卵巢特异性转录因子NOBOX、NANOS3、LHX8在卵巢早衰发病机制中的作用研究
|
摘要
第一章转录因子NOBOX敲除小鼠新生卵巢芯片结果分析
目的：Nobox是生殖细胞特异性转录调控因子，具有同源盒结构域，Nobox基因敲除雌鼠表现为初级卵泡发育障碍，出生后14天卵巢被纤维组织填充，导致不孕。Nobox作为同源盒蛋白家族成员，通过DNA-同源盒结构域相互作用调控下游基因的转录表达，在卵子早期发生过程发挥重要作用。研究目的是确定Nobox调控的下游基因，探讨Nobox对其他卵巢优势表达基因在分子水平的调节。
方法：通过基因芯片和实时定量PCR技术，分析Nobox基因敲除新生小鼠卵巢中基因的异常表达。
结果：基因芯片结果显示，Nobox敲除新生小鼠卵巢组织中，29个卵子优势表达基因表达水平较野生型降调≥5倍；5个卵子优势表达基因表达量升高5倍以上。以Oct4、Rspo2、Nalp4c、Jag1、Sall4、Stra8、Dmrt1、Tekt2、1700019D03Rik和Lin28作为候选基因，利用实时定量PCR技术验证基因芯片结果，候选基因在两种分析系统中表达变化趋势一致。
结论：敲除Nobox基因会不同程度的改变卵巢特异性基因的表达，Nobox是调节卵子发生的主导转录调控因子之一。通过对Nobox调控基因的研究将有助于我们充分认识生殖系统的基因表达调控及卵子发生异常疾病的发病机制。
第二章NOBOX基因突变与卵巢早衰的相关性研究
目的：同源盒基因NOBOX在卵子中特异性表达，在卵泡早期发育中发挥重要作用，是非综合型卵巢早衰的候选基因之一。本研究目的是探讨NOBOX基因突变与卵巢早衰发病机制的相关性。
方法：以就诊于Baylor College of Medicine的96名高加索卵巢早衰患者为研究对象，同时采集278例健康、卵巢功能正常的生育期女性外周血做为正常对照。利用直接测序法筛查卵巢早衰患者NOBOX基因突变情况，并利用凝胶迁移滞后实验探讨错义突变对DNA-蛋白质结合功能的影响。
结果：直接测序结果发现7个已知的单核苷酸多态和4个新发突变。新发突变包括2个单核苷酸多态、1同义突变和1个错义突变；其中p.Arg355His和p.Arg360Gln均发生在高度保守的同源盒结构域内。凝胶迁移滞后实验证实p.Arg355His突变蛋白结合DNA的能力明显降低，同时对野生型蛋白功能具有显性负效应。
结论：NOBOX基因突变是一部分卵巢早衰患者的致病原因。
第三章NANOS3、LHX8基因突变在卵巢早衰发病机制中的作用研究
第一部分NANOS3基因突变与卵巢早衰的相关性研究
目的：作为最早发现于果蝇的母源性基因，Nanos3具有编码RNA结合蛋白的功能，在生殖细胞向性腺迁移分化的过程中起重要作用。Nanos3基因敲除小鼠表现为卵巢萎缩、各级卵泡缺乏及不孕。人NANOS3基因在生殖细胞中特异性表达，并与小鼠Nanos3具有高度同源性，提示NANOS3可能是卵巢早衰(premature ovarian failure，POF)的候选基因。本研究通过对168例POF患者进行NANOS3基因突变筛查，以探讨NANOS3与POF病因的相关性。
方法：应用变性高效液相色谱分析(denaturing high-performance liquidchromatography，DHPLC)(WAVE System 3500 Transgenomic Ltd，Omaha，NE)对80例中国汉族及88例美国高加索人种POF患者NANOS3基因的两个外显子进行突变筛查，对DHPLC图形异常的PCR扩增产物则直接行DNA测序分析(ABI PRISM 310 AppliedBiosystems，Foster City，CA)。
结果：结果显示66例POF患者DHPLC图形出现双峰或对称性改变(汉族45例、高加索人种21例)，提示存在DNA序列变异。对PCR扩增产物进行测序分析发现第一外显子356位点发生碱基替换(c．356A＞G)，检索NCBI SNPs Database证实为已知同义单核苷酸多态(rs2016163)。其中杂合子、纯合子在汉族及高加索人种POF组发生频率分别为42.5％、13.7％和14.8％、9.1％。NANOS3其他编码序列区未发现致病突变。
结论：本研究没有在中国汉族和美国高加索人种卵巢早衰患者中发现NANOS3致病突变，因此推测在中国汉族和美国高加索人群中NANOS3基因突变与卵巢早衰没有明显的关系。
第二部分95例高加索卵巢早衰妇女LHX8突变分析研究
目的：LHX8(LIM homeobox 8)是一种在生殖细胞中特异性表达的转录调控因子，具有富含半胱氨酸-组氨酸的LIM结构域，在哺乳动物卵子发生过程中发挥重要作用。本研究通过筛查LHX8基因在95例高加索卵巢早衰患者中的突变情况，以探讨LHX8在人类卵巢早衰发病机制中作用。
方法：以95名就诊于Baylor college of medicine的美国高加索人种卵巢早衰患者为研究对象，同时收集94名卵巢功能正常的育龄期高加索女性外周血做为对照组，对LHX8编码序列进行直接测序分析。
结果：在内含子3和3’非翻译区(3’untranslated region，3’UTR)分别发现新发单核苷酸多态：c.769+10G＞T和c.1787A＞G。两种多态在POF患者和正常对照人群中的携带频率差别没有统计学意义(p＞0.05)。
结论：本研究结果提示LHX8基因突变不是美国高加索卵巢早衰妇女的常见病因。
Chapter I. Microarray analysis of newborn mouse ovaries lacking Nobox
OBJECTIVE: Nobox (newborn ovary homeobox gene), an oocyte-specific homeobox gene, plays a critical role during early folliculogenesis and represents a candidate gene for non-syndromic ovarian failure. The objective of this study is to investigate the downstream targets of Nobox.
METHODS: We compared the gene expression difference of newborn mouse ovaries between wild type and Nobox knockout using Affymetrix 430 2.0 microarray platform. We also quantified 10 genes that were potentially important during oogenesis using real-time PCR and discussed the possible roles of these genes in oocyte maturation.
RESULTS: Genes whose proteins were predicted to be secreted including Jagged 1 (Jag1) and respondin 2 (Rspo2) were down regulated in Nobox knockouts. Nalp4c, a gene that encoded protein involved in apoptotic and inflammatory signaling pathways, was down-regulated in Nobox~(-/-) ovaries. In addition, pluripotency associated genes, Oct4 and Sall4 were drastically down-regulated while stimulated by retinoic acid gene 8 (Stra8) which was involved in the retinoic acid metabolism, was among few up-regulated genes expressed in oocytes. Testes determining genes, including Dmrt1, Tekt2 and 1700019D03Rik were over-expressed in Nobox deficient ovaries.
