhibitory effects of nitric oxide on autophagy [J]. Mol Cell,2011,43:19-32
[8]Rabkin SW, Klassen SS. Nitric oxide differentially regulates the gene expression of caspase genes but not some autophagic genes [J]. Nitric Oxide,2007,16:339-347
[9]Rabkin SW. Nitric oxide-induced cell death in the heart:the role of autophagy [J]. Autophagy 2007,3:347-349
[10]Nicholson DW, Thornberry NA. Caspases:killer proteases [J]. Trends Biochem Sci,1997,22: 299-306
[11]Choi JY, Jo MW, Lee EY, et al. The role of autophagy in follicular development and atresia in rat granulosa cells. Fertil Steril.2010,93(8):2532-2537
[12]Rosselli M, Keller P J, Dubey R K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction [J]. Hum.Reprod. Update,1998,4:3-24
[13]Kim YM, Bombeck CA, Billiar TR. Nitric Oxide as a bifunctional regulator of apoptosis. [J].Circ Res,1999,19; 84:253-256
[14]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy [J]. Acta Pharmacol Sin,2011,32:1089-1099
[15]Boya P, Gonzalez-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis [J]. Mol Cell Biol,2005,25:1025-1040
[16]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. [J] Acta Pharmacol Sin,2011; 32:1089-99.
[17]Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G. Inhibition of macroautophagy triggers apoptosis. [J] Mol Cell Biol,2005;25:1025-40.
[18]Jee B C, Kim S H, Moon S Y. Th e rol e of n it ric oxid e on apopt osis in human luteinized granul osa cell s. Immunocyt ochemi cal evidence. [J] Gynecol Obst et Invest,2003,56(3): 143-147.
[19]Chen Q, Yano T, Mat s umi H, et al. Cross-Talk between Fas/Fas ligand system and nitre oxide in the pathway subserv in granulosa cell apoptosi s:a possible regulatory mechanism for ovarian follicle at res ia. [J] Endocrinology,2005,146 (2):808-815.
[2]Lyons CR, Orloff GJ, Cunningham JM. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. [J] J Biol Chem,1992;267:6370-4.
[3]Janssens SP, Shimouchi A, Quertermous T, Bloch DB, Bloch KD. Cloning and expression of a cDNA encoding human endothelium-derived relaxing factor/nitric oxide synthase. [J] J Biol Chem,1992;267:14519-22.
[4]Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T. Molecular cloning and characterization of human endothelial nitric oxide synthase. [J] FEBS Lett,1992;307:287-93.
[5]Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. [J] J Biol Chem,1993;268:17478-88.
[6]戴爱国.一氧化氮合酶基因家族研究进展.国外医学生理病理科学与临床分册,1996.
[7]陈晋文,孙长凯,黄远桂.一氧化氮合酶的若干研究进展.生物化学与生物物理进展,1996；23：293-297.
[8]Vodovotz Y, Russell D, Xie QW, Bogdan C, Nathan C. Vesicle membrane association of nitric oxide synthase in primary mouse macrophages. [J] J Immunol,1995;154:2914-25.
[9]Nathan C, Xie QW. Regulation of biosynthesis of nitric oxide. [J] J Biol Chem,1994;269: 13725-8.
[10]Masters BS, McMillan K, Sheta EA, Nishimura JS, Roman LJ, Martasek P. Neuronal nitric oxide synthase, a modular enzyme formed by convergent evolution:structure studies of a cysteine thiolate-liganded heme protein that hydroxylates L-arginine to produce NO. as a cellular signal. [J] Faseb J,1996; 10:552-8.
[11]Haque MM, Fadlalla M, Wang ZQ, Ray SS, Panda K, Stuehr DJ. Neutralizing a surface charge on the FMN subdomain increases the activity of neuronal nitric-oxide synthase by enhancing the oxygen reactivity of the enzyme heme-nitric oxide complex. [J] J Biol Chem,2009;284:19237-47.
[12]Gorren AC, Mayer B. Tetrahydrobiopterin in nitric oxide synthesis:a novel biological role for pteridines. [J] Curr Drug Metab,2002;3:133-57.
[13]Giovanelli J, Campos KL, Kaufman S. Tetrahydrobiopterin, a cofactor for rat cerebellar nitric oxide synthase, does not function as a reactant in the oxygenation of arginine. [J] Proc Natl Acad Sci U S A,1991;88:7091-5.
[14]Schmidt PP, Lange R, Gorren AC, Werner ER, Mayer B, Andersson KK. Formation of a protonated trihydrobiopterin radical cation in the first reaction cycle of neuronal and endothelial nitric oxide synthase detected by electron paramagnetic resonance spectroscopy. [J]J Biol Inorg Chem,2001;6:151-8.
[15]Wei CC, Wang ZQ, Wang Q, Meade AL, Hemann C, Hille R, Stuehr DJ. Rapid kinetic studies link tetrahydrobiopterin radical formation to heme-dioxy reduction and arginine hydroxylation in inducible nitric-oxide synthase. [J] J Biol Chem,2001;276:315-9.
[16]Du M, Yeh HC, Berka V, Wang LH, Tsai AL. Redox properties of human endothelial nitric-oxide synthase oxygenase and reductase domains purified from yeast expression system. [J] J Biol Chem,2003;278:6002-11.
[17]Hemmens B, Goessler W, Schmidt K, Mayer B. Role of bound zinc in dimer stabilization but not enzyme activity of neuronal nitric-oxide synthase. [J] J Biol Chem,2000;275:35786-91.
[18]Hurshman AR, Krebs C, Edmondson DE, Marletta MA. Ability of tetrahydrobiopterin analogues to support catalysis by inducible nitric oxide synthase:formation of a pterin radical is required for enzyme activity. [J] Biochemistry,2003;42:13287-303.
[19]Gorren AC, Kungl AJ, Schmidt K, Werner ER, Mayer B. Electrochemistry of pterin cofactors and inhibitors of nitric oxide synthase. [J] Nitric Oxide,2001;5:176-86.
[20]Vogel HJ. The Merck Frosst Award Lecture 1994. Calmodulin:a versatile calcium mediator protein. [J] Biochem Cell Biol,1994;72:357-76.
[21]O'Neil KT, DeGrado WF. How calmodulin binds its targets:sequence independent recognition of amphiphilic alpha-helices. [J] Trends Biochem Sci,1990;15:59-64.
[22]Cho HJ, Xie QW, Calaycay J, Mumford RA, Swiderek KM, Lee TD, Nathan C. Calmodulin is a subunit of nitric oxide synthase from macrophages. [J] J Exp Med,1992; 176:599-604.
[23]Jones RJ, Smith SM, Gao YT, DeMay BS, Mann KJ, Salerno KM, Salerno JC. The function of the small insertion in the hinge subdomain in the control of constitutive mammalian nitric-oxide synthases. [J] J Biol Chem,2004;279:36876-83.
[24]Roman LJ, Masters BS. Electron transfer by neuronal nitric-oxide synthase is regulated by concerted interaction of calmodulin and two intrinsic regulatory elements. [J] J Biol Chem, 2006;281:23111-8.
[25]Heinzel B, John M, Klatt P, Bohme E, Mayer B. Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. [J] Biochem J,1992;281 (Pt 3):627-30.
[26]Schmidt HH, Smith RM, Nakane M, Murad F. Ca2+/calmodulin-dependent NO synthase type I:a biopteroflavoprotein with Ca2+/calmodulin-independent diaphorase and reductase activities. [J] Biochemistry,1992;31:3243-9.
[27]Abu-Soud HM, Yoho LL, Stuehr DJ. Calmodulin controls neuronal nitric-oxide synthase by a dual mechanism. Activation of intra-and interdomain electron transfer. [J] J Biol Chem,1994;269:32047-50.
[28]Wang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ. Three-dimensional structure of NADPH-cytochrome P450 reductase:prototype for FMN-and FAD-containing enzymes. [J] Proc Natl Acad Sci U S A,1997;94:8411-6.
[29]Garcin ED, Bruns CM, Lloyd SJ, Hosfield DJ, Tiso M, Gachhui R, Stuehr DJ, Tainer JA, Getzoff ED. Structural basis for isozyme-specific regulation of electron transfer in nitric-oxide synthase. [J] J Biol Chem,2004;279:37918-27.
[30]Alderton WK, Cooper CE, Knowles RG Nitric oxide synthases:structure, function and inhibition. [J] Biochem J,2001;357:593-615.
[31]Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR, Snyder SH. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. [J] Nature,1991;351: 714-8.
[32]Matsuo R, Misawa K, Ito E. Genomic structure of nitric oxide synthase in the terrestrial slug is highly conserved. [J] Gene,2008;415:74-81.
