维生素E对蜕膜化和妊娠的影响及相关机制的研究
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摘要
维生素E是一种脂溶性的营养元素,不能在体内合成,必须从食物中摄取。由于在生殖过程中起非常重要的作用,维生素E又称为生育酚,妊娠过程中缺乏维生素E可导致流产、早产、先兆子痫和胎儿宫内生长受限。其作为一种与生殖相关的营养因子,有研究发现它参与植入过程和胎盘形成过程,但是作用的确切时间和机制尚不清楚,仍需要进一步研究探讨。
我们首先利用维生素E缺乏的饲料建立了维生素E缺乏的大鼠不孕模型。一组在植入过程即交配后5.5天、6.5天和7.5天取材研究子宫内植入相关的基因的表达和定位情况,结果发现NF-κB、COX-2和a-TTP的表达情况发生变化,而HIF-1α的表达情况没有变化。另一组在植入过程中回补维生素E,观察其对维生素E缺乏大鼠妊娠结局的影响。结果发现在回补维生素E4小时后血浆中维生素E的浓度达到正常水平,同时发现随着回补时间的延后,回补维生素E对妊娠结局挽救的效果明显下降。
其次我们制备维生素E的转移蛋白α-TTP的抗体,研究α-TTP蛋白在人和大鼠的早孕组织中的表达定位情况,同时研究α-TTP蛋白在人月经周期子宫内膜中的表达变化以及大鼠人工诱导蜕膜过程中的表达情况。结果发现α-TTP蛋白在人和大鼠的子宫上皮细胞和血管内皮细胞表达,一旦子宫内膜发生蜕膜化,α-TTP会出现在蜕膜化的间质细胞,因此我们可以推断α-TTP是一个间质细胞蜕膜化的标识物。α-TTP在蜕膜化的间质细胞中的表达暗示维生素E参与植入过程的间质细胞蜕膜化。
最后,我们利用维生素E缺乏的假孕大鼠构建了自发蜕膜化的动物模型,同时检测了蜕膜化过程血清中E2和P4的水平。结果发现实验组50%以上的假孕大鼠的子宫出现了自发蜕膜化,在交配后5.5天实验组血清中E2的浓度将近是对照组的三倍,在交配后7.5天和9.5天E2浓度没有差异；血清中P4的浓度都没有明显变化。维生素E在体内主要是抗氧化作用,我们检测了子宫内的总抗氧化能力(T-AOC),进一步研究了和抗氧化或脂质过氧化相关的酶类。结果发现和对照相比,实验组中总抗氧化能力明显下降,同时脂质过氧化标识物MDA的含量、抗氧化酶SOD、CAT和GSH-Px的活性都发生了变化。
综上所述,我们利用不孕大鼠的回补实验探讨了维生素E参与植入过程的机制,明确了维生素E通过子宫肌层炎症影响大鼠的妊娠过程,最后导致不孕。同时我们检测了α-TTP在蜕膜化过程中的表达情况,明确提出了α-TTP是蜕膜化间质细胞的标识物,同时提示维生素E参与了蜕膜化的过程。最后我们利用低维生素E的大鼠构建了自发蜕膜化的模型,初步探讨了自发蜕膜化发生的机制,为后续的研究奠定了基础。
Vitamin E is a lipid-solution nutrient. It can not be self-synthesized by human bodies and should be offered by food. Because of its important role in fertility, vitamin E has been named tocopherol. Vitamin E deficiency during pregnancy may cause miscarriage, preterm birth, preeclampsia and intrauterine growth restriction. As a nutrilite relating with fertility, some researchs found that it participated in the implantation and placentation process. But its exact action time and mechanism has been not yet clear and need further study.
We firstly used vitamin E deficiency forage and established rat infertility model of vitamin E deficiency. Half of them were sampled, and then we detected the expression of the genes about the implantation process. Results showed the expression of NF-κB, COX-2and a-TTP had changes, and HIF-la did not change. The other half of the animals were used the experiment of vitamin E supplement. We wanted to know pregnancy outcome changed after vitamin E supplement in the implantation process. Results showed that the level of vitamin E in the plasma reached normal level after4h of vitamin E supplement. The rescue efficacy for pregnancy outcome got worse when supplement on7.5dpc (days post coitum) comparing with on5.5and6.5dpc.
Secondly we prepared anti-a-TTP (a-tocopherol transfer protein) antibody. Then we studied the localization of a-TTP in early pregnancy tissues of human and rat and the localization of a-TTP in the endometrium of human menstrual cycle and rat decidual tissue by oil-induced. In general, signals were detected in the luminal epithelia, glandular epithelium and vascular endothelium in human and rat uterus. Once endometrium was decidualized, a-TTP was also expressed in decidual stromal cells. It suggested that TTPA may serve as a useful immunohistochemical marker for decidualization. The localization of a-TTP in human and rat uterus suggested vitamin E participated in the decidualization of implantation.
Finally we established rat spontaneous decidual model by pseudopregnancy rat of vitamin E deficiency and detected the levels of E2and P4in the serum during the implantation process. We found that more than50%pseudopregnancy rat occured spontaneous decidualization. On5.5dpc the level of E2in vitamin E deficiency group almost3times comparing with the control group, and on7.5and9.5dpc the level of E2had no difference. The level of P4in the serum had no difference. The effect of vitamin E in the body is antioxidation, we detected T-AOC (total-anti-oxidizing-Cap-ability) in the uterus, and further studied enzymes of antioxidant or lipid peroxidation. Results showed that comparing with the control, T-AOC dramatically declined and lipid peroxidation marker MDA and the activity of SOD, CAT and GSH-Px all changed.
Taken together, we explored the role of vitamin E in the implantation process by supplying vitamin E for infertility rat. We confirmed that vitamin E impacted rat pregnancy process and caused its sterility by the inflammation of mesometrium. We detected the expression of a-TTP in the uterus of the decidual process. Then we proposed a-TTP is the marker of endometrial stromal cell decidualization. It also suggested vitamin E participated in the decidual process. At last we established spontaneous decidual model by the rat of vitamin E deficiency and studied the mechanism of spontaneous decidualization. This study has laid the groundwork for the relevant future studies.