CONCLUSION: Our findings indicate that Nobox is likely regulator of oocyte-specific gene expression, and suggest that transcription factors preferentially expressed in oocytes may repress male determining gene expression.
Chapter II. NOBOX Homeobox Mutations Cause Premature Ovarian Failure
OBJECTIVE: NOBOX (Newborn Ovary Homeobox gene), an oocyte-specific homeobox gene, plays a critical role during early folliculogenesis. Disruption of the murine Nobox gene causes non- syndromic ovarian failure in Nobox~(-/-) females. We investigate whether NOBOX has mutations causing premature ovarian failure (POF).
METHODS: We sequenced NOBOX gene in 96 Caucasian women with POF, followed by electrophoretic mobility shift assay (EMSA) to verify the effect of novel mutations on protein-DNA.
RESULTS: Seven known SNPs and 4 novel variations were discovered. Two of the latter, p. Arg355His and p. Arg360Gln, resides in the highly conserved homeodomain region. Using EMSA, we confirmed that mutation p. Arg355His in mouse decreases the affinity of homeodomain binding to the Nobox DNA binding elements, producing a dominant negative effect that disabled the DNA binding activity of wild type NOBOX.
CONCLUSION: Our findings suggest that NOBOX mutations contribute to a subset of women with POF.
Chapter III. Mutation analysis of NANOS3 and LHX8 in Womenwith Premature Ovarian Failure
Part I. Mutation Analysis of NANOS3 in 80 Chinese and 88 Caucasian Women with Premature Ovarian Failure
BACKGROUND AND OBJECTIVE: NANOS3 encodes an RNA binding protein and has a conserved function in germ cell development. Our objective was to investigate whether mutations in NANOS3 are present in Chinese and Caucasian women with premature ovarian failure (POF).
METHODS: Mutation Analysis of NANOS3 in 80 Chinese and 88 Caucasian women with POF were performed using denaturing high-performance liquid chromatography (DHPLC), followed by sequencing and restriction fragment length polymorphism (RFLP).
RESULTS: A known synonymous single nucleotide polymorphism (SNP) (rs 2016163) in exon 1 was identified through sequencing 80 Chinese and 88 Caucasian women with POF. No additional SNPs or mutations were found in exons encoding for NANOS3.
CONCLUSION: Our findings suggest that mutations in NANOS3 exons are rare in both Chinese and Caucasian women with POF.
Part II. Perturbations of LHX8 Do not Explain Caucasian Women with Premature Ovarian Failure
OBJECTIVE: LHX8 (LIM homeobox 8) encodes a LIM homeodomain transcriptional regulator preferentially expressed in germ cells and is a critical regulator of mammalian oogenesis. We investigated whether nucleotide changes are present in the LHX8 gene of Caucasian women with premature ovarian failure (POF) as compared to control women.
METHODS: Mutation of LHX8 was studied in 95 Caucasian women with POF and 94 controls by seqencing.
RESULTS: Two novel single nucleotide polymorphisms (SNPs) were discovered in intron 3 (c.769+10G>T) and 3' untranslated region (c.1787A>G) of the LHX8 gene. These polymorphisms were also found in controls with frequencies that were not statistically different from POF women.
CONCLUSION: Mutations in the LHX8 exons are uncommon in Caucasian women with POF.
目的：Nobox是生殖细胞特异性转录调控因子，具有同源盒结构域，Nobox基因敲除雌鼠表现为初级卵泡发育障碍，出生后14天卵巢被纤维组织填充，导致不孕。Nobox作为同源盒蛋白家族成员，通过DNA-同源盒结构域相互作用调控下游基因的转录表达，在卵子早期发生过程发挥重要作用。研究目的是确定Nobox调控的下游基因，探讨Nobox对其他卵巢优势表达基因在分子水平的调节。
方法：通过基因芯片和实时定量PCR技术，分析Nobox基因敲除新生小鼠卵巢中基因的异常表达。
结果：基因芯片结果显示，Nobox敲除新生小鼠卵巢组织中，29个卵子优势表达基因表达水平较野生型降调≥5倍；5个卵子优势表达基因表达量升高5倍以上。以Oct4、Rspo2、Nalp4c、Jag1、Sall4、Stra8、Dmrt1、Tekt2、1700019D03Rik和Lin28作为候选基因，利用实时定量PCR技术验证基因芯片结果，候选基因在两种分析系统中表达变化趋势一致。
结论：敲除Nobox基因会不同程度的改变卵巢特异性基因的表达，Nobox是调节卵子发生的主导转录调控因子之一。通过对Nobox调控基因的研究将有助于我们充分认识生殖系统的基因表达调控及卵子发生异常疾病的发病机制。
第二章NOBOX基因突变与卵巢早衰的相关性研究
目的：同源盒基因NOBOX在卵子中特异性表达，在卵泡早期发育中发挥重要作用，是非综合型卵巢早衰的候选基因之一。本研究目的是探讨NOBOX基因突变与卵巢早衰发病机制的相关性。
方法：以就诊于Baylor College of Medicine的96名高加索卵巢早衰患者为研究对象，同时采集278例健康、卵巢功能正常的生育期女性外周血做为正常对照。利用直接测序法筛查卵巢早衰患者NOBOX基因突变情况，并利用凝胶迁移滞后实验探讨错义突变对DNA-蛋白质结合功能的影响。
结果：直接测序结果发现7个已知的单核苷酸多态和4个新发突变。新发突变包括2个单核苷酸多态、1同义突变和1个错义突变；其中p.Arg355His和p.Arg360Gln均发生在高度保守的同源盒结构域内。凝胶迁移滞后实验证实p.Arg355His突变蛋白结合DNA的能力明显降低，同时对野生型蛋白功能具有显性负效应。
结论：NOBOX基因突变是一部分卵巢早衰患者的致病原因。
第三章NANOS3、LHX8基因突变在卵巢早衰发病机制中的作用研究
第一部分NANOS3基因突变与卵巢早衰的相关性研究
目的：作为最早发现于果蝇的母源性基因，Nanos3具有编码RNA结合蛋白的功能，在生殖细胞向性腺迁移分化的过程中起重要作用。Nanos3基因敲除小鼠表现为卵巢萎缩、各级卵泡缺乏及不孕。人NANOS3基因在生殖细胞中特异性表达，并与小鼠Nanos3具有高度同源性，提示NANOS3可能是卵巢早衰(premature ovarian failure，POF)的候选基因。本研究通过对168例POF患者进行NANOS3基因突变筛查，以探讨NANOS3与POF病因的相关性。
方法：应用变性高效液相色谱分析(denaturing high-performance liquidchromatography，DHPLC)(WAVE System 3500 Transgenomic Ltd，Omaha，NE)对80例中国汉族及88例美国高加索人种POF患者NANOS3基因的两个外显子进行突变筛查，对DHPLC图形异常的PCR扩增产物则直接行DNA测序分析(ABI PRISM 310 AppliedBiosystems，Foster City，CA)。
结果：结果显示66例POF患者DHPLC图形出现双峰或对称性改变(汉族45例、高加索人种21例)，提示存在DNA序列变异。对PCR扩增产物进行测序分析发现第一外显子356位点发生碱基替换(c．356A＞G)，检索NCBI SNPs Database证实为已知同义单核苷酸多态(rs2016163)。其中杂合子、纯合子在汉族及高加索人种POF组发生频率分别为42.5％、13.7％和14.8％、9.1％。NANOS3其他编码序列区未发现致病突变。