[33]Klatt P, Schmidt K, Uray G, Mayer B. Multiple catalytic functions of brain nitric oxide synthase. Biochemical characterization, cofactor-requirement, and the role of N omega-hydroxy-L-arginine as an intermediate. [J] J Biol Chem,1993;268:14781-7.
[34]Schulz R, Panas DL, Catena R, Moncada S, Olley PM, Lopaschuk GD. The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. [J] Br J Pharmacol,1995;114:27-34.
[35]张奕华.一氧化氮合酶抑制剂研究进展.药学进展,1997；21：147-151.
[36]Wu CC, Chen SJ, Szabo C, Thiemermann C, Vane JR. Aminoguanidine attenuates the delayed circulatory failure and improves survival in rodent models of endotoxic shock. [J] Br J Pharmacol,1995; 114:1666-72.
[37]Wildhirt SM, Suzuki H, Wolf WP, Dudek R, Horstman D, Weismueller S, Reichart B. S-methylisothiourea inhibits inducible nitric oxide synthase and improves left ventricular performance after acute myocardial infarction. [J] Biochem Biophys Res Commun,1996;227: 328-33.
[38]刘昭前,周宏灏.一氧化氮合酶抑制剂的研究进展.中国药理学通报,1999；15：11-14.
[39]Ignarro LJ, Napoli C, Loscalzo J. Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide:an overview. [J] Circ Res,2002;90:21-8.
[40]Bryan NS, Bian K, Murad F. Discovery of the nitric oxide signaling pathway and targets for drug development. [J] Front Biosci,2009;14:1-18.
[41]Ignarro LJ. Nitric oxide. [J]Curr Top Med Chem,2005;5:595.
[42]Groneberg D, Konig P, Wirth A, Offermanns S, Koesling D, Friebe A. Smooth muscle-specific deletion of nitric oxide-sensitive guanylyl cyclase is sufficient to induce hypertension in mice. [J] Circulation,2010; 121:401-9.
[43]Koesling D, Friebe A. Soluble guanylyl cyclase:structure and regulation. [J] Rev Physiol Biochem Pharmacol,1999;135:41-65.
[44]Shi F, Stewart RL, Jr., Perez E, Chen JY, LaPolt PS. Cell-specific expression and regulation of soluble guanylyl cyclase alpha 1 and beta 1 subunits in the rat ovary. [J] Biol Reprod,2004;70:1552-61.
[45]Revelli A, Ghigo D, Moffa F, Massobrio M, Tur-Kaspa I. Guanylate cyclase activity and sperm function. [J] Endocr Rev,2002;23:484-94.
[46]Buechler WA, Nakane M, Murad F. Expression of soluble guanylate cyclase activity requires both enzyme subunits. [J] Biochem Biophys Res Commun,1991;174:351-7.
[47]Kimura H, Mittal CK, Murad F. Activation of guanylate cyclase from rat liver and other tissues by sodium azide. [J] J Biol Chem,1975;250:8016-22.
[48]Ignarro LJ, Degnan JN, Baricos WH, Kadowitz PJ, Wolin MS. Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient, heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. [J] Biochim Biophys Acta,1982;718:49-59.
[49]Stone JR, Marletta MA. Soluble guanylate cyclase from bovine lung:activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. [J] Biochemistry,1994;33:5636-40.
[50]Wedel B, Humbert P, Harteneck C, Foerster J, Malkewitz J, Bohme E, Schultz G, Koesling D. Mutation of His-105 in the beta 1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. [J] Proc Natl Acad Sci U S A,1994;91:2592-6.
[51]Katsuki S, Arnold W, Mittal C, Murad F. Stimulation of guanylate cyclase by sodium nitroprusside, nitroglycerin and nitric oxide in various tissue preparations and comparison to the effects of sodium azide and hydroxylamine. [J] J Cyclic Nucleotide Res,1977;3:23-35.
[52]Denninger JW, Marletta MA. Guanylate cyclase and the.NO/cGMP signaling pathway. [J] Biochim Biophys Acta,1999;1411:334-50.
[53]Zaccolo M, Movsesian MA. cAMP and cGMP signaling cross-talk:role of phosphodiesterases and implications for cardiac pathophysiology. [J] Circ Res,2007;100: 1569-78.
[54]Francis SH, Turko IV, Corbin JD. Cyclic nucleotide phosphodiesterases:relating structure and function. [J] Prog Nucleic Acid Res Mol Biol,2001;65:1-52.
[55]Soderling SH, Beavo JA. Regulation of cAMP and cGMP signaling:new phosphodiesterases and new functions. [J] Curr Opin Cell Biol,2000; 12:174-9.
[56]Omori K, Kotera J. Overview of PDEs and their regulation. [J] Circ Res,2007; 100:309-27.
[57]Lugnier C. Cyclic nucleotide phosphodiesterase (PDE) superfamily:a new target for the development of specific therapeutic agents. [J] Pharmacol Ther,2006; 109:366-98.
[58]Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated,3',5'-cyclic nucleotide phosphodiesterases. [J] J Biol Chem,1996;271: 796-806.
[59]Yan C, Bentley JK, Sonnenburg WK, Beavo JA. Differential expression of the 61 kDa and 63 kDa calmodulin-dependent phosphodiesterases in the mouse brain. [J] J Neurosci,1994; 14: 973-84.
[60]Yu J, Wolda SL, Frazier AL, Florio VA, Martins TJ, Snyder PB, Harris EA, McCaw KN, Farrell CA, Steiner B, Bentley JK, Beavo JA, Ferguson K, Gelinas R. Identification and characterisation of a human calmodulin-stimulated phosphodiesterase PDE1B1. [J] Cell Signal,1997;9:519-29.
[61]Yan C, Zhao AZ, Bentley JK, Beavo JA. The calmodulin-dependent phosphodiesterase gene PDE1C encodes several functionally different splice variants in a tissue-specific manner. [J] J Biol Chem,1996;271:25699-706.
[62]Martinez SE, Wu AY, Glavas NA, Tang XB, Turley S, Hol WG, Beavo JA. The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. [J] Proc Natl Acad Sci U S A,2002;99:13260-5.
[63]Sadhu K, Hensley K, Florio VA, Wolda SL. Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. [J] J Histochem Cytochem,1999;47:895-906.
[64]Degerman E, Belfrage P, Manganiello VC. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). [J] J Biol Chem,1997;272:6823-6.
[65]Reinhardt RR, Chin E, Zhou J, Taira M, Murata T, Manganiello VC, Bondy CA. Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. [J] J Clin Invest,1995;95:1528-38.
[66]Corbin JD, Turko IV, Beasley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. [J] Eur J Biochem,2000;267:2760-7.
[67]Yanaka N, Kotera J, Ohtsuka A, Akatsuka H, Imai Y, Michibata H, Fujishige K, Kawai E, Takebayashi S, Okumura K, Omori K. Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. [J] Eur J Biochem,1998;255:391-9.
[68]Kotera J, Fujishige K, Imai Y, Kawai E, Michibata H, Akatsuka H, Yanaka N, Omori K. Genomic origin and transcriptional regulation of two variants of cGMP-binding cGMP-specific phosphodiesterases. [J] Eur J Biochem,1999;262:866-73.
[69]Cote RH. Characteristics of photoreceptor PDE (PDE6):similarities and differences to PDE5. [J] Int J Impot Res,2004;16 Suppl 1:S28-33.
[70]Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. [J] J Biol Chem,1998;273: 15559-64.
[71]Guipponi M, Scott HS, Kudoh J, Kawasaki K, Shibuya K, Shintani A, Asakawa S, Chen H, Lalioti MD, Rossier C, Minoshima S, Shimizu N, Antonarakis SE. Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3:alternative splicing of mRNA transcripts, genomic structure and sequence. [J] Hum Genet,1998;103:386-92.
[72]Fujishige K, Kotera J, Michibata H, Yuasa K, Takebayashi S, Okumura K, Omori K. Cloning and characterization of a novel human phosphodiesterase that hydrolyzes both cAMP and cGMP (PDE10A). [J] J Biol Chem,1999;274:18438-45.
[73]Siuciak JA, Chapin DS, Harms JF, Lebel LA, McCarthy SA, Chambers L, Shrikhande A, Wong S, Menniti FS, Schmidt CJ. Inhibition of the striatum-enriched phosphodiesterase PDE10A:a novel approach to the treatment of psychosis. [J] Neuropharmacology,2006;51: 386-96.
[74]Yuasa K, Kotera J, Fujishige K, Michibata H, Sasaki T, Omori K. Isolation and characterization of two novel phosphodiesterase PDE11A variants showing unique structure and tissue-specific expression. [J] J Biol Chem,2000;275:31469-79.
[75]Fawcett L, Baxendale R, Stacey P, McGrouther C, Harrow I, Soderling S, Hetman J, Beavo JA, Phillips SC. Molecular cloning and characterization of a distinct human phosphodiesterase gene family:PDE11A. [J] Proc Natl Acad Sci USA,2000;97:3702-7.