我们首先利用维生素E缺乏的饲料建立了维生素E缺乏的大鼠不孕模型。一组在植入过程即交配后5.5天、6.5天和7.5天取材研究子宫内植入相关的基因的表达和定位情况,结果发现NF-κB、COX-2和a-TTP的表达情况发生变化,而HIF-1α的表达情况没有变化。另一组在植入过程中回补维生素E,观察其对维生素E缺乏大鼠妊娠结局的影响。结果发现在回补维生素E4小时后血浆中维生素E的浓度达到正常水平,同时发现随着回补时间的延后,回补维生素E对妊娠结局挽救的效果明显下降。
其次我们制备维生素E的转移蛋白α-TTP的抗体,研究α-TTP蛋白在人和大鼠的早孕组织中的表达定位情况,同时研究α-TTP蛋白在人月经周期子宫内膜中的表达变化以及大鼠人工诱导蜕膜过程中的表达情况。结果发现α-TTP蛋白在人和大鼠的子宫上皮细胞和血管内皮细胞表达,一旦子宫内膜发生蜕膜化,α-TTP会出现在蜕膜化的间质细胞,因此我们可以推断α-TTP是一个间质细胞蜕膜化的标识物。α-TTP在蜕膜化的间质细胞中的表达暗示维生素E参与植入过程的间质细胞蜕膜化。
最后,我们利用维生素E缺乏的假孕大鼠构建了自发蜕膜化的动物模型,同时检测了蜕膜化过程血清中E2和P4的水平。结果发现实验组50%以上的假孕大鼠的子宫出现了自发蜕膜化,在交配后5.5天实验组血清中E2的浓度将近是对照组的三倍,在交配后7.5天和9.5天E2浓度没有差异；血清中P4的浓度都没有明显变化。维生素E在体内主要是抗氧化作用,我们检测了子宫内的总抗氧化能力(T-AOC),进一步研究了和抗氧化或脂质过氧化相关的酶类。结果发现和对照相比,实验组中总抗氧化能力明显下降,同时脂质过氧化标识物MDA的含量、抗氧化酶SOD、CAT和GSH-Px的活性都发生了变化。
综上所述,我们利用不孕大鼠的回补实验探讨了维生素E参与植入过程的机制,明确了维生素E通过子宫肌层炎症影响大鼠的妊娠过程,最后导致不孕。同时我们检测了α-TTP在蜕膜化过程中的表达情况,明确提出了α-TTP是蜕膜化间质细胞的标识物,同时提示维生素E参与了蜕膜化的过程。最后我们利用低维生素E的大鼠构建了自发蜕膜化的模型,初步探讨了自发蜕膜化发生的机制,为后续的研究奠定了基础。
Vitamin E is a lipid-solution nutrient. It can not be self-synthesized by human bodies and should be offered by food. Because of its important role in fertility, vitamin E has been named tocopherol. Vitamin E deficiency during pregnancy may cause miscarriage, preterm birth, preeclampsia and intrauterine growth restriction. As a nutrilite relating with fertility, some researchs found that it participated in the implantation and placentation process. But its exact action time and mechanism has been not yet clear and need further study.
We firstly used vitamin E deficiency forage and established rat infertility model of vitamin E deficiency. Half of them were sampled, and then we detected the expression of the genes about the implantation process. Results showed the expression of NF-κB, COX-2and a-TTP had changes, and HIF-la did not change. The other half of the animals were used the experiment of vitamin E supplement. We wanted to know pregnancy outcome changed after vitamin E supplement in the implantation process. Results showed that the level of vitamin E in the plasma reached normal level after4h of vitamin E supplement. The rescue efficacy for pregnancy outcome got worse when supplement on7.5dpc (days post coitum) comparing with on5.5and6.5dpc.
Secondly we prepared anti-a-TTP (a-tocopherol transfer protein) antibody. Then we studied the localization of a-TTP in early pregnancy tissues of human and rat and the localization of a-TTP in the endometrium of human menstrual cycle and rat decidual tissue by oil-induced. In general, signals were detected in the luminal epithelia, glandular epithelium and vascular endothelium in human and rat uterus. Once endometrium was decidualized, a-TTP was also expressed in decidual stromal cells. It suggested that TTPA may serve as a useful immunohistochemical marker for decidualization. The localization of a-TTP in human and rat uterus suggested vitamin E participated in the decidualization of implantation.
Finally we established rat spontaneous decidual model by pseudopregnancy rat of vitamin E deficiency and detected the levels of E2and P4in the serum during the implantation process. We found that more than50%pseudopregnancy rat occured spontaneous decidualization. On5.5dpc the level of E2in vitamin E deficiency group almost3times comparing with the control group, and on7.5and9.5dpc the level of E2had no difference. The level of P4in the serum had no difference. The effect of vitamin E in the body is antioxidation, we detected T-AOC (total-anti-oxidizing-Cap-ability) in the uterus, and further studied enzymes of antioxidant or lipid peroxidation. Results showed that comparing with the control, T-AOC dramatically declined and lipid peroxidation marker MDA and the activity of SOD, CAT and GSH-Px all changed.
Taken together, we explored the role of vitamin E in the implantation process by supplying vitamin E for infertility rat. We confirmed that vitamin E impacted rat pregnancy process and caused its sterility by the inflammation of mesometrium. We detected the expression of a-TTP in the uterus of the decidual process. Then we proposed a-TTP is the marker of endometrial stromal cell decidualization. It also suggested vitamin E participated in the decidual process. At last we established spontaneous decidual model by the rat of vitamin E deficiency and studied the mechanism of spontaneous decidualization. This study has laid the groundwork for the relevant future studies.
引文
[1]Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction[J]. Science,1922,56:650-651.
[2]Olcott HS, Emerson OH. Antioxidants and the autoxidantion of fats. Ⅸ. The antioxidant properties of the tocopherol[J]. J Am Chem Soc,1937,59:1008-1009.
[3]Brigelius-Flohe R, Kelly FJ, Salonen JT, et al. The European perspective on vitamin E:current knowledge and future research[J]. Am J Clin Nutr,2002,76(4):703-16.
[4]Kelly F, Meydani M, Packer L. Vitamin E and Health[J]. Annals of the New York Academy of Sciences,2004,1031:463.
[5]Evans HM, Burr GO. The Anti-Sterility Vitamine Fat Soluble E[J]. Proc Natl Acad SciUSA,1925,11(6):334-341.
[6]Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more[J]. Free Radic Biol Med,2007,43(1):4-15.
[7]Jishage K, Arita M, Igarashi K, et al. Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice[J]. J Biol Chem,2001,276(3):1669-1672.
[8]Kaempf-Rotzoll DE, Igarashi K, Aoki J, et al. Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus [J]. Biol Reprod,2002,67(2):599-604.
[9]Jishage K, Tachibe T, Ito T, et al. Vitamin E is essential for mouse placentation but not for embryonic development itself[J]. Biol Reprod,2005,73(5):983-987.
[10]Debier C. Vitamin E during pre- and postnatal periods[J]. Vitam Horm,2007, 76:357-373.
[11]Hacquebard M, Carpentier YA. Vitamin E:Absorption, plasma transport and cell uptake[J]. Curr Opin Clin Nutr Metab Care,2005,8(2):133-138.
[12]Kaliora AC, Dedoussis GV, Schmidt H. Dietary antioxidants in preventing atherogenesis[J]. Atherosclerosis,2006,187(1):1-17.
[13]Azzi A. Molecular mechanism of alpha-tocopherol action[J]. Free Radic Biol Med, 2007,43(1):16-21.
[14]Zingg JM, Meydani M, Azzi A. a-Tocopheryl phosphate--an activated form of vitamin E important for angiogenesis and vasculogenesis[J]? Biofactors,2012, 38(1):24-33.
[15]Molano A, Meydani SN. Vitamin E, signalosomes and gene expression in T cells[J]. Mol Aspects Med,2012,33(1):55-62.