结论：本研究没有在中国汉族和美国高加索人种卵巢早衰患者中发现NANOS3致病突变，因此推测在中国汉族和美国高加索人群中NANOS3基因突变与卵巢早衰没有明显的关系。
第二部分95例高加索卵巢早衰妇女LHX8突变分析研究
目的：LHX8(LIM homeobox 8)是一种在生殖细胞中特异性表达的转录调控因子，具有富含半胱氨酸-组氨酸的LIM结构域，在哺乳动物卵子发生过程中发挥重要作用。本研究通过筛查LHX8基因在95例高加索卵巢早衰患者中的突变情况，以探讨LHX8在人类卵巢早衰发病机制中作用。
方法：以95名就诊于Baylor college of medicine的美国高加索人种卵巢早衰患者为研究对象，同时收集94名卵巢功能正常的育龄期高加索女性外周血做为对照组，对LHX8编码序列进行直接测序分析。
结果：在内含子3和3’非翻译区(3’untranslated region，3’UTR)分别发现新发单核苷酸多态：c.769+10G＞T和c.1787A＞G。两种多态在POF患者和正常对照人群中的携带频率差别没有统计学意义(p＞0.05)。
结论：本研究结果提示LHX8基因突变不是美国高加索卵巢早衰妇女的常见病因。
Chapter I. Microarray analysis of newborn mouse ovaries lacking Nobox
OBJECTIVE: Nobox (newborn ovary homeobox gene), an oocyte-specific homeobox gene, plays a critical role during early folliculogenesis and represents a candidate gene for non-syndromic ovarian failure. The objective of this study is to investigate the downstream targets of Nobox.
METHODS: We compared the gene expression difference of newborn mouse ovaries between wild type and Nobox knockout using Affymetrix 430 2.0 microarray platform. We also quantified 10 genes that were potentially important during oogenesis using real-time PCR and discussed the possible roles of these genes in oocyte maturation.
RESULTS: Genes whose proteins were predicted to be secreted including Jagged 1 (Jag1) and respondin 2 (Rspo2) were down regulated in Nobox knockouts. Nalp4c, a gene that encoded protein involved in apoptotic and inflammatory signaling pathways, was down-regulated in Nobox~(-/-) ovaries. In addition, pluripotency associated genes, Oct4 and Sall4 were drastically down-regulated while stimulated by retinoic acid gene 8 (Stra8) which was involved in the retinoic acid metabolism, was among few up-regulated genes expressed in oocytes. Testes determining genes, including Dmrt1, Tekt2 and 1700019D03Rik were over-expressed in Nobox deficient ovaries.
CONCLUSION: Our findings indicate that Nobox is likely regulator of oocyte-specific gene expression, and suggest that transcription factors preferentially expressed in oocytes may repress male determining gene expression.
Chapter II. NOBOX Homeobox Mutations Cause Premature Ovarian Failure
OBJECTIVE: NOBOX (Newborn Ovary Homeobox gene), an oocyte-specific homeobox gene, plays a critical role during early folliculogenesis. Disruption of the murine Nobox gene causes non- syndromic ovarian failure in Nobox~(-/-) females. We investigate whether NOBOX has mutations causing premature ovarian failure (POF).
METHODS: We sequenced NOBOX gene in 96 Caucasian women with POF, followed by electrophoretic mobility shift assay (EMSA) to verify the effect of novel mutations on protein-DNA.
RESULTS: Seven known SNPs and 4 novel variations were discovered. Two of the latter, p. Arg355His and p. Arg360Gln, resides in the highly conserved homeodomain region. Using EMSA, we confirmed that mutation p. Arg355His in mouse decreases the affinity of homeodomain binding to the Nobox DNA binding elements, producing a dominant negative effect that disabled the DNA binding activity of wild type NOBOX.
CONCLUSION: Our findings suggest that NOBOX mutations contribute to a subset of women with POF.
Chapter III. Mutation analysis of NANOS3 and LHX8 in Womenwith Premature Ovarian Failure
Part I. Mutation Analysis of NANOS3 in 80 Chinese and 88 Caucasian Women with Premature Ovarian Failure
BACKGROUND AND OBJECTIVE: NANOS3 encodes an RNA binding protein and has a conserved function in germ cell development. Our objective was to investigate whether mutations in NANOS3 are present in Chinese and Caucasian women with premature ovarian failure (POF).
METHODS: Mutation Analysis of NANOS3 in 80 Chinese and 88 Caucasian women with POF were performed using denaturing high-performance liquid chromatography (DHPLC), followed by sequencing and restriction fragment length polymorphism (RFLP).
RESULTS: A known synonymous single nucleotide polymorphism (SNP) (rs 2016163) in exon 1 was identified through sequencing 80 Chinese and 88 Caucasian women with POF. No additional SNPs or mutations were found in exons encoding for NANOS3.
CONCLUSION: Our findings suggest that mutations in NANOS3 exons are rare in both Chinese and Caucasian women with POF.
Part II. Perturbations of LHX8 Do not Explain Caucasian Women with Premature Ovarian Failure
OBJECTIVE: LHX8 (LIM homeobox 8) encodes a LIM homeodomain transcriptional regulator preferentially expressed in germ cells and is a critical regulator of mammalian oogenesis. We investigated whether nucleotide changes are present in the LHX8 gene of Caucasian women with premature ovarian failure (POF) as compared to control women.
METHODS: Mutation of LHX8 was studied in 95 Caucasian women with POF and 94 controls by seqencing.
RESULTS: Two novel single nucleotide polymorphisms (SNPs) were discovered in intron 3 (c.769+10G>T) and 3' untranslated region (c.1787A>G) of the LHX8 gene. These polymorphisms were also found in controls with frequencies that were not statistically different from POF women.