[76]Hetman JM, Robas N, Baxendale R, Fidock M, Phillips SC, Soderling SH, Beavo JA. Cloning and characterization of two splice variants of human phosphodiesterase 11 A. [J] Proc Natl Acad Sci USA,2000;97:12891-5.
[77]Sharron H. Francis MDH, and Marco Conti. Phosphodiesterase Inhibitors:Factors That Influence Potency, Selectivity, and Action. [M]Handbook of Experimental Pharmacology 2011.
[78]Rosselli M, Keller PJ, Dubey RK. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. [J]Hum Reprod Update,1998;4:3-24.
[79]Hess KA, Waltz SE, Toney-Earley K, Degen SJ. The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxide synthase levels and ovulation. [J] Fertil Steril,2003;80 Suppl 2:747-54.
[80]Bredt DS, Hwang PM, Snyder SH. Localization of nitric oxide synthase indicating a neural role for nitric oxide. [J] Nature,1990;347:768-70.
[81]Venema RC, Nishida K, Alexander RW, Harrison DG, Murphy TJ. Organization of the bovine gene encoding the endothelial nitric oxide synthase. [J] Biochim Biophys Acta,1994;1218: 413-20.
[82]Tabata M-aHaS. Nitric oxide and ovarian function. [J] Animal Science Journal,2006;77.
[83]Kim H, Moon C, Ahn M, Lee Y, Kim H, Kim S, Ha T, Jee Y, Shin T. Expression of nitric oxide synthase isoforms in the porcine ovary during follicular development. [J] J Vet Sci,2005;6:97-101.
[84]Jablonka-Shariff A, Olson LM. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology,1997;138:460-8.
[85]Van Voorhis BJ, Moore K, Strijbos PJ, Nelson S, Baylis SA, Grzybicki D, Weiner CP. Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. [J] J Clin Invest,1995;96:2719-26.
[86]Zackrisson U, Mikuni M, Wallin A, Delbro D, Hedin L, Brannstrom M. Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. [J] Hum Reprod,1996;11:2667-73.
[87]Bryant CE, Tomlinson A, Mitchell JA, Thiemermann C, Willoughby DA. Nitric oxide synthase in the rat fallopian tube is regulated during the oestrous cycle. [J] J Endocrino,1995;146:149-57.
[88]Zhang W, Wei QW, Wang ZC, Ding W, Wang W, Shi FX. Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovaries of neonatal and immature rats. [J] J Zhejiang Univ Sci B,2011;12:55-64.
[89]Bonavera JJ, Sahu A, Kalra PS, Kalra SP. Evidence that nitric oxide may mediate the ovarian steroid-induced luteinizing hormone surge:involvement of excitatory amino acids. [J] Endocrinology,1993;133:2481-7.
[90]Rettori V, Belova N, Dees WL, Nyberg CL, Gimeno M, McCann SM. Role of nitric oxide in the control of luteinizing hormone-releasing hormone release in vivo and in vitro. [J] Proc Natl Acad Sci USA,1993;90:10130-4.
[91]Chatterjee S, Collins TJ, Yallampalli C. Inhibition of nitric oxide facilitates LH release from rat pituitaries. [J] Life Sci,1997;61:45-50.
[92]Matsumi H, Koji T, Yano T, Yano N, Tsutsumi O, Momoeda M, Osuga Y, Taketani Y. Evidence for an inverse relationship between apoptosis and inducible nitric oxide synthase expression in rat granulosa cells:a possible role of nitric oxide in ovarian follicle atresia [J] Endocr J,1998;45:745-51.
[93]Faletti A, Perez Martinez S, Perotti C, de Gimeno MA. Activity of ovarian nitric oxide synthase (NOs) during ovulatory process in the rat:relationship with prostaglandins (PGs) production. [J] Nitric Oxide,1999;3:340-7.
[1]Fortune JE, Armstrong DT. Androgen production by theca and granulosa isolated from proestrous rat follicles. [J] Endocrinology,1977;100:1341-7.
[2]McNatty KP, Makris A, DeGrazia C, Osathanondh R, Ryan KJ. The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro. [J] J Clin Endocrinol Metab,1979;49:687-99.
[3]Cohen P, Antoniw JF, Nimmo HG, Yeaman SJ. Protein phosphorylation and hormone action. [J] Ciba Found Symp,1976;41:281-95.
[4]王宁玲.大鼠卵巢原始卵泡形成和发育相关蛋白谱系的构建及功能研究.[D]南京医科大学,2007：p5.
[5]Edwards RG, Fowler RE, Gore-Langton RE, Gosden RG, Jones EC, Readhead C, Steptoe PC. Normal and abnormal follicular growth in mouse, rat and human ovaries. [J] J Reprod Fertil,1977;51:237-63.
[6]McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. [J] Endocr Rev,2000;21:200-14.
[7]Baker TG, Franchi LL. The fine structure of oogonia and oocytes in human ovaries. [J] J Cell Sci,1967;2:213-24.
[8]Sathananthan AH, Selvaraj K, Trounson A. Fine structure of human oogonia in the foetal ovary. [J] Mol Cell Endocrino,12000;161:3-8.
[9]Gondos B. Comparative studies of normal and neoplastic ovarian germ cells:1. Ultrastructure of oogonia and intercellular bridges in the fetal ovary. [J] Int J Gynecol Pathol,1987;6:114-23.
[10]Gondos B. Comparative studies of normal and neoplastic ovarian germ cells:2. Ultrastructure and pathogenesis of dysgerminoma. [J] Int J Gynecol Pathol,1987;6:124-31.
[11]van Wezel IL, Rodgers RJ. Morphological characterization of bovine primordial follicles and their environment in vivo. Biol Reprod 11996;55:1003-11.
[12]Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. [J] Dev Biol,2001;234:339-51.
[13]高辉,郁琦,徐苓.原始卵泡的形成与发育生殖医学杂志.[J]生殖医学杂志,2007；16：253-55.
[14]Pepling ME, Spradling AC. Female mouse germ cells form synchronously dividing cysts. [J] Development,1998; 125:3323-8.
[15]Kezele P, Nilsson EE, Skinner MK. Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. [J] Biol Reprod,2005;73: 967-73.
[16]Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. [J] Mol Hum Reprod,2006;12:61-9.
[17]Holt JE, Jackson A, Roman SD, Aitken RJ, Koopman P, McLaughlin EA. CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary. [J] Dev Biol,2006; 293:449-60.
[18]Nilsson E, Rogers N, Skinner MK. Actions of anti-Mullerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition. [J] Reproduction,2007;134: 209-21.
[19]Dono R, Texido G, Dussel R, Ehmke H, Zeller R. Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. [J] Embo J,1998;17:4213-25.
[20]Dissen GA, Romero C, Paredes A, Ojeda SR. Neurotrophic control of ovarian development. [J] Microsc Res Tech,2002;59:509-15.
[21]Paredes A, Romero C, Dissen GA, DeChiara TM, Reichardt L, Cornea A, Ojeda SR, Xu B. TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. [J] Dev Biol,2004;267:430-49.
[22]Spears N, Molinek MD, Robinson LL, Fulton N, Cameron H, Shimoda K, Telfer EE, Anderson RA, Price DJ. The role of neurotrophin receptors in female germ-cell survival in mouse and human. [J] Development,2003;130:5481-91.
[23]Mazerbourg S, Klein C, Roh J, Kaivo-Oja N, Mottershead DG, Korchynskyi O, Ritvos O, Hsueh AJ. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. [J] Mol Endocrinol,2004;18:653-65.
[24]Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. [J] Nature,1996;383:531-5.
[25]Hayashi M, McGee EA, Min G, Klein C, Rose UM, van Duin M, Hsueh AJ. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. [J] Endocrinology,1999; 140:1236-44.
[26]Aaltonen J, Laitinen MP, Vuojolainen K, Jaatinen R, Horelli-Kuitunen N, Seppa L, Louhio H, Tuuri T, Sjoberg J, Butzow R, Hovata O, Dale L, Ritvos O. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. [J] J Clin Endocrinol Metab,1999;84:2744-50.
[27]Bodensteiner KJ, McNatty KP, Clay CM, Moeller CL, Sawyer HR. Expression of growth and differentiation factor-9 in the ovaries of fetal sheep homozygous or heterozygous for the inverdale prolificacy gene (FecX(Ⅰ)). [J] Biol Reprod,2000;62:1479-85.
[28]Wassarman PM, Albertini, D.F. The mammalian ovum. In:Knobil, E., Neill, J.D. (Eds.), [M] The Physiology of Reproduction.994.