[16]Rimbach G, Moehring J, Huebbe P, et al. Gene-regulatory activity of alpha-tocopherol[J]. Molecules,2010,15(3):1746-1761.
[17]Galli F, Azzi A. Present trends in vitamin E research[J]. Biofactors,2010, 36(1):33-42.
[18]Banerjee S, Chambers AE, Campbell S. Is vitamin E a safe prophylaxis for preeclampsia[J]? Am J Obstet Gynecol,2006,194(5):1228-1233.
[19]Shaw HM, Huang CJ. Liver alpha-tocopherol transfer protein and its mRNA are differentially altered by dietary vitamin E deficiency and protein insufficiency in rats[J]. J Nutr,1998,128(12):2348-2354.
[20]Mustacich DJ, Leonard SW, Devereaux MW, Sokol RJ, Traber MG. Alpha-tocopherol regulation of hepatic cytochrome P450s and ABC transporters in rats[J]. Free Radic Biol Med,2006,41:1069-1078.
[21]Li YF, Xu XB, Chen XH, et al. The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice[J]. Hum Reprod,2012,27(7):2096-2106.
[22]Daikoku T, Matsumoto H, Gupta RA, et al. Expression of hypoxia-inducible factors in the peri-implantation mouse uterus is regulated in a cell-specific and ovarian steroid hormone-dependent manner. Evidence for differential function of HIFs during early pregnancy [J]. J Biol Chem,2003,278(9):7683-7691.
[23]Zhang B, Tanaka J, Yang L, et al. Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1[J].Neuroscience,2004,126(2):433-440.
[24]Xu JP, Yin YP, Zhou XQ. Effect of vitamin E on reproductive function in the mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Toxicol Ind Health,2008, 24(9):595-601.
[25]Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes[J]. Am J Clin Nutr,2005,81(4):736-745.
[26]Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease:a systematic review[J]. J Intern Med,2002,251(5):372-392.
[27]Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis:high-dosage vitamin E supplementation may increase all-cause mortality[J]. Ann Intern Med,2005, 142(1):37-46.
[28]Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer:a randomized controlled trial[J]. JAMA,2005, 293(11):1338-1347.
[29]Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention:systematic review and meta-analysis[J]. JAMA,2007,297(8):842-857.
[30]Chappell LC, Seed PT, Kelly FJ, et al. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function[J]. Am J Obstet Gynecol,2002,187(3):777-784.
[31]Ye X, Hama K, Contos JJ, et al. LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing[J]. Nature,2005,435(7038):104-108.
[32]Azzi A, Gysin R, Kempna P, et al. Vitamin E mediates cell signaling and regulation of gene expression[J]. Ann N Y Acad Sci,2004,1031:86-95.
[33]Ouahchi K, Arita M, Kayden H, et al. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein[J]. Nat Genet,1995, 9(2):141-145.
[34]Copp RP, Wisniewski T, Hentati F, et al. Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders[J]. Brain Res,1999, 822(1-2):80-87.
[35]Gohil K, Godzdanker R, O'Roark E, et al. Alpha-tocopherol transfer protein deficiency in mice causes multi-organ deregulation of gene networks and behavioral deficits with age [J]. Ann N Y Acad Sci,2004,1031:109-126.
[36]Hosomi A, Goto K, Kondo H, et al. Localization of alpha-tocopherol transfer protein in rat brain[J]. Neurosci Lett,1998,256(3):159-162.
[37]Kaempf-Rotzoll DE, Horiguchi M, Hashiguchi K, et al. Human placental trophoblast cells express alpha-tocopherol transfer protein[J]. Placenta,2003,24(5):439-444.
[38]Tabanelli S, Tang B, Gurpide E. In vitro decidualization of human endometrial stromal cells[J]. J Steroid Biochem Mol Biol,1992,42(3-4):337-344.
[39]Telgmann R, Gellersen B. Marker genes of decidualization:activation of the decidual prolactin gene[J]. Hum Reprod Update,1998,4(5):472-479.
[40]Tseng L, Mazella J. Endometrial cell specific gene activation during implantation and early pregnancy[J]. Front Biosci,2002,7:d1566-1574.
[41]Chen GT, Getsios S, MacCalman CD. Cadherin-11 is a hormonally regulated cellular marker of decidualization in human endometrial stromal cells [J]. Mol Reprod Dev, 1999,52(2):158-165.
[42]Xu XB, He B, Wang JD. Menstrual-like changes in mice are provoked through the pharmacologic withdrawal of progesterone using mifepristone following induction of decidualization[J]. Hum Reprod,2007,22(12):3184-3191.
[43]Finn CA, Keen PM. The induction of deciduomata in the rat[J]. J Embryol Exp Morphol,1963,11:673-682.
[44]Hwang SY, Greenway AL, McMullen GL, et al. Detection of cells producing murine interferon-alpha using antipeptide antibodies [J]. Immunol Cell Biol,1994, 72(3):234-240.
[45]Traber MG, Arai H. Molecular mechanisms of vitamin E transport[J]. Annu Rev Nutr,1999,19:343-355.
[46]Robert BR, Janos Z, John WS, et al. Handbook of vitamins, third Edition (M). New York:Marcel Dekker,2001:170-171.
[47]Rotzoll DE, Scherling R, Etzl R, et al. Immunohistochemical localization of alpha-tocopherol transfer protein and lipoperoxidation products in human first-trimester and term placenta[J]. Eur J Obstet Gynecol Reprod Biol,2008, 140(2):183-191.
[48]Muller-Schmehl K, Beninde J, Finckh B, et al. Localization of alpha-tocopherol transfer protein in trophoblast, fetal capillaries' endothelium and amnion epithelium of human term placenta[J]. Free Radic Res,2004,38(4):413-420.
[49]Das P, Chowdhury M. Vitamin E-deficiency induced changes in ovary and uterus[J]. Mol Cell Biochem,1999,198(1-2):151-156.
[50]Hempstock J, Cindrova-Davies T, Jauniaux E, et al. Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy:a morphological and immunohistochemical study[J]. Reprod Biol Endocrinol,2004,2:58.
[51]Arita M, Sato Y, Miyata A, et al. Human alpha-tocopherol transfer protein:cDNA cloning, expression and chromosomal localization [J]. Biochem J,1995,306(Pt 2):437-443.
[52]Sugino N. The role of oxygen radical-mediated signaling pathways in endometrial function[J]. Placenta,2007,28 Suppl A:S133-136.
[53]Riley JC, Behrman HR. Oxygen radicals and reactive oxygen species in reproduction[J]. Proc Soc Exp Biol Med,1991,198(3):781-791.
[54]Finn CA, Pope M. Vascular and cellular changes in the decidualized endometrium of the ovariectomized mouse following cessation of hormone treatment:a possible model for menstruation[J]. J Endocrinol,1984,100(3):295-300.
[55]Rogers PA. Structure and function of endometrial blood vessels[J]. Hum Reprod Update,1996,2(1):57-62.
[56]Rasweiler JJ 4th. Spontaneous decidual reactions and menstruation in the black mastiff bat,Molossus ater[J].Am J Anat,1991,191(1):1-22.