CONCLUSION: Mutations in the LHX8 exons are uncommon in Caucasian women with POF.
引文
1. Epifano O, Dean J (2002) Genetic control of early folliculogenesis in mice. Trends Endocrinol Metab 13: 169-173.
2. Grudzinskas JG (1995) Gametes: the oocyte. Cambridge University Press, Cambridge
3. Johnson J, Kanedo T, Pru JK, Tilly JL. (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428: 145-150.
4. Pangas SA, Rajkovic A (2006) Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update 12(1): 65-76.
5. Dean J. (2002) Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Rrprod Immunol 53: 171-180.
6. Rankin T, Talbot P, Lee E, Dean J (1999) Abnormal zonae pellucidae in mice lacking ZP 1 result in early embryonic loss. Development 126(17): 3847-3855.
7. Rankin TL, O'Brien M, Lee E, Wigglesworth K, Eppig J, Dean J (2001) Defective zonae pellucidae in Zp2-null mice disrupts folliculogenesis, fertility and development. Development 128(7): 1119-1126.
8. Rankin TL, Tong ZB, Castle PE, Lee E, Gore-Langton R, Nelson LM, Dean J (1998) Human ZP3 restores fertility in Zp3 null mice without affecting order-specific sperm binding. Development 125(13): 2415-2424.
9. McGrath SA, Esquela AF, Lee SJ (1995) Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9(1): 131-136.
10. Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, Boiani M, Lomeli H, Nagy A, McLaughlin K J, Scholer HR, Tomilin A (2004) Oct4 is required for primordial germ cell survival. EMBO Rep 5(11): 1078-1083.
11. Choi Y, Rajkovic A (2006) Genetics of early mammalian folliculogenesis. Cell Mol Life Sci 63(5): 579-590.
12. Suzumori N, Yan C, Matzuk MM, Rajkovic A (2002) Nobox is a homeobox-encoding gene preferentially expressed in primordial and growing oocytes. Mech Dev 111(1-2): 137-141.
13. Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM (2004) NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 305(5687): 1157-1159.
14. Banerjee-Basu S, Baxevanis AD (2001) Molecular evolution of the homeodomain family of transcription factors. Nucleic Acids Res 29 (15): 3258-3269.
15. Baltus AE, Menke DB, Hu YC, Goodheart ML, Carpenter AE, de Rooij DG, Page DC (2006) In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat Genet 38(12): 1430-1434.
16. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell 95(3): 379-391.
17. Pesce M, Wang X, Wolgemuth DJ, Scholer H (1998) Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev 71 (1-2): 89-98.
18. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lutkin T, Robson P, Lim B (2006) Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5fl. Nat Cell Biol 8(10): 1114-1123.
19. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, Patapoutian A, Hampton GM, Schultz PG, Hogenesch JB (2002) Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci 99(7): 4465-4470.
20. Richards M, Tan SP, Tan JH, Chan WK, Bongso A (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22(1): 51-64.
21. Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W (2004) R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7(4): 525-534.
22. Johnson J, Espinoza T, McGaughey RW, Rawls A, Wilson-Rawls J (2001) Notch pathway genes are expressed in mammalian ovarian follicles. Mech Dev 109(2): 355-361.
23. Vorontchikhina MA, Zimmermann RC, Shawber C J, Tang H, Kitajewski J (2005) Unique patterns of Notchl, Notch4 and Jaggedl expression in ovarian vessels during folliculogenesis and corpus luteum formation. Gene Expr Patterns 5(5): 701-709.
24. Tong ZB, Gold L, Pfeifer KE, Dorward H, Lee E, Bondy CA, Dean J, Nelson LM (2000) Mater, a maternal effect gene required for early embryonic development in mice. Nat Genet 26(3): 267-268.
25. Tong ZB, Bondy CA, Zhou J, Nelson LM (2002) A human homologue of mouse Mater, a maternal effect gene essential for early embryonic development. Hum Reprod 17(4): 903-911.
26. Tong ZB, Gold L, De Pol A, Vanevski K, Dorward H, Sena P, Palumbo C, Bondy CA, Nelson LM (2004) Developmental expression and subcellular localization of mouse MATER, an oocyte-specific protein essential for early development. Endocrinology 145(3): 1427-1434.
27. Raymond CS, Murphy MW, O'Sullivan MG, Bardwell VJ, Zarkower D (2000) Dmrtl, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 14(20): 2587-2595.
28. De Grandi A, Calvari V, Bertini V, Bulfone A, Peverali G, Camerino G, Borsani (3; Guioli S (2000) The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech Dev 90(2): 323-326.
29. Tanaka H, Iguchi N, Toyama Y, Kitamura K, Takahashi T, Kaseda K, Maekawa M, Nishimune Y (2004) Mice deficient in the axonemal protein Tektin-t exhibit male infertility and immotile-cilium syndrome due to impaired inner arm dynein function. Mol Cell Biol 24(18): 7958-7964.
30. Coulam CB, Adamson SC, Annegers JF (1986) Incidence of premature ovarian failure. Obstet Gynecol 67: 604-606.
31. Woad KJ, Watkins WJ, Prendergast D, Shelling AN (2006) The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol 46: 242-244.
32. Vegetti W, Grazia Tibiletti M, Testa G, de Lauretis Y, Alagna F, Castoldi E, Taborelli M, Motta T, Bolis PF, Dalpra L, Crosignani PG (1998) Inheritance in idiopathic premature ovarian failure: analysis of 71 cases. Hum Reprod 13: 1796-1800.
33. Simpson JL, Rajkovic A (1999) Ovarian differentiation and gonadal failure. Am J Med Genet 89: 186-200.
34. Simpson JL, Rajkovic A (2004) Germ cell failure and ovarian resistance: human genes and disorders. In: P. C. Leung EY, Adashi (eds) The Ovary. Elsevier Academic Press, 2nd Edition, pp 541-557.
35. Wittenberger, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM (2006) The FMR1 premutation and reproduction. Fertil Steril 87: 456-465.
36. Sullivan A. K, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, Yadav-Shah M, Sherman SL (2005) Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 20: 402-412.
37. Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82: 959-968.
38. Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Paniel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M (1999) New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol 13: 1844-1854.
39. Rannikko A, Pakarinen P, Manna PR, Beau I, Misrahi M, Aittomaki K, Huhtaniemi I (2002) Functional characterization of the human FSH receptor with an inactivating Ala189Val mutation. Mol Hum Reprod 8: 311-317.
40. Lacombe A, Lee H, Zahed L, Coucair M, Muller JM, Nelson SF, Salameh W, Vilain E (2006) Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. Am J Hum Genet 79: 113-119.
41. Gersak K, Harris SE, Smale WJ, Shelling AN (2004) A novel 30 bp deletion in the FOXL2 gene in a phenotypically normal woman with primary amenorrhoea: Case report. Hum Reprod 19: 2767-2770.