[29]Eppig JJ, Viveiros, M.M., Bivens, C.M., De La Fuente, R. Regulation of mammalian oocyte maturation. In:Leung, P.C., Adashi, E.Y. (Eds.), [M] The Ovary,2004.
[30]Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. [J] Reproduction,2001;122:829-38.
[31]Elvin JA, Matzuk MM. Mouse models of ovarian failure. [J] Rev Reprod,1998;3:183-95.
[32]Soyal SM, Amleh A, Dean J. FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. [J] Development,2000;127:4645-54.
[33]Castrillon DH, Miao L, Kollipara R, Homer JW, DePinho RA. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. [J] Science,2003;301:215-8.
[34]Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. [J] Science,2004;305:1157-9.
[35]Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, Treier M. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. [J] Developmen,2004;131:933-42.
[36]Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, Matzuk MM, Rajkovic A. Oogenesis requires germ cell-specific transcriptional regulators Sohlhl and Lhx8. [J] Proc Natl Acad Sci U SA,2006;103:8090-5.
[37]Albertini DF, Barrett SL. Oocyte-somatic cell communication. [J] Reprod Suppl,2003;61: 49-54.
[38]Shimasaki S, Moore RK, Otsuka F, Erickson GF. The bone morphogenetic protein system in mammalian reproduction. [J] Endocr Rev,2004;25:72-101.
[39]Vanderhyden B. Molecular basis of ovarian development and function. [J] Front Biosci,2002;7:d2006-22.
[40]Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. [J] Proc Natl Acad Sci U S A,2002;99:2890-4.
[41]Hashimoto O, Moore RK, Shimasaki S. Posttranslational processing of mouse and human BMP-15:potential implication in the determination of ovulation quota. [J] Proc Natl Acad Sci U S A,2005; 102:5426-31.
[42]Thomas FH, Ethier JF, Shimasaki S, Vanderhyden BC. Follicle-stimulating hormone regulates oocyte growth by modulation of expression of oocyte and granulosa cell factors. [J] Endocrinology,2005;146:941-9.
[43]Albertini DF, Combelles CM, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. [J] Reproduction,2001;121:647-53.
[44]Kidder GM, Mhawi AA. Gap junctions and ovarian folliculogenesis. [J] Reproduction,2002;123:613-20.
[45]Vanhaesebroeck B, Alessi DR. The PI3K-PDK1 connection:more than just a road to PKB. [J] Biochem J,2000;346 Pt 3:561-76.
[46]Weigel D, Jurgens G, Kuttner F, Seifert E, Jackle H. The homeotic gene fork head encodes a nuclear protein and is expressed in the terminal regions of the Drosophila embryo. [J] Cell,1989;57:645-58.
[47]Ronnebaum SM, Patterson C. The FoxO family in cardiac function and dysfunction. [J] Annu Rev Physiol,2010,72:81-94.
[48]Zhang X, Rielland M, Yalcin S, Ghaffari S. Regulation and function of FoxO transcription factors in normal and cancer stem cells:what have we learned? [J] Curr Drug Targets,2011; 12:1267-83.
[49]Shi F, LaPolt PS. Relationship between FoxO1 protein levels and follicular development, atresia, and luteinization in the rat ovary. [J] J Endocrinol,2003; 179:195-203.
[50]李学斌,谢庄,石放雄.FOXO蛋白的修饰和细胞凋亡和癌变.[J]生物化学和生物物理进展,2005；32：600-06.
[51]Khan J, Bittner ML, Saal LH, Teichmann U, Azorsa DO, Gooden GC, Pavan WJ, Trent JM, Meltzer PS. cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene. [J] Proc Natl Acad Sci U S A,1999;96:13264-9.
[52]Yamamura Y, Lee WL, Inoue K, Ida H, Ito Y. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. [J] J Biol Chem,2006;281:5267-76.
[53]隋旭霞,罗丽莉,傅玉才.新生鼠卵巢FOXO3a表达水平与卵母细胞凋亡的相关性初步研.[J]生殖与避孕,2006；26：515-19.
[54]隋旭霞,傅玉才,罗丽莉.Foxo3a转录因子参与卵母细胞的凋亡.[J]中国现代医学杂志,2007；17：1438-41.
[55]Leslie NR, Downes CP. PTEN:The down side of PI 3-kinase signalling. [J] Cell Signal,2002;14:285-95.
[56]Sulis ML, Parsons R. PTEN:from pathology to biology. [J] Trends Cell Biol,2003;13: 478-83.
[57]Parsons R. Human cancer, PTEN and the PI-3 kinase pathway. [J] Semin Cell Dev Biol,2004;15:171-6.
[58]Reddy P, Liu L, Adhikari D, Jagarlamudi K, Rajareddy S, Shen Y, Du C, Tang W, Hamalainen T, Peng SL, Lan ZJ, Cooney AJ, Huhtaniemi I, Liu K. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. [J] Science,2008;319: 611-3.
[59]John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. [J] Dev Biol,2008;321:197-204.
[60]Liu K, Rajareddy S, Liu L, Jagarlamudi K, Boman K, Selstam G, Reddy P. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway:new roles for an old timer. [J] Dev Biol,2006;299:1-11.
[61]TABATA M-aHaS. Nitric oxide and ovarian function. [J] Animal Science Journal,2006;77.
[62]Van Voorhis BJ, Dunn MS, Snyder GD, Weiner CP. Nitric oxide:an autocrine regulator of human granulosa-luteal cell steroidogenesis. [J] Endocrinology,1994;135:1799-806.
[63]Jablonka-Shariff A, Olson LM. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology,1997;138:460-8.
[64]Van Voorhis BJ, Moore K, Strijbos PJ, Nelson S, Baylis SA, Grzybicki D, Weiner CP. Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. [J] J Clin Invest,1995;96:2719-26.
[65]Zackrisson U, Mikuni M, Wallin A, Delbro D, Hedin L, Brannstrom M. Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. [J] Hum Reprod,1996;11:2667-73.
[66]Takesue K, Hattori MA, Nishida N, Kato Y, Fujihara N. Expression of endothelial nitric oxide synthase gene in cultured porcine granulosa cells after FSH stimulation. [J] J Mol Endocrinol,2001;26:259-65.
[67]Shi F, Stewart RL, Jr., Perez E, Chen JY, LaPolt PS. Cell-specific expression and regulation of soluble guanylyl cyclase alpha 1 and beta 1 subunits in the rat ovary. Biol Reprod,2004;70: 1552-61.
[68]Gregg AR. Mouse models and the role of nitric oxide in reproduction. [J] Curr Pharm Des,2003;9:391-8.
[69]Jablonka-Shariff A, Ravi S, Beltsos AN, Murphy LL, Olson LM. Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice. [J] Biol Reprod,1999;61:171-7.
[70]Pallares P, Garcia-Fernandez RA, Criado LM, Letelier CA, Esteban D, Fernandez-Toro JM, Flores JM, Gonzalez-Bulnes A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008;136:573-9.
[71]Gregg AR, Schauer A, Shi O, Liu Z, Lee CG, O'Brien WE. Limb reduction defects in endothelial nitric oxide synthase-deficient mice. [J] Am J Physiol,1998;275:H2319-24.
[72]Jablonka-Shariff A, Olson LM. The role of nitric oxide in oocyte meiotic maturation and ovulation:meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. [J] Endocrinology,1998; 139:2944-54.
[73]Hefler LA, Gregg AR. Inducible and endothelial nitric oxide synthase:genetic background affects ovulation in mice. [J] Fertil Steril,2002;77:147-51.
[74]Gyurko R, Leupen S, Huang PL. Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in hypogonadism and infertility. [J] Endocrinology,2002;143:2767-74.
[75]Tsutsui M, Shimokawa H, Morishita T, Nakashima Y, Yanagihara N. Development of genetically engineered mice lacking all three nitric oxide synthases. [J] J Pharmacol Sci,2006;102:147-54.
[76]Zhang W, Wei QW, Wang ZC, Ding W, Wang W, Shi FX. Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovaries of neonatal and immature rats. [J] J Zhejiang Univ Sci B,2011;12:55-64.
[77]LaPolt PS, Leung K, Ishimaru R, Tafoya MA, You-hsin Chen J. Roles of cyclic GMP in modulating ovarian functions. [J] Reprod Biomed Online,2003;6:15-23.
[78]Ishimaru RS, Leung K, Hong L, LaPolt PS. Inhibitory effects of nitric oxide on estrogen production and cAMP levels in rat granulosa cell cultures. [J] J Endocrinol,2001;168:249-55.
[79]Grasselli F, Ponderato N, Basini G, Tamanini C. Nitric oxide synthase expression and nitric oxide/cyclic GMP pathway in swine granulosa cells. [J] Domest Anim Endocrinol,2001;20: 241-52.