[57]Finn CA. Menstruation:a nonadaptive consequence of uterine evolution[J]. Q Rev Biol,1998,73(2):163-173.
[58]Ramathal CY, Bagchi IC, Taylor RN, et al. Endometrial decidualization:of mice and men[J]. Semin Reprod Med,2010,28(1):17-26.
[59]Mihm M, Gangooly S, Muttukrishna S. The normal menstrual cycle in women[J]. Anim Reprod Sci,2011,124(3-4):229-236.
[60]Terkel J. Neuroendocrine processes in the establishment of pregnancy and pseudopregnancy in rats[J]. Psychoneuroendocrinology,1988,13(1-2):5-28.
[61]Schlafke S, Welsh AO, Enders AC. Penetration of the basal lamina of the uterine luminal epithelium during implantation in the rat[J]. Anat Rec,1985,212(1):47-56.
[62]Evans HM. Spontaneous deciduomata in pseudopregnancy with low vitamin E[J]. Am J Physiol,1928,85 (1):149-153.
[63]Coppola JA, Ball JL, Brown HW. The incidence of spontaneous deciduomata in pseudopropregnant rats[J]. J Reprod Fertil,1966,12(2):389-390.
[64]Brosens JJ, Gellersen B. Something new about early pregnancy:decidual biosensoring and natural embryo selection[J]. Ultrasound Obstet Gynecol,2010, 36(1):1-5.
[65]Teklenburg G, Salker M, Heijnen C, et al. The molecular basis of recurrent pregnancy loss:impaired natural embryo selection[J]. Mol Hum Reprod,2010, 16(12):886-895.
[66]Shaikh AA. Estrone and estradiol levels in the ovarian venous blood from rats during the estrous cycle and pregnancy[J]. Biol Reprod,1971,5(3):297-307.
[67]Finn CA. Endocrine control of endometrial sensitivity during the induction of the decidual cell reaction in the mouse[J]. J Endocrinol,1966,36(3):239-248.
[68]Shelesnyak MC, Kraicer PF, Zeilmaker GH. Studies on the mechanism of decidualization[J]. I. Acta Endocrinol,1963,42 (2) 225-232.
[69]Hatamoto LK, Baptista Sobrinho CA, Nichi M, et al. Effects of dexamethasone treatment (to mimic stress) and Vitamin E oral supplementation on the spermiogram and on seminal plasma spontaneous lipid peroxidation and antioxidant enzyme activities in dogs[J]. Theriogenology,2006,66(6-7):1610-1614.
[70]Sugino N, Shimamura K, Takiguchi S, et al. Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy[J]. Hum Reprod,1996, 11(5):1073-1078.
[71]Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species[J]. Biochemistry (Mosc),2005,70(2):200-214.
[1]Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction[J]. Science,1922,56(1458):650-651.
[2]Ng MH, Choo YM, Ma AN, et al. Separation of vitamin E (tocopherol, tocotrienol, and tocomonoenol) in palm oil[J]. Lipids,2004,39(10):1031-1035.
[3]Yamamoto Y, Fujisawa A, Hara A, et al. An unusual vitamin E constituent (alpha-tocomonoenol) provides enhanced antioxidant protection in marine organisms adapted to cold-water environments [J]. Proc Natl Acad Sci U S A,2001, 98(23):13144-13148.
[4]Gianello R, Libinaki R, Azzi A, et al. Alpha-tocopheryl phosphate:a novel, natural form of vitamin E[J]. Free Radic Biol Med,2005,39(7):970-976.
[5]Munteanu A, Zingg JM, Ogru E, et al. Modulation of cell proliferation and gene expression by alpha-tocopheryl phosphates:relevance to atherosclerosis and inflammation[J]. Biochem Biophys Res Commun,2004,318(1):311-316.
[6]Negis Y, Zingg JM, Ogru E, et al. On the existence of cellular tocopheryl phosphate, its synthesis, degradation and cellular roles:a hypothesis[J]. IUBMB Life,2005, 57(1):23-25.
[7]Niki E. Role of vitamin E as lipid-soluble peroxyl radical scavenger:In vitro and in vivo evidence[J]. Free Radic Biol Med,2013, doi:10.1016/j.freeradbiomed. 2013.03.022.
[8]Wong RS, Radhakrishnan AK. Tocotrienol research:past into present[J]. Nutr Rev, 2012,70(9):483-490.
[9]Zingg JM, Meydani M, Azzi A. a-Tocopheryl phosphate--an activated form of vitamin E important for angiogenesis and vasculogenesis? [J]. Biofactors,2012, 38(1):24-33.
[10]Molano A, Meydani SN. Vitamin E, signalosomes and gene expression in T cells[J]. Mol Aspects Med,2012,33(1):55-62.
[11]Rimbach G, Moehring J, Huebbe P, et al. Gene-regulatory activity of alpha-tocopherol[J]. Molecules,2010,15(3):1746-1761.
[12]Galli F, Azzi A. Present trends in vitamin E research[J]. Biofactors,2010,36(1): 33-42.
[13]Lodge JK. Vitamin E bioavailability in humans[J]. J Plant Physiol,2005,162(7): 790-796.
[14]Schenker S, Yang Y, Perez A et al. Antioxidant transport by the human placenta[J]. Clin Nutr,1998,17(4):159-167.
[15]Jauniaux E, Cindrova-Davies T, Johns J, et al. Distribution and transfer pathways of antioxidant molecules inside the first trimester human gestational sac[J]. J Clin Endocrinol Metab,2004,89(3):1452-1458.
[16]Kaempf-Rotzoll DE, Horiguchi M, Hashiguchi K, et al. Human placental trophoblast cells express alpha-tocopherol transfer protein[J]. Placenta,2003,24(5):439-444.
[17]Muller-Schmehl K, Beninde J, Finckh B, et al. Localization of alpha-tocopherol transfer protein in trophoblast, fetal capillaries'endothelium and amnion epithelium of human term placenta[J]. Free Radic Res,2004,38(4):413-420
[18]Kaempf-Rotzoll, DE, Igarashi K, Aoki J, et al. Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus[J]. Biol Reprod,2002,67(2):599-604.
[19]Browne RW, Bloom MS, Shelly WB, et al. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF[J]. J Assist Reprod Genet,2009,26(11-12):557-560.
[20]Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases[J]. Hum Fertil (Camb),2009,12(4):198-203.
[21]Turner SW, Campbell D, Smith N, et al. Associations between fetal size, maternal {alpha}-tocopherol and childhood asthma[J]. Thorax,2010,65(5):391-397.
[22]McLernon PC, Wood LG, Murphy VE, et al. Circulating antioxidant profile of pregnant women with asthma[J]. Clin Nutr,2012,31(1):99-107.
[23]Vieira-Filho LD, Cabral EV, Santos FT, et al. Alpha-tocopherol prevents intrauterine undernutrition-induced oligonephronia in rats[J]. Pediatr Nephrol,2011, 26(11):2019-2029.