42. Nallathambi J, Moumne L, De Baere E, Beysen D, Usha K, Sundaresan P, Veitia RA (2006) A novel polyalanine expansion in FOXL2: the first evidence for a recessive form of the blepharophimosis syndrome (BPES) associated with ovarian dysfunction. Hum Genet 121: 107-112.
43. Di Pasquale E, Beck-Peccoz P, Persani L (2004) Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 75: 106-111.
44. Pangas S A, Li X, Robertson E J, Matzuk MM (2006) Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol 20: 1406-1422.
45. Racki W J, Richter J D (2006) CPEB controls oocyte growth and follicle development in the mouse. Development 133: 4527-4537.
46. Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, Sakari M, Takada I, Nakamura T, Metzger D, Chambon P, Kanno J, Yoshikawa H, Kato S (2006) Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci 103: 224-229.
47. Bodin L, Di Pasquale E, Fabre S, Bontoux M, Monget P, Persani L, Mulsant P (2007) A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology 148: 393-400.
48. Furukawa K, Iioka T, Morishita M, Yamaguchi A, Shindo H, Namba H, Yamashita S, Tsukazaki T (2002) Functional domains of paired-like homeoprotein Cartl and the relationship between dimerization and transcription activity. Genes Cells 7: 1135-1147.
49. Huntriss J, Hinkins M, Picton HM (2006) cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles. Mol Hum Reprod 12: 283-289.
50. Zhao XX, Suzumori N, Yamaguchi M, Suzumori K (2005) Mutational analysis of the homeobox region of the human NOBOX gene in Japanese women who exhibit premature ovarian failure. Fertil Steril 83: 1843-1844.
51. Banerjee-Basu S, Baxevanis AD (2001) Molecular evolution of the homeodomain family of transcription factors. Nucleic Acids Res 29: 3258-3269.
52. Choi Y, Rajkovic A (2006) Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5fl promoters. J Biol Chem 281: 35747-3756.
53. Kim DW, Kempf H, Chen RE, Lassar AB (2003) Characterization of Nkx3.2 DNA binding specificity and its requirement for somitic chondrogenesis. J Biol Chem 278: 27532-27539.
54. Bruun JA, Thomassen EI, Kristiansen K, Tylden G, Holm T, Mikkola I, Bjorkoy G, Johansen T (2005) The third helix of the homeodomain of paired class homeodomain proteins acts as a recognition helix both for DNA and protein interactions. Nucleic Acids Res 33: 2661-2675.
55. Koizumi K, Lintas C, Nirenberg M, Maeng JS, Ju JH, Mack JW, Gruschus JM, Odenwald WF, Ferretti JA (2003) Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure. Proc Natl Acad Sci 100: 3119-3124.
56. Ju JH, Maeng JS, Zemedkun M, Ahronovitz N, Mack JW, Ferretti JA, Gelmann EP, Gruschus JM (2006) Physical and functional interactions between the prostate suppressor homeoprotein NKX3.1 and serum response factor. J Mol Biol 360: 989-999.
57. Suzumori N, Pangas SA, Rajkovic A (2007) Candidate genes for premature ovarian failure. Curr Med Chem 14(3): 353-357.
58. Wang Z, Lin H. (2004) Nanos maintains germline stem cell self-renewal by preventing differentiation. Science 303(5666): 2016-2019.
59. Piccioni F, Zappavigna V, Verrotti AC (2005) A Cup Full of Functions. RNA Biol 2(4): 125-128.
60. Kalifa Y, Huang T, Rosen LN, Chatterjee S, Gavis ER (2006) Glorund, a Drosophila hnRNP F/H homolog, is an ovarian repressor of nanos translation. Dev Cell 10(3): 291-301.
61. Tres LL, Rosselot C, Kierszenbaum AL (2004) Primordial germ cells: what does it take to be alive? Mol Reprod Dev 68(1): 1-4.
62. Tsuda M, Sasaoka Y, Kiso M, Abe K, Haraguchi S, Kobayashi S, et al. (2003) Conserved role of nanos proteins in germ cell development. Science 301 (5637): 1239-1241.
63. Tong Y, Liao WX, Roy AC, Ng SC (2001) Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome. Horm Metab Res 33(4): 221-226.
64. Chen XN, Chen GA, Li MZ (2006) Follicular stimulating hormone receptor gene C566T mutation in premature ovarian failure. Zhonghua Fu Chan Ke Za Zhi (Chinese) 41(5): 315-318.
65. Suzuki A, Tsuda M, Saga Y (2007) Functional redundancy among Nanos proteins and a distinct role of Nanos2 during male germ cell development. Development 134(1): 77-83.
66. Kitanaka J, Takemura M, Matsumoto K, Moil T, Wanaka A (1998) Structure and chromosomal localization of a murine LIM/homeobox gene, Lhx8. Genomics 49(2): 307-309.
67. Pangas SA, Choi Y, Ballow D J, Zhao Y, Matzuk MM, Rajkovic A (2006) Oogenesis requires germ cell-specific transcriptional regulators Sohlhl and Lhx8. Proc Natl Acad Sci 103(21): 8090-95.
68. Hobert O, Westphal H (2000) Functions of LIM-homeobox genes. Trends Genet 16(2): 75-83.
69. Wassarman PM, Kinloch RA (1992) Gene expression during oogenesis in mice. Mutat Res 296(1-2): 3-15.
70. 70. McLaren A (2003) Primordial germ cells in the mouse. Dev Biol 262(1): 1-15.
71. Extavour CG, Akam M (2003) Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 130(24): 5869-5884.
72. Matzuk MM, Bums KH, Viveiros MM, Eppig JJ (2002) Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296(5576): 2178-2180.
73. Wright CS, Becket DL, Lin JS, Warner AE, Hardy K (2001) Stage-specific and differential expression of gap junctions in the mouse ovary: connexin-specific roles in follicular regulation. Reproduction 121(1): 77-88.
74. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM (1996) Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383(6600): 531-535.
75. Yan C, Wang P, DeMayo J, DeMayo F J, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM (2001) Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15(6): 854-866.
76. Verrijzer CP, Alkema MJ, van Weperen WW, Van Leeuwen HC, Strating M J, van der Vliet PC (1992) The DNA binding specificity of the bipartite POU domain and its subdomains. EMBO J 11(13): 4993-5003.
77. Kurosaka S, Eckardt S, McLaughlin KJ (2004) Pluripotent lineage definition in bovine embryos by Oct4 transcript localization. Biol Reprod 71 (5): 1578-1582.
78. Fuhrmann G, Chung AC, Jackson KJ, Hummelke G, Baniahmad A, Sutter J, Sylvester I, Scholer HR, Cooney AJ (2001) Mouse germline restriction of Oct4 expression by germ cell nuclear factor. Dev Cell 1(3): 377-387.
