哺乳动物卵泡生长发育相关分子通路研究进展

doi:10.16431/j.cnki.1671-7236.2015.05.034

摘要/Abstract

摘要： 生殖发育关系到一个物种的繁衍生息。哺乳动物的雌性生殖细胞,也就是卵母细胞,其生殖能力的获得需要同时经历两个过程:卵子发生和卵泡发育,而这两个相互依存的过程将为雌雄配子相互结合及新一代个体发育的起始奠定基础。随着分子生物学技术的发展,许多与卵泡发育相关的基因表达调控机制逐渐被揭示出来,新观点纷纷涌现。作者将对哺乳动物卵泡生长发育各阶段的主要分子通路研究进展进行综述,旨在为卵子干细胞的研究、治疗性克隆的发展、卵子减少不孕症等人类疾病的治疗和研究提供理论依据;此外,本综述还将对畜牧业中加快卵泡的发育进程、充分利用早期卵母细胞资源、缩短世代间隔、提高繁殖率等产生重要的指导意义。

关键词: 卵泡发育; 卵母细胞成熟; 基因表达调控; 分子通路

Abstract: Reproductive development is related to the survival and thrives of one species.The female mammalian germ cell, that is oocyte, will obtain their reproductive capacity through two processes:Oogenesis and follicle development.These two interdependent processes will provide the foundations for the combination of male and female gametes, and for the starting of a new generation of ontogeny.With the development of molecular biology techniques, many regulatory mechanisms of gene expressions, which associated with follicle development, is revealed gradually.New ideas have emerged.This present review will summarize the major molecular pathways, which occurred at different mammalian follicle development stages.And these summarizations will provide theoretical basis for the studies of germ stem cells, development of therapeutic cloning, and the treatment and research of human reproductive diseases.In addition, the paper will also show the guiding significance to the acceleration of development of animal husbandry, utilization of early oocytes resources, shortening of the generation interval and improvement of reproductive rate.

Key words: follicule development; oocyte maturation; regulation of gene expression; molecular pathways

中图分类号:

R714.1

宋嘉哲, 李文哲, 薛恺. 哺乳动物卵泡生长发育相关分子通路研究进展[J]. , 2015, 42(5): 1259-1267.

SONG Jia-zhe, LI Wen-zhe, XUE Kai. Research Progress on Molecular Pathways of Mammalian Ovary Follicle Development[J]. , 2015, 42(5): 1259-1267.