[24]Miller GW, Ulatowski L, Labut EM, et al. The a-tocopherol transfer protein is essential for vertebrate embryogenesis[J]. PLoS One,2012,7(10):e47402. doi: 10.1371
[25]Kramer MS, Kahn SR, Platt RW, et al. Antioxidant vitamins, long-chain fatty acids, and spontaneous preterm birth[J]. Epidemiology,2009,20(5):707-713.
[26]Kasimanickam RK, Kasimanickam VR, Haldorson GJ, et al. Effect of tocopherol supplementation during last trimester of pregnancy on mRNA abundances of interleukins and angiogenesis in ovine placenta and uterus [J]. Reprod Biol Endocrinol, 2012,10:4.
[27]Kasimanickam RK, Kasimanickam VR. Effect of tocopherol supplementation on serum 8-epi-prostaglandin F2 alpha and adiponectin concentrations, and mRNA expression of PPARy and related genes in ovine placenta and uterus [J]. Theriogenology,2011,76(3):482-491.
[28]Rooke JA, Matheson S, Ison S, et al. The effect of late pregnancy supplementation of ewes with vitamin E on lamb vigour[J]. Animal,2009,3(11):1555-1561.
[29]Kelvin EA, Edwards S, Jedrychowski W, et al. Modulation of the effect of prenatal PAH exposure on PAH-DNA adducts in cord blood by plasma antioxidants[J]. Cancer Epidemiol Biomarkers Prev,2009,18(8):2262-2268.
[30]de Lira LQ, Ribeiro PP, Grilo EC, et al. Alpha-tocopherol level in serum and colostrum of breastfeeding women and association with maternal variables [J]. Rev Bras Ginecol Obstet,2012,34(8):362-368.
[31]Ambrogini P, Ciuffoli S, Lattanzi D, et al. Maternal dietary loads of a-tocopherol differentially influence fear conditioning and spatial learning in adult offspring [J]. Physiol Behav,2011,104(5):809-815.
[32]Fiore G, Capasso A. Effects of vitamin E and C on placental oxidative stress:an in vitro evidence for the potential therapeutic or prophylactic treatment of preeclampsia[J]. Med Chem,2008,4(6):526-530.
[33]Gohil JT, Patel PK, Gupta P. Evaluation of oxidative stress and antioxidant defence in subjects of preeclampsia[J]. J Obstet Gynaecol India,2011,61(6):638-640.
[34]Kolusari A, Kurdoglu M, Yildizhan R, et al. Catalase activity, serum trace element and heavy metal concentrations, and vitamin A, D and E levels in pre-eclampsia[J]. J Int Med Res,2008,36(6):1335-1341.
[35]Bowen RS, Moodley J, Dutton MF, et al. Oxidative stress in preeclampsia[J]. Acta Obstet Gynecol Scand,2001,80(8):719-725.
[36]Kontic-Vucinic O, Terzic M, Radunovic N. The role of antioxidant vitamins in hypertensive disorders of pregnancy[J]. J Perinat Med,2008,36(4):282-290.
[37]McCance DR, Holmes VA, Maresh MJ, et al. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT):a randomised placebo-controlled trial[J]. Lancet,2010,376(9737):259-266.
[38]Conde-Agudelo A, Romero R, Kusanovic JP, et al. Supplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes:a systematic review and metaanalysis[J]. Am J Obstet Gynecol,2011,204(6):503.
[39]Rossi AC, Mullin PM. Prevention of pre-eclampsia with low-dose aspirin or vitamins C and E in women at high or low risk:a systematic review with meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol,2011,158(1):9-16.
[40]Ben Hamida C, Doerflinger N, Belal S, et al. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome8q by homozygosity mapping[J]. Nature Genetics,1993,5(2):195-200.
[41]Packer L, Fuchs J. Vitamin E in Health and Disease[M]. New York:Marcel Dekker, 1993:815-849.
[42]Stumpf DA SR, Bettis D, Neville H, et al. Friedreich's disease:V. Variant form with vitamin E deficiency and normal fat absorption[J]. Neurology,1987,37(1):68-74.
[43]Belal S, Hentati F, Ben Hamida C, et al. Friedreich's ataxia-vitamin E responsive type. The chromosome 8 locus[J]. Clin Neurosci,1995,3:39-42.
[44]Dror DK, Allen LH. Vitamin E deficiency in developing countries [J]. Food Nutr Bull, 2011,32(2):124-143.
[45]Jishage K, Arita M, Igarashi K, et al. Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice[J]. J Biol Chem.2001,19,276(3):1669-1672.
[46]Brigelius-Flohe R, Kelly FJ, Salonen JT, et al. The European perspective on vitamin E:current knowledge and future research[J]. Am J Clin Nutr,2002,76(4):703-16.
[47]Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes[J]. Am J Clin Nutr,2005,81(4)-.736-745.
[48]Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease:a systematic review[J]. J Intern Med,2002,251(5):372-392.
[49]Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis:high-dosage vitamin E supplementation may increase all-cause mortality[J]. Ann Intern Med,2005, 142(1):37-46.
[50]Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer:a randomized controlled trial[J]. JAMA,2005, 293(11):1338-1347.
[51]Chappell LC, Seed PT, Kelly FJ, et al. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function[J]. Am J Obstet Gynecol,2002,187(3):777-784.
[52]Jishage K, Tachibe T, Ito T, et al. Vitamin E is essential for mouse placentation but not for embryonic development itself[J]. Biol Reprod,2005,73(5):983-987.
[2]Olcott HS, Emerson OH. Antioxidants and the autoxidantion of fats. Ⅸ. The antioxidant properties of the tocopherol[J]. J Am Chem Soc,1937,59:1008-1009.
[3]Brigelius-Flohe R, Kelly FJ, Salonen JT, et al. The European perspective on vitamin E:current knowledge and future research[J]. Am J Clin Nutr,2002,76(4):703-16.
[4]Kelly F, Meydani M, Packer L. Vitamin E and Health[J]. Annals of the New York Academy of Sciences,2004,1031:463.
[5]Evans HM, Burr GO. The Anti-Sterility Vitamine Fat Soluble E[J]. Proc Natl Acad SciUSA,1925,11(6):334-341.
[6]Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more[J]. Free Radic Biol Med,2007,43(1):4-15.
[7]Jishage K, Arita M, Igarashi K, et al. Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice[J]. J Biol Chem,2001,276(3):1669-1672.
[8]Kaempf-Rotzoll DE, Igarashi K, Aoki J, et al. Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus [J]. Biol Reprod,2002,67(2):599-604.
[9]Jishage K, Tachibe T, Ito T, et al. Vitamin E is essential for mouse placentation but not for embryonic development itself[J]. Biol Reprod,2005,73(5):983-987.
[10]Debier C. Vitamin E during pre- and postnatal periods[J]. Vitam Horm,2007, 76:357-373.
[11]Hacquebard M, Carpentier YA. Vitamin E:Absorption, plasma transport and cell uptake[J]. Curr Opin Clin Nutr Metab Care,2005,8(2):133-138.
[12]Kaliora AC, Dedoussis GV, Schmidt H. Dietary antioxidants in preventing atherogenesis[J]. Atherosclerosis,2006,187(1):1-17.