79. Pesce M, Gross MK, Scholer HR (1998) In line with our ancestors: Oct-4 and the mammalian germ. Bioessays 20 (9): 722-732.
80. Yeom YI, Fuhrmann G; Ovitt CE, Brehm A, Ohbo K, Gross M, Hubner K, Scholer HR (1996) Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 122(3): 881-894.
81. Rajpert-De Meyts E, Hanstein R, Jorgensen N, Graem N, Vogt PH, Skakkebaek NE (2004) Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod 19(6): 1338-1344.
82. Dean J (2002) Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol 53 (1-2): 171-180.
83. Rankin T, Talbot P, Lee E, Dean J (1999) Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss. Development 126(17): 3847-3855.
84. Rankin TL, O'Brien M, Lee E, Wigglesworth K, Eppig J, Dean J (2001) Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development. Development 128(7): 1119-1126.
85. Liang L, Soyal SM, Dean J (1997) FIG alpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Development 124(24): 4939-4947.
86. Bayne RA, Martins da Silva SJ, Anderson RA (2004) Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Mol Hum Reprod 10(6): 373-381.
87. Freiman RN, Albright SR, Zheng S, Sha WC, Hammer RE, Tjian R (2001) Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science 293(5537): 2084-2087.
88. Cocquet J, De Baere E, Gareil M, Pannetier M, Xia X, Fellous M, Veitia RA (2003) Structure, evolution and expression of the FOXL2 transcription unit. Cytogenet Genome Res 101(3-4): 206-211.
89. Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, Treier M (2004) The murine winged-helix transcription factor Fox12 is required for granulosa cell differentiation and ovary maintenance. Development 131(4): 933-942.
90. Dade S, Callebaut I, Mermillod P, Monger P (2003) Identification of a new expanding family of genes characterized by atypical LRR domains. Localization of a cluster preferentially expressed in oocyte. FEBS Lett 555(3): 533-538.
91. Minami N, Aizawa A, Ihara R, Miyamoto M, Ohashi A, Imai H (2003) Oogenesin is a novel mouse protein expressed in oocytes and early cleavage- stage embryos. Biol Reprod 69(5): 1736-1742.
92. Raverot G, Weiss J, Park SY, Hurley L, Jameson JL (2005) Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis Dev Biol 283(1): 215-225.
93. Rajkovic A, Yan C, Yan W, Klysik M, Matzuk MM (2002) Obox, a family of homeobox genes preferentially expressed in germ cells. Genomics 79(5): 711-717.
94. Yeh YJ, Choo K. B, Cheng WT, Li H (2002) Ohx is a homeobox-encoding gene preferentially expressed in mature oocytes. Mech Dev 117(1-2): 259-263.
2. Grudzinskas JG (1995) Gametes: the oocyte. Cambridge University Press, Cambridge
3. Johnson J, Kanedo T, Pru JK, Tilly JL. (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428: 145-150.
4. Pangas SA, Rajkovic A (2006) Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update 12(1): 65-76.
5. Dean J. (2002) Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Rrprod Immunol 53: 171-180.
6. Rankin T, Talbot P, Lee E, Dean J (1999) Abnormal zonae pellucidae in mice lacking ZP 1 result in early embryonic loss. Development 126(17): 3847-3855.
7. Rankin TL, O'Brien M, Lee E, Wigglesworth K, Eppig J, Dean J (2001) Defective zonae pellucidae in Zp2-null mice disrupts folliculogenesis, fertility and development. Development 128(7): 1119-1126.
8. Rankin TL, Tong ZB, Castle PE, Lee E, Gore-Langton R, Nelson LM, Dean J (1998) Human ZP3 restores fertility in Zp3 null mice without affecting order-specific sperm binding. Development 125(13): 2415-2424.
9. McGrath SA, Esquela AF, Lee SJ (1995) Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9(1): 131-136.
10. Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, Boiani M, Lomeli H, Nagy A, McLaughlin K J, Scholer HR, Tomilin A (2004) Oct4 is required for primordial germ cell survival. EMBO Rep 5(11): 1078-1083.
11. Choi Y, Rajkovic A (2006) Genetics of early mammalian folliculogenesis. Cell Mol Life Sci 63(5): 579-590.
12. Suzumori N, Yan C, Matzuk MM, Rajkovic A (2002) Nobox is a homeobox-encoding gene preferentially expressed in primordial and growing oocytes. Mech Dev 111(1-2): 137-141.
13. Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM (2004) NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science 305(5687): 1157-1159.
14. Banerjee-Basu S, Baxevanis AD (2001) Molecular evolution of the homeodomain family of transcription factors. Nucleic Acids Res 29 (15): 3258-3269.
15. Baltus AE, Menke DB, Hu YC, Goodheart ML, Carpenter AE, de Rooij DG, Page DC (2006) In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat Genet 38(12): 1430-1434.
16. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Scholer H, Smith A (1998) Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4 Cell 95(3): 379-391.
17. Pesce M, Wang X, Wolgemuth DJ, Scholer H (1998) Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev 71 (1-2): 89-98.
18. Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lutkin T, Robson P, Lim B (2006) Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5fl. Nat Cell Biol 8(10): 1114-1123.
19. Su AI, Cooke MP, Ching KA, Hakak Y, Walker JR, Wiltshire T, Orth AP, Vega RG, Sapinoso LM, Moqrich A, Patapoutian A, Hampton GM, Schultz PG, Hogenesch JB (2002) Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci 99(7): 4465-4470.
20. Richards M, Tan SP, Tan JH, Chan WK, Bongso A (2004) The transcriptome profile of human embryonic stem cells as defined by SAGE. Stem Cells 22(1): 51-64.
21. Kazanskaya O, Glinka A, del Barco Barrantes I, Stannek P, Niehrs C, Wu W (2004) R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis. Dev Cell 7(4): 525-534.
22. Johnson J, Espinoza T, McGaughey RW, Rawls A, Wilson-Rawls J (2001) Notch pathway genes are expressed in mammalian ovarian follicles. Mech Dev 109(2): 355-361.
23. Vorontchikhina MA, Zimmermann RC, Shawber C J, Tang H, Kitajewski J (2005) Unique patterns of Notchl, Notch4 and Jaggedl expression in ovarian vessels during folliculogenesis and corpus luteum formation. Gene Expr Patterns 5(5): 701-709.
24. Tong ZB, Gold L, Pfeifer KE, Dorward H, Lee E, Bondy CA, Dean J, Nelson LM (2000) Mater, a maternal effect gene required for early embryonic development in mice. Nat Genet 26(3): 267-268.
25. Tong ZB, Bondy CA, Zhou J, Nelson LM (2002) A human homologue of mouse Mater, a maternal effect gene essential for early embryonic development. Hum Reprod 17(4): 903-911.