[80]Engels K, Knauer SK, Loibl S, Fetz V, Harter P, Schweitzer A, Fisseler-Eckhoff A, Kommoss F, Hanker L, Nekljudova V, Hermanns I, Kleinert H, Mann W, du Bois A, Stauber RH. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. [J] Cancer Res,2008;68:5159-66.
[81]Borniquel S, Garcia-Quintans N, Valle I, Olmos Y, Wild B, Martinez-Granero F, Soria E, Lamas S, Monsalve M. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration. [J] Mol Cell Biol,2010;30: 4035-44.
[1]Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics.[J] Br J Cancer,1972;26:239-57.
[2]Herr I, Debatin KM. Cellular stress response and apoptosis in cancer therapy. [J] Blood,2001;98:2603-14.
[3]刘光伟龚守良.细胞凋亡信号传导途径的研究进展.[J]吉林大学学报(医学版),2004；30：485-88.
[4]Hotchkiss RS. Cell Death. [J] N Engl J Med,2009;361:1570-83.
[5]戴昕,李占全,冀林华.凋亡相关蛋白Caspase研究进展.[J]中国现代医药杂志,2010；12：130-32.
[6]Villa P KS, Earnshaw WC. Caspases and caspase inhibitors. [J] TIBS,1997;22.
[7]Fernandes-Alnemri T, Litwack G, Alnemri ES. CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. [J] J Biol Chem,1994;269:30761-4.
[8]Nicholson DW, Thornberry NA. Caspases:killer proteases. [J] Trends Biochem Sci,1997;22: 299-306.
[9]Hishikawa K, Nakaki T, Fujii T. Connective tissue growth factor induces apoptosis via caspase 3 in cultured human aortic smooth muscle cells. [J] Eur J Pharmacol,2000;392: 19-22.
[10]Buckley CD, Pilling D, Henriquez NV, Parsonage G, Threlfall K, Scheel-Toellner D, Simmons DL, Akbar AN, Lord JM, Salmon M. RGD peptides induce apoptosis by direct caspase-3 activation. [J] Nature,1999;397:534-9.
[11]Pru JK TJ. Programmed cell death in the ovary:insights and future prospects using genetic technologies. [J] Mol Endocrinol,2001; 15:845-53.
[12]He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. [J] Annu Rev Genet,2009;43:67-93.
[13]Glick D, Barth S, Macleod KF. Autophagy:cellular and molecular mechanisms. [J] J Pathol,2010; 221:3-12.
[14]Mehrpour M, Esclatine A, Beau I, Codogno P. Overview of macroautophagy regulation in mammalian cells. [J] Cell Res,2010; 20:748-62.
[15]Puyal J, Ginet V, Grishchuk Y, Truttmann AC, Clarke PG Neuronal Autophagy as a Mediator of Life and Death:Contrasting Roles in Chronic Neurodegenerative and Acute Neural Disorders. [J] Neuroscientist,2011.
[16]Yang Z, Klionsky DJ. Mammalian autophagy:core molecular machinery and signaling regulation. [J] Curr Opin Cell Biol,2010;22:124-31.
[17]Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. [J] Mol Biol Cell,2009;20:1981-91.
[18]Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. [J]Mol Biol Cell,2009;20:1992-2003.
[19]Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. [J] Mol Biol Cell,2008;19: 5360-72.
[20]Liang C, Sir D, Lee S, Ou JH, Jung JU. Beyond autophagy:the role of UVRAG in membrane trafficking. [J] Autophagy,2008;4:817-20.
[21]Sun Q, Fan W, Chen K, Ding X, Chen S, Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. [J] Proc Natl Acad Sci U S A,2008;105:19211-6.
[22]Longatti A, Tooze SA. Vesicular trafficking and autophagosome formation. [J]Cell Death Differ,2009; 16:956-65.
[23]Mizushima N, Kuma A, Kobayashi Y, Yamamoto A, Matsubae M, Takao T, Natsume T, Ohsumi Y, Yoshimori T. Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. [J] J Cell Sci,2003;116: 1679-88.
[24]Nakatogawa H, Ichimura Y, Ohsumi Y. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion. [J] Cell,2007; 130: 165-78.
[25]Wu Y, Li X, Zhu JX, Xie W, Le W, Fan Z, Jankovic J, Pan T. Resveratrol-Activated AMPK/SIRT1/Autophagy in Cellular Models of Parkinson's Disease. [J] Neurosignals,2011; 19:163-74.
[26]Yang DS, Kumar A, Stavrides P, Peterson J, Peterhoff CM, Pawlik M, Levy E, Cataldo AM, Nixon RA. Neuronal apoptosis and autophagy cross talk in aging PS/APP mice, a model of Alzheimer's disease. [J] Am J Pathol,2008;173:665-81.
[27]Gonzalez-Polo RA, Boya P, Pauleau AL, Jalil A, Larochette N, Souquere S, Eskelinen EL, Pierron G, Saftig P, Kroemer G. The apoptosis/autophagy paradox:autophagic vacuolization before apoptotic death. [J] J Cell Sci,2005;118:3091-102.
[28]Boya P, Kroemer G. Lysosomal membrane permeabilization in cell death. [J] Oncogene,2008;27:6434-51.
[29]Peri P, Nuutila K, Vuorinen T, Saukko P, Hukkanen V. Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells. [J] J Gen Virol,2010; 92:173-80.
[30]Almaguel FG, Liu JW, Pacheco FJ, De Leon D, Casiano CA, De Leon M. Lipotoxicity-mediated cell dysfunction and death involve lysosomal membrane permeabilization and cathepsin L activity. [J] Brain Res,2010; 1318:133-43.
[31]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury:a role of autophagy. [J] Acta Pharmacol Sin,2011; 32:1089-99.
[32]Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G. Inhibition of macroautophagy triggers apoptosis. [J] Mol Cell Biol,2005;25:1025-40.
[33]Galluzzi L, Vicencio JM, Kepp O, Tasdemir E, Maiuri MC, Kroemer G. To die or not to die: that is the autophagic question. [J] Curr Mol Med,2008;8:78-91.
[34]Saiki S, Sasazawa Y, Imamichi Y, Kawajiri S, Fujimaki T, Tanida I, Kobayashi H, Sato F, Sato S, Ishikawa K, Imoto M, Hattori N. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. [J] Autophagy,2011;7:176-87.
[35]Gawriluk TR, Hale AN, Flaws JA, Dillon CP, Green DR, Rucker EB,3rd. Autophagy is a cell survival program for female germ cells in the murine ovary. [J] Reproduction,2011;141: 759-65.
[36]Clarke PG Developmental cell death:morphological diversity and multiple mechanisms. [J] Anat Embryol (Berl),1990;181:195-213.
[37]Baehrecke EH. How death shapes life during development. [J] Nat Rev Mol Cell Biol,2002;3: 779-87.
[38]Ortiz R, Echeverria OM, Salgado R, Escobar ML, Vazquez-Nin GH. Fine structural and cytochemical analysis of the processes of cell death of oocytes in atretic follicles in new born and prepubertal rats. [J] Apoptosis,2006;11:25-37.
[39]Escobar ML, Echeverria OM, Ortiz R, Vazquez-Nin GH. Combined apoptosis and autophagy, the process that eliminates the oocytes of atretic follicles in immature rats. [J] Apoptosis,2008;13:1253-66.
[40]Escobar ML, Echeverria OM, Sanchez-Sanchez L, Mendez C, Pedernera E, Vazquez-Nin GH. Analysis of different cell death processes of prepubertal rat oocytes in vitro. [J] Apoptosis, 2010; 15:511-26.
[41]Pritchett TL, Tanner EA, McCall K. Cracking open cell death in the Drosophila ovary. [J] Apoptosis,2009;14:969-79.
[42]Tingen C, Kim A, Woodruff TK. The primordial pool of follicles and nest breakdown in mammalian ovaries. [J] Mol Hum Reprod,2009;15:795-803.
[43]Tingen CM, Bristol-Gould SK, Kiesewetter SE, Wellington JT, Shea L, Woodruff TK. Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. [J] Biol Reprod,2009;81:16-25.
[44]Lobascio AM, Klinger FG, Scaldaferri ML, Farini D, De Felici M. Analysis of programmed cell death in mouse fetal oocytes. [J] Reproduction,2007;134:241-52.
[45]Choi J, Jo M, Lee E, Choi D. Induction of apoptotic cell death via accumulation of autophagosomes in rat granulosa cells. [J] Fertil Steril,2011; 95:1482-6.
[46]Choi JY, Jo MW, Lee EY, Yoon BK, Choi DS. The role of autophagy in follicular development and atresia in rat granulosa cells. [J] Fertil Steril,2011;93:2532-7.