[13]Azzi A. Molecular mechanism of alpha-tocopherol action[J]. Free Radic Biol Med, 2007,43(1):16-21.
[14]Zingg JM, Meydani M, Azzi A. a-Tocopheryl phosphate--an activated form of vitamin E important for angiogenesis and vasculogenesis[J]? Biofactors,2012, 38(1):24-33.
[15]Molano A, Meydani SN. Vitamin E, signalosomes and gene expression in T cells[J]. Mol Aspects Med,2012,33(1):55-62.
[16]Rimbach G, Moehring J, Huebbe P, et al. Gene-regulatory activity of alpha-tocopherol[J]. Molecules,2010,15(3):1746-1761.
[17]Galli F, Azzi A. Present trends in vitamin E research[J]. Biofactors,2010, 36(1):33-42.
[18]Banerjee S, Chambers AE, Campbell S. Is vitamin E a safe prophylaxis for preeclampsia[J]? Am J Obstet Gynecol,2006,194(5):1228-1233.
[19]Shaw HM, Huang CJ. Liver alpha-tocopherol transfer protein and its mRNA are differentially altered by dietary vitamin E deficiency and protein insufficiency in rats[J]. J Nutr,1998,128(12):2348-2354.
[20]Mustacich DJ, Leonard SW, Devereaux MW, Sokol RJ, Traber MG. Alpha-tocopherol regulation of hepatic cytochrome P450s and ABC transporters in rats[J]. Free Radic Biol Med,2006,41:1069-1078.
[21]Li YF, Xu XB, Chen XH, et al. The nuclear factor-κB pathway is involved in matrix metalloproteinase-9 expression in RU486-induced endometrium breakdown in mice[J]. Hum Reprod,2012,27(7):2096-2106.
[22]Daikoku T, Matsumoto H, Gupta RA, et al. Expression of hypoxia-inducible factors in the peri-implantation mouse uterus is regulated in a cell-specific and ovarian steroid hormone-dependent manner. Evidence for differential function of HIFs during early pregnancy [J]. J Biol Chem,2003,278(9):7683-7691.
[23]Zhang B, Tanaka J, Yang L, et al. Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1[J].Neuroscience,2004,126(2):433-440.
[24]Xu JP, Yin YP, Zhou XQ. Effect of vitamin E on reproductive function in the mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Toxicol Ind Health,2008, 24(9):595-601.
[25]Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes[J]. Am J Clin Nutr,2005,81(4):736-745.
[26]Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease:a systematic review[J]. J Intern Med,2002,251(5):372-392.
[27]Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis:high-dosage vitamin E supplementation may increase all-cause mortality[J]. Ann Intern Med,2005, 142(1):37-46.
[28]Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer:a randomized controlled trial[J]. JAMA,2005, 293(11):1338-1347.
[29]Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention:systematic review and meta-analysis[J]. JAMA,2007,297(8):842-857.
[30]Chappell LC, Seed PT, Kelly FJ, et al. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function[J]. Am J Obstet Gynecol,2002,187(3):777-784.
[31]Ye X, Hama K, Contos JJ, et al. LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing[J]. Nature,2005,435(7038):104-108.
[32]Azzi A, Gysin R, Kempna P, et al. Vitamin E mediates cell signaling and regulation of gene expression[J]. Ann N Y Acad Sci,2004,1031:86-95.
[33]Ouahchi K, Arita M, Kayden H, et al. Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein[J]. Nat Genet,1995, 9(2):141-145.
[34]Copp RP, Wisniewski T, Hentati F, et al. Localization of alpha-tocopherol transfer protein in the brains of patients with ataxia with vitamin E deficiency and other oxidative stress related neurodegenerative disorders[J]. Brain Res,1999, 822(1-2):80-87.
[35]Gohil K, Godzdanker R, O'Roark E, et al. Alpha-tocopherol transfer protein deficiency in mice causes multi-organ deregulation of gene networks and behavioral deficits with age [J]. Ann N Y Acad Sci,2004,1031:109-126.
[36]Hosomi A, Goto K, Kondo H, et al. Localization of alpha-tocopherol transfer protein in rat brain[J]. Neurosci Lett,1998,256(3):159-162.
[37]Kaempf-Rotzoll DE, Horiguchi M, Hashiguchi K, et al. Human placental trophoblast cells express alpha-tocopherol transfer protein[J]. Placenta,2003,24(5):439-444.
[38]Tabanelli S, Tang B, Gurpide E. In vitro decidualization of human endometrial stromal cells[J]. J Steroid Biochem Mol Biol,1992,42(3-4):337-344.
[39]Telgmann R, Gellersen B. Marker genes of decidualization:activation of the decidual prolactin gene[J]. Hum Reprod Update,1998,4(5):472-479.
[40]Tseng L, Mazella J. Endometrial cell specific gene activation during implantation and early pregnancy[J]. Front Biosci,2002,7:d1566-1574.
[41]Chen GT, Getsios S, MacCalman CD. Cadherin-11 is a hormonally regulated cellular marker of decidualization in human endometrial stromal cells [J]. Mol Reprod Dev, 1999,52(2):158-165.
[42]Xu XB, He B, Wang JD. Menstrual-like changes in mice are provoked through the pharmacologic withdrawal of progesterone using mifepristone following induction of decidualization[J]. Hum Reprod,2007,22(12):3184-3191.
[43]Finn CA, Keen PM. The induction of deciduomata in the rat[J]. J Embryol Exp Morphol,1963,11:673-682.
[44]Hwang SY, Greenway AL, McMullen GL, et al. Detection of cells producing murine interferon-alpha using antipeptide antibodies [J]. Immunol Cell Biol,1994, 72(3):234-240.
[45]Traber MG, Arai H. Molecular mechanisms of vitamin E transport[J]. Annu Rev Nutr,1999,19:343-355.
[46]Robert BR, Janos Z, John WS, et al. Handbook of vitamins, third Edition (M). New York:Marcel Dekker,2001:170-171.
[47]Rotzoll DE, Scherling R, Etzl R, et al. Immunohistochemical localization of alpha-tocopherol transfer protein and lipoperoxidation products in human first-trimester and term placenta[J]. Eur J Obstet Gynecol Reprod Biol,2008, 140(2):183-191.
[48]Muller-Schmehl K, Beninde J, Finckh B, et al. Localization of alpha-tocopherol transfer protein in trophoblast, fetal capillaries' endothelium and amnion epithelium of human term placenta[J]. Free Radic Res,2004,38(4):413-420.
[49]Das P, Chowdhury M. Vitamin E-deficiency induced changes in ovary and uterus[J]. Mol Cell Biochem,1999,198(1-2):151-156.
[50]Hempstock J, Cindrova-Davies T, Jauniaux E, et al. Endometrial glands as a source of nutrients, growth factors and cytokines during the first trimester of human pregnancy:a morphological and immunohistochemical study[J]. Reprod Biol Endocrinol,2004,2:58.
[51]Arita M, Sato Y, Miyata A, et al. Human alpha-tocopherol transfer protein:cDNA cloning, expression and chromosomal localization [J]. Biochem J,1995,306(Pt 2):437-443.