26. Tong ZB, Gold L, De Pol A, Vanevski K, Dorward H, Sena P, Palumbo C, Bondy CA, Nelson LM (2004) Developmental expression and subcellular localization of mouse MATER, an oocyte-specific protein essential for early development. Endocrinology 145(3): 1427-1434.
27. Raymond CS, Murphy MW, O'Sullivan MG, Bardwell VJ, Zarkower D (2000) Dmrtl, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 14(20): 2587-2595.
28. De Grandi A, Calvari V, Bertini V, Bulfone A, Peverali G, Camerino G, Borsani (3; Guioli S (2000) The expression pattern of a mouse doublesex-related gene is consistent with a role in gonadal differentiation. Mech Dev 90(2): 323-326.
29. Tanaka H, Iguchi N, Toyama Y, Kitamura K, Takahashi T, Kaseda K, Maekawa M, Nishimune Y (2004) Mice deficient in the axonemal protein Tektin-t exhibit male infertility and immotile-cilium syndrome due to impaired inner arm dynein function. Mol Cell Biol 24(18): 7958-7964.
30. Coulam CB, Adamson SC, Annegers JF (1986) Incidence of premature ovarian failure. Obstet Gynecol 67: 604-606.
31. Woad KJ, Watkins WJ, Prendergast D, Shelling AN (2006) The genetic basis of premature ovarian failure. Aust N Z J Obstet Gynaecol 46: 242-244.
32. Vegetti W, Grazia Tibiletti M, Testa G, de Lauretis Y, Alagna F, Castoldi E, Taborelli M, Motta T, Bolis PF, Dalpra L, Crosignani PG (1998) Inheritance in idiopathic premature ovarian failure: analysis of 71 cases. Hum Reprod 13: 1796-1800.
33. Simpson JL, Rajkovic A (1999) Ovarian differentiation and gonadal failure. Am J Med Genet 89: 186-200.
34. Simpson JL, Rajkovic A (2004) Germ cell failure and ovarian resistance: human genes and disorders. In: P. C. Leung EY, Adashi (eds) The Ovary. Elsevier Academic Press, 2nd Edition, pp 541-557.
35. Wittenberger, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM (2006) The FMR1 premutation and reproduction. Fertil Steril 87: 456-465.
36. Sullivan A. K, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, Yadav-Shah M, Sherman SL (2005) Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 20: 402-412.
37. Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82: 959-968.
38. Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Paniel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M (1999) New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol 13: 1844-1854.
39. Rannikko A, Pakarinen P, Manna PR, Beau I, Misrahi M, Aittomaki K, Huhtaniemi I (2002) Functional characterization of the human FSH receptor with an inactivating Ala189Val mutation. Mol Hum Reprod 8: 311-317.
40. Lacombe A, Lee H, Zahed L, Coucair M, Muller JM, Nelson SF, Salameh W, Vilain E (2006) Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. Am J Hum Genet 79: 113-119.
41. Gersak K, Harris SE, Smale WJ, Shelling AN (2004) A novel 30 bp deletion in the FOXL2 gene in a phenotypically normal woman with primary amenorrhoea: Case report. Hum Reprod 19: 2767-2770.
42. Nallathambi J, Moumne L, De Baere E, Beysen D, Usha K, Sundaresan P, Veitia RA (2006) A novel polyalanine expansion in FOXL2: the first evidence for a recessive form of the blepharophimosis syndrome (BPES) associated with ovarian dysfunction. Hum Genet 121: 107-112.
43. Di Pasquale E, Beck-Peccoz P, Persani L (2004) Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 75: 106-111.
44. Pangas S A, Li X, Robertson E J, Matzuk MM (2006) Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol 20: 1406-1422.
45. Racki W J, Richter J D (2006) CPEB controls oocyte growth and follicle development in the mouse. Development 133: 4527-4537.
46. Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, Sakari M, Takada I, Nakamura T, Metzger D, Chambon P, Kanno J, Yoshikawa H, Kato S (2006) Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci 103: 224-229.
47. Bodin L, Di Pasquale E, Fabre S, Bontoux M, Monget P, Persani L, Mulsant P (2007) A novel mutation in the bone morphogenetic protein 15 gene causing defective protein secretion is associated with both increased ovulation rate and sterility in Lacaune sheep. Endocrinology 148: 393-400.
48. Furukawa K, Iioka T, Morishita M, Yamaguchi A, Shindo H, Namba H, Yamashita S, Tsukazaki T (2002) Functional domains of paired-like homeoprotein Cartl and the relationship between dimerization and transcription activity. Genes Cells 7: 1135-1147.
49. Huntriss J, Hinkins M, Picton HM (2006) cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles. Mol Hum Reprod 12: 283-289.
50. Zhao XX, Suzumori N, Yamaguchi M, Suzumori K (2005) Mutational analysis of the homeobox region of the human NOBOX gene in Japanese women who exhibit premature ovarian failure. Fertil Steril 83: 1843-1844.
51. Banerjee-Basu S, Baxevanis AD (2001) Molecular evolution of the homeodomain family of transcription factors. Nucleic Acids Res 29: 3258-3269.
52. Choi Y, Rajkovic A (2006) Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5fl promoters. J Biol Chem 281: 35747-3756.
53. Kim DW, Kempf H, Chen RE, Lassar AB (2003) Characterization of Nkx3.2 DNA binding specificity and its requirement for somitic chondrogenesis. J Biol Chem 278: 27532-27539.
54. Bruun JA, Thomassen EI, Kristiansen K, Tylden G, Holm T, Mikkola I, Bjorkoy G, Johansen T (2005) The third helix of the homeodomain of paired class homeodomain proteins acts as a recognition helix both for DNA and protein interactions. Nucleic Acids Res 33: 2661-2675.
55. Koizumi K, Lintas C, Nirenberg M, Maeng JS, Ju JH, Mack JW, Gruschus JM, Odenwald WF, Ferretti JA (2003) Mutations that affect the ability of the vnd/NK-2 homeoprotein to regulate gene expression: transgenic alterations and tertiary structure. Proc Natl Acad Sci 100: 3119-3124.
56. Ju JH, Maeng JS, Zemedkun M, Ahronovitz N, Mack JW, Ferretti JA, Gelmann EP, Gruschus JM (2006) Physical and functional interactions between the prostate suppressor homeoprotein NKX3.1 and serum response factor. J Mol Biol 360: 989-999.
57. Suzumori N, Pangas SA, Rajkovic A (2007) Candidate genes for premature ovarian failure. Curr Med Chem 14(3): 353-357.
58. Wang Z, Lin H. (2004) Nanos maintains germline stem cell self-renewal by preventing differentiation. Science 303(5666): 2016-2019.