[47]Basini G, Grasselli F, Ponderato N, Bussolati S, Tamanini C. Lipid hydroperoxide and cGMP are not involved in nitric oxide inhibition of steroidogenesis in bovine granulosa cells. [J] Reprod Fertil Dev 12000; 12:289-95.
[48]Basini G, Baratta M, Ponderato N, Bussolati S, Tamanini C. Is nitric oxide an autocrine modulator of bovine granulosa cell function? [J] Reprod Fertil Dev,1998; 10:471-8.
[49]Pawan K. Dubey VT, Ram Pratap Singh, K.V.H. Sastry, G. Taru Sharma Influence of nitric oxide on steroid synthesis, growth and apoptosis of Buffalo granulosa cells in vitro. [J] J. Anim. Sci,2011;24:1204-10.
[50]Matsumi H, Yano T, Osuga Y, Kugu K, Tang X, Xu JP, Yano N, Kurashima Y, Ogura T, Tsutsumi O, Koji T, Esumi H, Taketani Y. Regulation of nitric oxide synthase to promote cytostasis in ovarian follicular development. [J] Biol Reprod,2000;63:141-6.
[51]Yoon SJ, Choi KH, Lee KA. Nitric oxide-mediated inhibition of follicular apoptosis is associated with HSP70 induction and Bax suppression. [J] Mol Reprod Dev,2002;61:504-10.
[52]Chun SY, Eisenhauer KM, Kubo M, Hsueh AJ. Interleukin-1 beta suppresses apoptosis in rat ovarian follicles by increasing nitric oxide production. Endocrinology,1995; 136:3120-7.
[53]Chu HP, Etgen AM. Ovarian hormone dependence of alpha(1)-adrenoceptor activation of the nitric oxide-cGMP pathway:relevance for hormonal facilitation of lordosis behavior. [J] J Neurosci,1999;19:7191-7.
[54]Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J, Wada O, Koga K, Fujiwara T, Kugu K, Taketani Y. Cross-Talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis:a possible regulatory mechanism for ovarian follicle atresia. [J] Endocrinology,2005; 146:808-15.
[55]Preutthipan S, Chen SH, Tilly JL, Kugu K, Lareu RR, Dharmarajan AM. Inhibition of nitric oxide synthesis potentiates apoptosis in the rabbit corpus luteum. [J] Reprod Biomed Online,2004;9:264-70.
[56]Sarkar S, Korolchuk VI, Renna M, Imarisio S, Fleming A, Williams A, Garcia-Arencibia M, Rose C, Luo S, Underwood BR, Kroemer G, O'Kane CJ, Rubinsztein DC. Complex inhibitory effects of nitric oxide on autophagy. [J] Mol Cell,2011;43:19-32.
[57]Rabkin SW, Klassen SS. Nitric oxide differentially regulates the gene expression of caspase genes but not some autophagic genes. [J] Nitric Oxide,2007;16:339-47.
[58]Rabkin SW. Nitric oxide-induced cell death in the heart:the role of autophagy. [J],2007;3: 347-9.
[1]Rosselli, M., Keller, P.J., Dubey, R.K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. [J] Hum. Reprod. Update,2008; 4:3-24.
[2]Griffith, O.W., Stuehr, D.J. Nitric oxide synthase properties and catalytic mechanism. [J] Annu. Rev. Physiol.,1995; 57:707-736.
[3]Snyder, S.H. Nitric oxide:NO endothelial NO. [J] Nature,1995; 377:196-197.
[4]Nathan, C., Xie, Q.W. Regulation of biosynthesis of nitric oxide. [J] J. Biol. Chem.,1994; 269:13725-13728.
[5]Hattori, M.A., Tabata, S. Nitric oxide and ovarian function. [J] Anim. Sci. J.,2006; 77:275-284.
[6]Kim, H., Moon, C., Ahn, M., Lee, Y., Kim, S., Ha, T., Jee, Y.,Shin, T. Expression of nitric oxide synthase isoforms in the porcine ovary during follicular development. [J] J. Vet. Sci., 2005; 6:97-101.
[7]Olson, L.M., Jones-Burton, C.M., Jablonka-Shariff, A. Nitric oxide decreases estradiol synthesis of rat luteinized ovarian cells:possible role for nitric oxide in functional luteal regression. [J] Endocrinology,1996; 137:3531-3539.
[8]Srivastava, V., Jones, B.J., Dookwah, H., Hiney, J.K., Dees, W.L. Ovarian nitric oxide synthase (NOS) gene expression during peripubertal development. [J] Life Sci.,1997; 61:1507-1516.
[9]Mitchell, L.M., Kennedy, C.R., Hartshorne, G.M. Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles. [J] Hum. Reprod.,2004;19:30-40.
[10]Arnold, W.P., Aldred, R., Murad, F. Cigarette smoke activates guanylate cyclase and increases guanosine3',5'-monophosphate in tissues. [J] Science,1977; 198:934-936.
[11]Nakamura, Y., Yamagata, Y., Sugino, N., Takayama, H., Kato,H. Nitric oxide inhibits oocyte meiotic maturation.Biol. [J] Reprod.,2002; 67:1588-1592.
[12]Chen, Y.H., Tafoya, M., Ngo, A., LaPolt, P.S. Effects of nitric oxide and cGMP on inhibin A and inhibin subunit mRNA levels from cultured rat granulosa cells. [J] Fertil.Steril.,2003; 79:687-693.
[13]Palmer, R.M., Moncada, S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem. Biophys. Res. [J] Commun.,1989; 158:348-352.
[14]Moncada, S., Palmer, R.M., Higgs, E.A. Nitric oxide:physiology, pathophysiology, and pharmacology. [J] Pharmacol. Rev.,1991; 43:109-142.
[15]Lewis, R.S., Deen, W.M. Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. [J] Chem. Res.Toxicol.,1994; 7:568-574
[16]Theilig, F., Bostanjoglo, M., Pavenstadt, H., Grupp, C.,Holland, G., Slosarek, I., Gressner, A.M., Russwurm, M., Koesling, D., Bachmann, S. Cellular distribution and function of soluble guanylyl cyclase in rat kidney and liver. [J] J. Am. Soc. Nephrol.,2001; 12:2209-2220.
[17]Sette, C., Conti, M. Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. [J] J. Biol. Chem.,1996; 271:16526-16534.
[18]Nichols, M.R., Morimoto, B.H. Differential inhibition of multiple cAMP phosphodiesterase isozymes by isoflavones and tyrphostins. [J] Mol. Pharmacol.,2000; 57:738-745.
[19]Tamanini, C.G.B., Grasselli, F., Tirelli, M. Nitric oxide and the ovary. [J] J. Anim. Sci.,2003; 81:E1-E7.
[20]Matsumi, H., Yano, T., Koji, T., Ogura, T., Tsutsumi, O.,Taketani, Y., Esumi, H. Expression and localization of inducible nitric oxide synthase in the rat ovary:a possible involvement of nitric oxide in the follicular development. Biochem. Biophys. [J] Res. Commun.,1998; 243:67-72.
[21]van den Hurk, R., Zhao, J. Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. [J] Theriogenology,2005; 63:1717-1751.
[22]Drazen, D.L., Klein, S.L., Burnett, A.L., Wallach, E.E., Crone,J.K., Huang, P.L., Nelson, R.J. Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase. [J] Nitric. Oxide,1999; 3:366-374.
[23]Jablonka-Shariff, A., Olson, L.M. Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. [J] Endocrinology, 1997; 138:460-468.
[24]Pallares, P., Garcia-Fernandez, R.A., Criado, L.M., Letelier, C.A., Esteban, D., Fernandez-Toro, J.M., Flores, J.M., Gonzalez-Bulnes, A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008; 136:573-579.
[25]Wang, Z., Shi, F., Jiang, Y.Q., Lu, L.Z., Wang, H., Watanabe,G., Taya, K. Changes of cyclic AMP levels and phosphodiesterase activities in the rat ovary. [J] J. Reprod.Dev.,2007; 53:717-725.
[26]Lamprecht, S.A., Zor, U., Tsafriri, A., Lindner, H.R. Action of prostaglandin E 2 and of luteinizing hormone on ovarian adenylate cyclase, protein kinase and ornithine decarboxylase activity during postnatal development and maturity in the rat. [J] J. Endocrinol,1987; 57:217-233.
[27]Sokka, T., Huhtaniemi, I. Ontogeny of gonadotrophin receptors and gonadotrophin-stimulated cyclic AMP production in the neonatal rat ovary. [J] J. Endocrinol.,1990;127:297-303.
[28]Jablonka-Shariff, A., Ravi, S., Beltsos, A.N., Murphy, L.L.,Olson, L.M. Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice. [J] Biol. Reprod.,1999; 61:171-177.
[29]Huang, J., Roby, K.F., Pace, J.L., Russell, S.W., Hunt, J.S. Cellular localization and hormonal regulation of inducible nitric oxide synthase in cycling mouse uterus. [J] J.Leukoc. Biol.,1995; 57:27-35.