[52]Sugino N. The role of oxygen radical-mediated signaling pathways in endometrial function[J]. Placenta,2007,28 Suppl A:S133-136.
[53]Riley JC, Behrman HR. Oxygen radicals and reactive oxygen species in reproduction[J]. Proc Soc Exp Biol Med,1991,198(3):781-791.
[54]Finn CA, Pope M. Vascular and cellular changes in the decidualized endometrium of the ovariectomized mouse following cessation of hormone treatment:a possible model for menstruation[J]. J Endocrinol,1984,100(3):295-300.
[55]Rogers PA. Structure and function of endometrial blood vessels[J]. Hum Reprod Update,1996,2(1):57-62.
[56]Rasweiler JJ 4th. Spontaneous decidual reactions and menstruation in the black mastiff bat,Molossus ater[J].Am J Anat,1991,191(1):1-22.
[57]Finn CA. Menstruation:a nonadaptive consequence of uterine evolution[J]. Q Rev Biol,1998,73(2):163-173.
[58]Ramathal CY, Bagchi IC, Taylor RN, et al. Endometrial decidualization:of mice and men[J]. Semin Reprod Med,2010,28(1):17-26.
[59]Mihm M, Gangooly S, Muttukrishna S. The normal menstrual cycle in women[J]. Anim Reprod Sci,2011,124(3-4):229-236.
[60]Terkel J. Neuroendocrine processes in the establishment of pregnancy and pseudopregnancy in rats[J]. Psychoneuroendocrinology,1988,13(1-2):5-28.
[61]Schlafke S, Welsh AO, Enders AC. Penetration of the basal lamina of the uterine luminal epithelium during implantation in the rat[J]. Anat Rec,1985,212(1):47-56.
[62]Evans HM. Spontaneous deciduomata in pseudopregnancy with low vitamin E[J]. Am J Physiol,1928,85 (1):149-153.
[63]Coppola JA, Ball JL, Brown HW. The incidence of spontaneous deciduomata in pseudopropregnant rats[J]. J Reprod Fertil,1966,12(2):389-390.
[64]Brosens JJ, Gellersen B. Something new about early pregnancy:decidual biosensoring and natural embryo selection[J]. Ultrasound Obstet Gynecol,2010, 36(1):1-5.
[65]Teklenburg G, Salker M, Heijnen C, et al. The molecular basis of recurrent pregnancy loss:impaired natural embryo selection[J]. Mol Hum Reprod,2010, 16(12):886-895.
[66]Shaikh AA. Estrone and estradiol levels in the ovarian venous blood from rats during the estrous cycle and pregnancy[J]. Biol Reprod,1971,5(3):297-307.
[67]Finn CA. Endocrine control of endometrial sensitivity during the induction of the decidual cell reaction in the mouse[J]. J Endocrinol,1966,36(3):239-248.
[68]Shelesnyak MC, Kraicer PF, Zeilmaker GH. Studies on the mechanism of decidualization[J]. I. Acta Endocrinol,1963,42 (2) 225-232.
[69]Hatamoto LK, Baptista Sobrinho CA, Nichi M, et al. Effects of dexamethasone treatment (to mimic stress) and Vitamin E oral supplementation on the spermiogram and on seminal plasma spontaneous lipid peroxidation and antioxidant enzyme activities in dogs[J]. Theriogenology,2006,66(6-7):1610-1614.
[70]Sugino N, Shimamura K, Takiguchi S, et al. Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy[J]. Hum Reprod,1996, 11(5):1073-1078.
[71]Andreyev AY, Kushnareva YE, Starkov AA. Mitochondrial metabolism of reactive oxygen species[J]. Biochemistry (Mosc),2005,70(2):200-214.
[1]Evans HM, Bishop KS. On the existence of a hitherto unrecognized dietary factor essential for reproduction[J]. Science,1922,56(1458):650-651.
[2]Ng MH, Choo YM, Ma AN, et al. Separation of vitamin E (tocopherol, tocotrienol, and tocomonoenol) in palm oil[J]. Lipids,2004,39(10):1031-1035.
[3]Yamamoto Y, Fujisawa A, Hara A, et al. An unusual vitamin E constituent (alpha-tocomonoenol) provides enhanced antioxidant protection in marine organisms adapted to cold-water environments [J]. Proc Natl Acad Sci U S A,2001, 98(23):13144-13148.
[4]Gianello R, Libinaki R, Azzi A, et al. Alpha-tocopheryl phosphate:a novel, natural form of vitamin E[J]. Free Radic Biol Med,2005,39(7):970-976.
[5]Munteanu A, Zingg JM, Ogru E, et al. Modulation of cell proliferation and gene expression by alpha-tocopheryl phosphates:relevance to atherosclerosis and inflammation[J]. Biochem Biophys Res Commun,2004,318(1):311-316.
[6]Negis Y, Zingg JM, Ogru E, et al. On the existence of cellular tocopheryl phosphate, its synthesis, degradation and cellular roles:a hypothesis[J]. IUBMB Life,2005, 57(1):23-25.
[7]Niki E. Role of vitamin E as lipid-soluble peroxyl radical scavenger:In vitro and in vivo evidence[J]. Free Radic Biol Med,2013, doi:10.1016/j.freeradbiomed. 2013.03.022.
[8]Wong RS, Radhakrishnan AK. Tocotrienol research:past into present[J]. Nutr Rev, 2012,70(9):483-490.
[9]Zingg JM, Meydani M, Azzi A. a-Tocopheryl phosphate--an activated form of vitamin E important for angiogenesis and vasculogenesis? [J]. Biofactors,2012, 38(1):24-33.
[10]Molano A, Meydani SN. Vitamin E, signalosomes and gene expression in T cells[J]. Mol Aspects Med,2012,33(1):55-62.
[11]Rimbach G, Moehring J, Huebbe P, et al. Gene-regulatory activity of alpha-tocopherol[J]. Molecules,2010,15(3):1746-1761.
[12]Galli F, Azzi A. Present trends in vitamin E research[J]. Biofactors,2010,36(1): 33-42.
[13]Lodge JK. Vitamin E bioavailability in humans[J]. J Plant Physiol,2005,162(7): 790-796.
[14]Schenker S, Yang Y, Perez A et al. Antioxidant transport by the human placenta[J]. Clin Nutr,1998,17(4):159-167.
[15]Jauniaux E, Cindrova-Davies T, Johns J, et al. Distribution and transfer pathways of antioxidant molecules inside the first trimester human gestational sac[J]. J Clin Endocrinol Metab,2004,89(3):1452-1458.
[16]Kaempf-Rotzoll DE, Horiguchi M, Hashiguchi K, et al. Human placental trophoblast cells express alpha-tocopherol transfer protein[J]. Placenta,2003,24(5):439-444.
[17]Muller-Schmehl K, Beninde J, Finckh B, et al. Localization of alpha-tocopherol transfer protein in trophoblast, fetal capillaries'endothelium and amnion epithelium of human term placenta[J]. Free Radic Res,2004,38(4):413-420
[18]Kaempf-Rotzoll, DE, Igarashi K, Aoki J, et al. Alpha-tocopherol transfer protein is specifically localized at the implantation site of pregnant mouse uterus[J]. Biol Reprod,2002,67(2):599-604.