59. Piccioni F, Zappavigna V, Verrotti AC (2005) A Cup Full of Functions. RNA Biol 2(4): 125-128.
60. Kalifa Y, Huang T, Rosen LN, Chatterjee S, Gavis ER (2006) Glorund, a Drosophila hnRNP F/H homolog, is an ovarian repressor of nanos translation. Dev Cell 10(3): 291-301.
61. Tres LL, Rosselot C, Kierszenbaum AL (2004) Primordial germ cells: what does it take to be alive? Mol Reprod Dev 68(1): 1-4.
62. Tsuda M, Sasaoka Y, Kiso M, Abe K, Haraguchi S, Kobayashi S, et al. (2003) Conserved role of nanos proteins in germ cell development. Science 301 (5637): 1239-1241.
63. Tong Y, Liao WX, Roy AC, Ng SC (2001) Absence of mutations in the coding regions of follicle-stimulating hormone receptor gene in Singapore Chinese women with premature ovarian failure and polycystic ovary syndrome. Horm Metab Res 33(4): 221-226.
64. Chen XN, Chen GA, Li MZ (2006) Follicular stimulating hormone receptor gene C566T mutation in premature ovarian failure. Zhonghua Fu Chan Ke Za Zhi (Chinese) 41(5): 315-318.
65. Suzuki A, Tsuda M, Saga Y (2007) Functional redundancy among Nanos proteins and a distinct role of Nanos2 during male germ cell development. Development 134(1): 77-83.
66. Kitanaka J, Takemura M, Matsumoto K, Moil T, Wanaka A (1998) Structure and chromosomal localization of a murine LIM/homeobox gene, Lhx8. Genomics 49(2): 307-309.
67. Pangas SA, Choi Y, Ballow D J, Zhao Y, Matzuk MM, Rajkovic A (2006) Oogenesis requires germ cell-specific transcriptional regulators Sohlhl and Lhx8. Proc Natl Acad Sci 103(21): 8090-95.
68. Hobert O, Westphal H (2000) Functions of LIM-homeobox genes. Trends Genet 16(2): 75-83.
69. Wassarman PM, Kinloch RA (1992) Gene expression during oogenesis in mice. Mutat Res 296(1-2): 3-15.
70. 70. McLaren A (2003) Primordial germ cells in the mouse. Dev Biol 262(1): 1-15.
71. Extavour CG, Akam M (2003) Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 130(24): 5869-5884.
72. Matzuk MM, Bums KH, Viveiros MM, Eppig JJ (2002) Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296(5576): 2178-2180.
73. Wright CS, Becket DL, Lin JS, Warner AE, Hardy K (2001) Stage-specific and differential expression of gap junctions in the mouse ovary: connexin-specific roles in follicular regulation. Reproduction 121(1): 77-88.
74. Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM (1996) Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383(6600): 531-535.
75. Yan C, Wang P, DeMayo J, DeMayo F J, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM (2001) Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15(6): 854-866.
76. Verrijzer CP, Alkema MJ, van Weperen WW, Van Leeuwen HC, Strating M J, van der Vliet PC (1992) The DNA binding specificity of the bipartite POU domain and its subdomains. EMBO J 11(13): 4993-5003.
77. Kurosaka S, Eckardt S, McLaughlin KJ (2004) Pluripotent lineage definition in bovine embryos by Oct4 transcript localization. Biol Reprod 71 (5): 1578-1582.
78. Fuhrmann G, Chung AC, Jackson KJ, Hummelke G, Baniahmad A, Sutter J, Sylvester I, Scholer HR, Cooney AJ (2001) Mouse germline restriction of Oct4 expression by germ cell nuclear factor. Dev Cell 1(3): 377-387.
79. Pesce M, Gross MK, Scholer HR (1998) In line with our ancestors: Oct-4 and the mammalian germ. Bioessays 20 (9): 722-732.
80. Yeom YI, Fuhrmann G; Ovitt CE, Brehm A, Ohbo K, Gross M, Hubner K, Scholer HR (1996) Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 122(3): 881-894.
81. Rajpert-De Meyts E, Hanstein R, Jorgensen N, Graem N, Vogt PH, Skakkebaek NE (2004) Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod 19(6): 1338-1344.
82. Dean J (2002) Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol 53 (1-2): 171-180.
83. Rankin T, Talbot P, Lee E, Dean J (1999) Abnormal zonae pellucidae in mice lacking ZP1 result in early embryonic loss. Development 126(17): 3847-3855.
84. Rankin TL, O'Brien M, Lee E, Wigglesworth K, Eppig J, Dean J (2001) Defective zonae pellucidae in Zp2-null mice disrupt folliculogenesis, fertility and development. Development 128(7): 1119-1126.
85. Liang L, Soyal SM, Dean J (1997) FIG alpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Development 124(24): 4939-4947.
86. Bayne RA, Martins da Silva SJ, Anderson RA (2004) Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Mol Hum Reprod 10(6): 373-381.
87. Freiman RN, Albright SR, Zheng S, Sha WC, Hammer RE, Tjian R (2001) Requirement of tissue-selective TBP-associated factor TAFII105 in ovarian development. Science 293(5537): 2084-2087.
88. Cocquet J, De Baere E, Gareil M, Pannetier M, Xia X, Fellous M, Veitia RA (2003) Structure, evolution and expression of the FOXL2 transcription unit. Cytogenet Genome Res 101(3-4): 206-211.
89. Schmidt D, Ovitt CE, Anlag K, Fehsenfeld S, Gredsted L, Treier AC, Treier M (2004) The murine winged-helix transcription factor Fox12 is required for granulosa cell differentiation and ovary maintenance. Development 131(4): 933-942.
90. Dade S, Callebaut I, Mermillod P, Monger P (2003) Identification of a new expanding family of genes characterized by atypical LRR domains. Localization of a cluster preferentially expressed in oocyte. FEBS Lett 555(3): 533-538.
91. Minami N, Aizawa A, Ihara R, Miyamoto M, Ohashi A, Imai H (2003) Oogenesin is a novel mouse protein expressed in oocytes and early cleavage- stage embryos. Biol Reprod 69(5): 1736-1742.
92. Raverot G, Weiss J, Park SY, Hurley L, Jameson JL (2005) Sox3 expression in undifferentiated spermatogonia is required for the progression of spermatogenesis Dev Biol 283(1): 215-225.
93. Rajkovic A, Yan C, Yan W, Klysik M, Matzuk MM (2002) Obox, a family of homeobox genes preferentially expressed in germ cells. Genomics 79(5): 711-717.
94. Yeh YJ, Choo K. B, Cheng WT, Li H (2002) Ohx is a homeobox-encoding gene preferentially expressed in mature oocytes. Mech Dev 117(1-2): 259-263.