[30]McGee, E., Spears, N., Minami, S., Hsu, S.Y., Chun, S.Y.,Billig, H., Hsueh, A.J. Preantral ovarian follicles in serum-free culture:suppression of apoptosis after activation of the cyclic guanosine 3',5'-monophosphate pathway and stimulation of growth and differentiation by follicle-stimulating hormone. [J] Endocrinology,1997; 138:2417-2424.
[31]Shi, F., Stewart, R.L.Jr., Perez, E., Chen, J.Y., LaPolt, P.S. Cell-specific expression and regulation of soluble guanylyl cyclase α1 and β1 subunits in the rat ovary. [J] Biol.Reprod., 2004; 70:1552-1561.
[32]Lancaster, J.R.Jr. A tutorial on the diffusibility and reactivity of free nitric oxide. [J] Nitric. Oxide,1997; 1:18-30.
[33]Kelm, M. Nitric oxide metabolism and breakdown.Biochim. [J] Biophys. Acta,1999; 1411:273-289.
[1]LaPolt PS, Leung K, Ishimaru R, et al. Roles of cyclic GMP in modulating ovarian functions. [J] Reprod Biomed Online,2003; 6:15-23
[2]Mehats C, Andersen CB, Filopanti M, et al. Cyclic nucleotide phosphodiesterases and their role in endocrine cell signalling.[J] Trends Endocrinol Metab.,2002;13:29-35.
[4]Uckert S, Hedlund P, Andersson KE, et al.Update on Phosphodiesterase (PDE) Isoenzymes as Pharmacologic Targets in Urology:Present and Future.[J] Eur Urol.,2006; 50:1194-1207
[3]Francis SH, Turko IV, Corbin JD. Cyclic nucleotide phosphodiesterases:relating structure and function. Prog. [J] Nucleic Acid Res. Mol. Biol.2001; 65:1-52
[5]Masciarelli S, Horner K, Liu C,et al. Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. [J] J Clin Invest.2004; 114:196-205
[6]Effect of Type 3 and Type 4 Phosphodiesterase Inhibitors on the Maintenance of Bovine Oocytes in Meiotic Arrest. [J] Biol Reprod.2002; 66,180-184.
[7]Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. [J] The EMBO Journal,2006; 25:5716-5725
[8]Wei Zhang, Quanwei Wei, Zhengchao Wang, Wei Ding, Wei Wang, Fangxiong Shi, Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovary of neonatal and immature rats. [J] J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2011; 12:55-64
[9]Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. [J] Journal of Hepatology,2006; 44:886-893
[10]Expression and activity of cGMP-dependent phosphodiesterases is up-regulated by lipopolysaccharide (LPS) in rat peritoneal macrophages. [J] Biochimica et Biophysica Acta, 2007;1773:209-218
[11]Overview of PDEs and Their Regulation. [J]Circ Res.2007; 100:309-327
[12]LUGN IER C. Cyclic nucleotide phosphodiesterase (PDE) superfarmily:A new targe t for the development of specif ic the rapeutic agents [J]. Pharmacol Ther,2006; 109:366-398.
[13]Degerman E, Belfrage P, Manganiello VC. Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). [J] J Biol Chem.1997; 272:6823-6826.
[14]Cloning and characterization of the cyclic guanosine monophosphate-inhibited phosphodiesterase PDE3A Expressed in mouse oocyte. [J] Biol Reprod.,2001; 65:188-196
[15]Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes. [J] Biol Reprod.,2009; 81:595-604
[16]Wang Z, Shi F, Jiang Y, Lu L, Watanabe G, Taya K. Changes of cyclic AMP levels and phosphodiesterase activities in the rat ovary. [J] J Reprod Dev.,2007; 53,717-725.
[17]Corbin JD, Turko IV, Beasley A, Francis SH. Phosphorylation of phosphodiesterase-5 by cyclic nucleotide-dependent protein kinase alters its catalytic and allosteric cGMP-binding activities. [J] Eur J Biochem.2000; 267:2760-2767.
[18]Sasseville, M., Guillemette, C., Coulombe, Z., Richard, F.,2005. Detection and potential role of 3'-5'cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase 5A (PDE5A) in porcine ovary. [J] Fertil. Steril.2005; 84 (s1):397
[19]Donato MA, Saraiva KL, Soares e Silva AK, Wanderley MI, Peixoto CA. Follicle development and luteal cell morphology altered by phosphodiesterase-5 inhibitor. [J] Micron. 2009; 40:845-50.
[20]Fisher DA, Smith JF, Pillar JS, St Denis SH, Cheng JB. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. [J] J Biol Chem.1998; 273:15559 -155564.
[21]Guipponi M, Scott HS, Kudoh J et al. Identification and characterization of a novel cyclic nucleotide phosphodiesterase gene (PDE9A) that maps to 21q22.3:alternative splicing of mRNA transcripts, genomic structure and sequence. [J] Hum Genet.1998; 103:386-392.
[22]Rentero C, Monfort A, Puigdomenech P. Identification and distribution of different mRNA variants produced by differential splicing in the human phosphodiesterase 9A gene. [J] Biochem Biophys Res Commun,2003; 301:686-692
[23]Loughney K, Martins TJ, Harris EA, Sadhu K, Hicks JB, Sonnenburg WK, Beavo JA, Ferguson K. Isolation and characterization of cDNAs corresponding to two human calcium, calmodulin-regulated,3-,5--cyclic nucleotide phosphodiesterases. [J] J Biol Chem.1996; 271:796-806.
[1]Rosselli M, Keller, P. J., Dubey, R. K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction. Hum.[J] Reprod. Update.,1998; 4:3-24.
[2]Tabata, M-aHaS. Nitric oxide and ovarian function. [J] Animal. Science. Journal., 2006;77:275-284.
[3]Pallares, P., Garcia-Fernandez, R.A., Criado, L.M., Letelier, C.A., Esteban, D., Fernandez-Toro, J.M., Flores, J.M., Gonzalez-Bulnes, A. Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J]Reproduction,2008; 136:573-579.
[4]Jablonka-Shariff A, Ravi S, Beltsos AN, Murphy LL, Olson LM. Abnormal Estrous Cyclicity after Disruption of Endothelial and Inducible Nitric Oxide Synthase in Mice. [J] Biol Reprod. 1999; 61,171-177.
[5]Gregg AR, Schauer A, Shi O, Liu Z, Lee CG, O'Brien WE.Limb reduction defects in endothelial nitric oxide synthase-deficient mice. [J] Am J Physiol.1998; 275:2319-2324.
[6]Pallares P, Garcia-Fernandez RA, Criado LM, Letelier CA, Esteban D, Fernandez-Toro JM, Flores JM, Gonzalez-Bulnes A.Disruption of the endothelial nitric oxide synthase gene affects ovulation, fertilization and early embryo survival in a knockout mouse model. [J] Reproduction,2008; 136:573-579.
[7]Jablonka-Shariff A, Olson LM. The Role of Nitric Oxide in Oocyte Meiotic Maturation and Ovulation:Meiotic Abnormalities of Endothelial Nitric Oxide Synthase Knock-Out Mouse Oocytes. [J] Endocrinology,1998; 139:2944-2954.
[8]Hefler LA, Gregg AR. Inducible and endothelial nitric oxide synthase:genetic background affects ovulation in mice. [J] Fertil Steril.2002; 77(1):147-51.
[9]Gyurko R, Leupen S, Huang PL.Deletion of Exon 6 of the Neuronal Nitric Oxide Synthase Gene in Mice Results in Hypogonadism and Infertility. [J] Endocrinology,2002; 143: 2767-2774.
[10]Development of Genetically Engineered Mice Lacking All Three Nitric Oxide Synthases [J] J Pharmacol Sci,2006; 102:147-154.
[11]Wei Zhang, Quanwei Wei, Zhengchao Wang, Wei Ding, Wei Wang, Fangxiong Shi, Cell-specific expression and immunolocalization of nitric oxide synthase isoforms and the related nitric oxide/cyclic GMP signaling pathway in the ovary of neonatal and immature rats. [J]J Zhejiang Univ-Sci B (Biomed & Biotechnol),2011;12:55-64.
[12]Shukovski L, Tsafriri A, The involvement of Nitric Oxide in the ovulatory process in the rat. [J]Endocrinology.1994; 135:2287-90.
[13]Effects of L-NAME and L-Arg on meiotic maturation ofmouse oocyte in vivo. [J] Journal of agricultural biotechnology,2003;11:291-294
[14]Flaws JA, Abbud R, Mann RJ, Nilson JH, Hirshfield AN. Chronically elevated luteinizing hormone depletes primordial follicles in the mouse ovary. [J Biol Reprod,1997; 57:1233-1237.