[19]Browne RW, Bloom MS, Shelly WB, et al. Follicular fluid high density lipoprotein-associated micronutrient levels are associated with embryo fragmentation during IVF[J]. J Assist Reprod Genet,2009,26(11-12):557-560.
[20]Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases[J]. Hum Fertil (Camb),2009,12(4):198-203.
[21]Turner SW, Campbell D, Smith N, et al. Associations between fetal size, maternal {alpha}-tocopherol and childhood asthma[J]. Thorax,2010,65(5):391-397.
[22]McLernon PC, Wood LG, Murphy VE, et al. Circulating antioxidant profile of pregnant women with asthma[J]. Clin Nutr,2012,31(1):99-107.
[23]Vieira-Filho LD, Cabral EV, Santos FT, et al. Alpha-tocopherol prevents intrauterine undernutrition-induced oligonephronia in rats[J]. Pediatr Nephrol,2011, 26(11):2019-2029.
[24]Miller GW, Ulatowski L, Labut EM, et al. The a-tocopherol transfer protein is essential for vertebrate embryogenesis[J]. PLoS One,2012,7(10):e47402. doi: 10.1371
[25]Kramer MS, Kahn SR, Platt RW, et al. Antioxidant vitamins, long-chain fatty acids, and spontaneous preterm birth[J]. Epidemiology,2009,20(5):707-713.
[26]Kasimanickam RK, Kasimanickam VR, Haldorson GJ, et al. Effect of tocopherol supplementation during last trimester of pregnancy on mRNA abundances of interleukins and angiogenesis in ovine placenta and uterus [J]. Reprod Biol Endocrinol, 2012,10:4.
[27]Kasimanickam RK, Kasimanickam VR. Effect of tocopherol supplementation on serum 8-epi-prostaglandin F2 alpha and adiponectin concentrations, and mRNA expression of PPARy and related genes in ovine placenta and uterus [J]. Theriogenology,2011,76(3):482-491.
[28]Rooke JA, Matheson S, Ison S, et al. The effect of late pregnancy supplementation of ewes with vitamin E on lamb vigour[J]. Animal,2009,3(11):1555-1561.
[29]Kelvin EA, Edwards S, Jedrychowski W, et al. Modulation of the effect of prenatal PAH exposure on PAH-DNA adducts in cord blood by plasma antioxidants[J]. Cancer Epidemiol Biomarkers Prev,2009,18(8):2262-2268.
[30]de Lira LQ, Ribeiro PP, Grilo EC, et al. Alpha-tocopherol level in serum and colostrum of breastfeeding women and association with maternal variables [J]. Rev Bras Ginecol Obstet,2012,34(8):362-368.
[31]Ambrogini P, Ciuffoli S, Lattanzi D, et al. Maternal dietary loads of a-tocopherol differentially influence fear conditioning and spatial learning in adult offspring [J]. Physiol Behav,2011,104(5):809-815.
[32]Fiore G, Capasso A. Effects of vitamin E and C on placental oxidative stress:an in vitro evidence for the potential therapeutic or prophylactic treatment of preeclampsia[J]. Med Chem,2008,4(6):526-530.
[33]Gohil JT, Patel PK, Gupta P. Evaluation of oxidative stress and antioxidant defence in subjects of preeclampsia[J]. J Obstet Gynaecol India,2011,61(6):638-640.
[34]Kolusari A, Kurdoglu M, Yildizhan R, et al. Catalase activity, serum trace element and heavy metal concentrations, and vitamin A, D and E levels in pre-eclampsia[J]. J Int Med Res,2008,36(6):1335-1341.
[35]Bowen RS, Moodley J, Dutton MF, et al. Oxidative stress in preeclampsia[J]. Acta Obstet Gynecol Scand,2001,80(8):719-725.
[36]Kontic-Vucinic O, Terzic M, Radunovic N. The role of antioxidant vitamins in hypertensive disorders of pregnancy[J]. J Perinat Med,2008,36(4):282-290.
[37]McCance DR, Holmes VA, Maresh MJ, et al. Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT):a randomised placebo-controlled trial[J]. Lancet,2010,376(9737):259-266.
[38]Conde-Agudelo A, Romero R, Kusanovic JP, et al. Supplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes:a systematic review and metaanalysis[J]. Am J Obstet Gynecol,2011,204(6):503.
[39]Rossi AC, Mullin PM. Prevention of pre-eclampsia with low-dose aspirin or vitamins C and E in women at high or low risk:a systematic review with meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol,2011,158(1):9-16.
[40]Ben Hamida C, Doerflinger N, Belal S, et al. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome8q by homozygosity mapping[J]. Nature Genetics,1993,5(2):195-200.
[41]Packer L, Fuchs J. Vitamin E in Health and Disease[M]. New York:Marcel Dekker, 1993:815-849.
[42]Stumpf DA SR, Bettis D, Neville H, et al. Friedreich's disease:V. Variant form with vitamin E deficiency and normal fat absorption[J]. Neurology,1987,37(1):68-74.
[43]Belal S, Hentati F, Ben Hamida C, et al. Friedreich's ataxia-vitamin E responsive type. The chromosome 8 locus[J]. Clin Neurosci,1995,3:39-42.
[44]Dror DK, Allen LH. Vitamin E deficiency in developing countries [J]. Food Nutr Bull, 2011,32(2):124-143.
[45]Jishage K, Arita M, Igarashi K, et al. Alpha-tocopherol transfer protein is important for the normal development of placental labyrinthine trophoblasts in mice[J]. J Biol Chem.2001,19,276(3):1669-1672.
[46]Brigelius-Flohe R, Kelly FJ, Salonen JT, et al. The European perspective on vitamin E:current knowledge and future research[J]. Am J Clin Nutr,2002,76(4):703-16.
[47]Hathcock JN, Azzi A, Blumberg J, et al. Vitamins E and C are safe across a broad range of intakes[J]. Am J Clin Nutr,2005,81(4)-.736-745.
[48]Asplund K. Antioxidant vitamins in the prevention of cardiovascular disease:a systematic review[J]. J Intern Med,2002,251(5):372-392.
[49]Miller ER 3rd, Pastor-Barriuso R, Dalal D, et al. Meta-analysis:high-dosage vitamin E supplementation may increase all-cause mortality[J]. Ann Intern Med,2005, 142(1):37-46.
[50]Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer:a randomized controlled trial[J]. JAMA,2005, 293(11):1338-1347.
[51]Chappell LC, Seed PT, Kelly FJ, et al. Vitamin C and E supplementation in women at risk of preeclampsia is associated with changes in indices of oxidative stress and placental function[J]. Am J Obstet Gynecol,2002,187(3):777-784.
[52]Jishage K, Tachibe T, Ito T, et al. Vitamin E is essential for mouse placentation but not for embryonic development itself[J]. Biol Reprod,2005,73(5):983-987.