[15]Vitt UA, McGee EA, Hayashi M, Hsueh AJ. In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. [J] Endocrinology.2000; 141:3814-20.
[16]Schulz R, Panas DL, Catena R, Moncada S, Olley PM, Lopaschuk GD. The role of nitric oxide in cardiac depression induced by interleukin-1 beta and tumour necrosis factor-alpha. [J] Br J Pharmacol,1995;114:27-34.
[17]Wassarman PM, Albertini, D.F. The mammalian ovum. In:Knobil, E., Neill, J.D. (Eds.), [M] The Physiology of Reproduction.994.
[18]Elvin JA, Matzuk MM. Mouse models of ovarian failure. [J] Rev Reprod,1998; 3:183-95.
[19]Shi F, Stewart R L, Pere E, Chen JY, LaPolt PS Cell-specific expression and regulation of soluble guanylyl cyclase alpha and beta subunit in the rat ovary. [J] Bio Reprod,2004; 70: 1552-1561.
[20]Castrillon DH, Miao L1, Kollipara R, James WH, Ronald AD. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. [J]Science,2003; 301:215-218.
[21]John GB, Gallardo TD, Shirley LJ, Castrillon DH. Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. [J] Dev Biol,2008; 321:197-204.
[22]Engels K, Knauer SK, Loibl S, Fetz V, Harter P, Schweitzer A, Fisseler-Eckhoff A, Kommoss F, Hanker L, Nekljudova V, Hermanns I, Kleinert H, Mann W, du Bois A, Stauber RH. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas. [J] Cancer Res,2008; 68:5159-66.
[23]Borniquel S, Garcia-Quintans N, Valle I, Olmos Y, Wild B, Martinez-Granero F, Soria E, Lamas S, Monsalve M. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration. [J] Mol Cell Biol,2010; 30: 4035-44.
[24]Kim YM, Bombeck CA, Billiar TR. Nitric Oxide as a Bifunctional Regulator of Apoptosis. [J]Circ Res.1999; 19; 84:253-6.
[25]Chun SY, Hsueh AJ.Paracrine mechanisms of ovarian follicle apoptosis. [J] J Reprod Immunol. 1998; 39:63-75.
[1]Cantley LC. The phosphoinositide 3-kinase pathway [J]. Science,2002,296:1655-1657
[2]Cully M, You H, Levine AJ, et al. Beyond PTEN mutations:the PI3K pathway as an integrator of multiple inputs during tumorigenesis [J]. Nat Rev Cancer,2006,6:184-192
[3]Tran H, Brunet A, Griffith EC, et al. The many forks in FOXO's road [J]. Sci STKE 2003,172: re5
[4]Castrillon DH, Miao L1, Kollipara R, et al. Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a[J]. Science,2003,301:215-218
[5]Liu K, Raja reddy S, Liu L, et al. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway:New roles for an old timer [J]. Dev Biol,2006, 299:1-11
[6]John GB, Gallardo TD, Shirley LJ, et al. Foxo3 is a PI3Kdependent molecular switch controlling the initiation of oocyte growth [J].Developmental Biology,2008,321:197-204
[7]Rosselli M Keller P J, Dubey R K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction [J]. Hum Reprod. Update,1998,4:3-24
[8]Tabata, M-aHaS. Nitric oxide and ovarian function [J]. Animal. Science. Journal,2006, 77:275-284
[9]Engels K, Knauer SK, Loibl S, et al. NO signaling confers cytoprotectivity through the survivin network in ovarian carcinomas [J]. Cancer Res,2008,68:5159-5166
[10]Borniquel S, Garcia-Quintans N, Valle I, et al. Inactivation of Foxo3a and subsequent downregulation of PGC-1 alpha mediate nitric oxide-induced endothelial cell migration [J]. Mol Cell Biol,2010,30:4035-4044
[11]Yamamura Y, Lee WL, Inoue K, et al. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells [J] J Biol Chem,2006,281:5267-5276
[12]隋旭霞,罗丽莉,傅玉才.新生鼠卵巢FOXO3a表达水平与卵母细胞凋亡的相关性初步研[J]生殖与避孕,2006,26：515-519
[13]隋旭霞,傅玉才,罗丽莉.Foxo3a转录因子参与卵母细胞的凋亡[J].中国现代医学杂志,2007,17：1438-1441
[14]Matsumi H, Yano T, Koji T, et al. Expression and localization of inducible nitric oxide synthase in the rat ovary:a possible involvement of nitric oxide in the follicular development. Biochem. Biophys [J]. Res. Commun.,1998,243:67-72
[15]van den Hurk R, Zhao J. Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles [J]. Theriogenology,2005,63:1717-1751
[16]Ha KS, Kim K M, Kwon YG, et al.Nitric oxide prevents 6-hydroxydopamine-induced apoptosis in PC12 cells through cGMP-dependent PI3 kinase/Akt activation [J].FASEB J, 2003,17:1036-1047
[17]D. Jeannean Carver, Benjamin Gaston, Kimberly deRonde, Akt-Mediated Activation of HIF-1 in Pulmonary Vascular Endothelial Cells by S-Nitrosoglutathione [J].Am J Respir Cell Mol Biol,2007,37:255-263
[1]Kerr J F R, Wyllie A H, Curie A R. Apoptos is:a basic b iological phenom enonw ith w ide ranging im p licat ion in t issue k inet ics [J]. B r J Cancer,1972,26:239-257
[2]Escobar ML, Echeverria OM, Ortiz R, et al. Combined apoptosis and autophagy, the process that eliminates the oocytes of atretic follicles in immature rats [J]. Apoptosis,2008,13: 1253-1266
[3]Escobar ML, Echeverria OM, Sanchez-Sanchez L, et al. Analysis of different cell death processes of prepubertal rat oocytes in vitro [J]. Apoptosis,2010,15:511-526
[4]Basini G, Grasselli F, Ponderato N, et al. Lipid hydroperoxide and cGMP are not involved in nitric oxide inhibition of steroidogenesis in bovine granulosa cells [J]. Reprod Fertil Dev,2000,12:289-295
[5]Basini G, Baratta M, Ponderato N, et al. Is nitric oxide an autocrine modulator of bovine granulosa cell function? [J]. Reprod Fertil Dev,1998,10:471-478
[6]Pawan K. Dubey VT, Ram Pratap Singh, et al. Influence of nitric oxide on steroid synthesis, growth and apoptosis of Buffalo granulosa cells in vitro [J]. Anim. Sci,2011,24:1204-1210
[7]Sarkar S, Korolchuk VI, Renna M, et al. Complex inhibitory effects of nitric oxide on autophagy [J]. Mol Cell,2011,43:19-32
[8]Rabkin SW, Klassen SS. Nitric oxide differentially regulates the gene expression of caspase genes but not some autophagic genes [J]. Nitric Oxide,2007,16:339-347
[9]Rabkin SW. Nitric oxide-induced cell death in the heart:the role of autophagy [J]. Autophagy 2007,3:347-349
[10]Nicholson DW, Thornberry NA. Caspases:killer proteases [J]. Trends Biochem Sci,1997,22: 299-306
[11]Choi JY, Jo MW, Lee EY, et al. The role of autophagy in follicular development and atresia in rat granulosa cells. Fertil Steril.2010,93(8):2532-2537
[12]Rosselli M, Keller P J, Dubey R K. Role of nitric oxide in the biology, physiology and pathophysiology of reproduction [J]. Hum.Reprod. Update,1998,4:3-24
[13]Kim YM, Bombeck CA, Billiar TR. Nitric Oxide as a bifunctional regulator of apoptosis. [J].Circ Res,1999,19; 84:253-256
[14]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy [J]. Acta Pharmacol Sin,2011,32:1089-1099
[15]Boya P, Gonzalez-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis [J]. Mol Cell Biol,2005,25:1025-1040
[16]Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. [J] Acta Pharmacol Sin,2011; 32:1089-99.
[17]Boya P, Gonzalez-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, Metivier D, Meley D, Souquere S, Yoshimori T, Pierron G, Codogno P, Kroemer G. Inhibition of macroautophagy triggers apoptosis. [J] Mol Cell Biol,2005;25:1025-40.
[18]Jee B C, Kim S H, Moon S Y. Th e rol e of n it ric oxid e on apopt osis in human luteinized granul osa cell s. Immunocyt ochemi cal evidence. [J] Gynecol Obst et Invest,2003,56(3): 143-147.
[19]Chen Q, Yano T, Mat s umi H, et al. Cross-Talk between Fas/Fas ligand system and nitre oxide in the pathway subserv in granulosa cell apoptosi s:a possible regulatory mechanism for ovarian follicle at res ia. [J] Endocrinology,2005,146 (2):808-815.