参考文献

[1] Dunlop C E, Anderson R A.The regulation and assessment of follicular growth[J].Scand J Clin Lab Invest Suppl, 2015, 244:13-17.
[2] Moor R M, Smith M W.Amino acid uptake into sheep oocytes[proceedings][J].J Physiol, 1978, 284:68P-69P.
[3] Baker T G.A quantitative and cytological study of germ cells in human ovaries[J].Proc R Soc Lond B Biol Sci, 1963, 158:417-433.
[4] Maheshwari A, Fowler P A.Primordial follicular assembly in humans——Revisited[J].Zygote, 2008, 16(4):285-296.
[5] McGee E A, Hsueh A J.Initial and cyclic recruitment of ovarian follicles[J].Endocr Rev, 2000, 21(2):200-214.
[6] Soyal S M, Amleh A, Dean J.FIG alpha, a germ cell-specific transcription factor required for ovarian follicle formation[J].Development, 2000, 127(21):4645-4654.
[7] Mottershead D G, Pulkki M M, Muggalla P, et al.Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells[J].Mol Cell Endocrinol, 2008, 283(1-2):58-67.
[8] Eppig J J.Oocyte control of ovarian follicular development and function in mammals[J].Reproduction, 2001, 122(6):829-838.
[9] Oktay K, Briggs D, Gosden R G.Ontogeny of follicle-stimulating hormone receptor gene expression in isolated human ovarian follicles[J].J Clin Endocrinol Metab, 1997, 82(11):3748-3751.
[10] Skinner M K.Regulation of primordial follicle assembly and development[J].Hum Reprod Update, 2005, 11(5):461-471.
[11] Durlinger A L, Gruijters M J, Kramer P, et al.Anti-mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary[J].Endocrinology, 2002, 143(3):1076-1084.
[12] Durlinger A L, Kramer P, Karels B, et al.Control of primordial follicle recruitment by anti-mullerian hormone in the mouse ovary[J].Endocrinology, 1999, 140(12):5789-5796.
[13] Schmidt D, Ovitt C E, Anlag K, et al.The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance[J].Development, 2004, 131(4):933-942.
[14] Bodensteiner K J, Clay C M, Moeller C L, et al.Molecular cloning of the ovine growth/differentiation factor-9 gene and expression of growth/differentiation factor-9 in ovine and bovine ovaries[J].Biol Reprod, 1999, 60(2):381-386.
[15] Eckery D C, Whale L J, Lawrence S B, et al.Expression of mRNA encoding growth differentiation factor 9 and bone morphogenetic protein 15 during follicular formation and growth in a marsupial, the brushtail possum (Trichosurus vulpecula)[J].Mol Cell Endocrinol, 2002, 192(1-2):115-126.
[16] Hayashi M, McGee E A, Min G, et al.Recombinant growth differentiation factor-9(GDF-9) enhances growth and differentiation of cultured early ovarian follicles[J].Endocrinology, 1999, 140(3):1236-1244.
[17] Sendai Y, Itoh T, Yamashita S, et al.Molecular cloning of a cDNA encoding a bovine growth differentiation factor-9(GDF-9) and expression of GDF-9 in bovine ovarian oocytes and in vitro-produced embryos[J].Cloning, 2001, 3(1):3-10.
[18] Vitt U A, McGee E A, Hayashi M, et al.In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats[J].Endocrinology, 2000, 141(10):3814-3820.
[19] Hirshfield A N.Relationship between the supply of primordial follicles and the onset of follicular growth in rats[J].Biol Reprod, 1994, 50(2):421-428.
[20] Hreinsson J G, Scott J E, Rasmussen C, et al.Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture[J].J Clin Endocrinol Metab, 2002, 87(1):316-321.
[21] Cheng L, Gearing D P, White L S, et al.Role of leukemia inhibitory factor and its receptor in mouse primordial germ cell growth[J].Development, 1994, 120(11):3145-3153.
[22] Nilsson E E, Kezele P, Skinner M K.Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries[J].Mol Cell Endocrinol, 2002, 188(1-2):65-73.
[23] Nilsson E E, Skinner M K.Growth and differentiation factor-9 stimulates progression of early primary but not primordial rat ovarian follicle development[J].Biol Reprod, 2002, 67(3):1018-1024.
[24] Nilsson E E, Skinner M K.Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition[J].Mol Cell Endocrinol, 2004, 214(1-2):19-25.
[25] Kezele P R, Nilsson E E, Skinner M K.Insulin but not insulin-like growth factor-1 promotes the primordial to primary follicle transition[J].Mol Cell Endocrinol, 2002, 192(1-2):37-43.
[26] Adhikari D, Zheng W, Shen Y, et al.Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles[J].Hum Mol Genet, 2010, 19(3):397-410.
[27] Castrillon D H, Miao L, Kollipara R, et al.Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a[J].Science, 2003, 301(5630):215-218.
[28] Rajareddy S, Reddy P, Du C, et al.p27kip1(cyclin-dependent kinase inhibitor 1B) controls ovarian development by suppressing follicle endowment and activation and promoting follicle atresia in mice[J].Mol Endocrinol, 2007, 21(9):2189-2202.
[29] Reddy P, Liu L, Adhikari D, et al.Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool[J].Science, 2008, 319(5863):611-613.
[30] John G B, Gallardo T D, Shirley L J, et al.Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth[J].Dev Biol, 2008, 321(1):197-204.
[31] Rajkovic A, Pangas S A, Ballow D, et al.NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression[J].Science, 2004, 305(5687):1157-1159.
[32] Knight P G, Glister C.TGF-beta superfamily members and ovarian follicle development[J].Reproduction, 2006, 132(2):191-206.
[33] Hulshof T, de Graaf C, Weststrate J A.Short-term effects of high-fat and low-fat/high-SPE croissants on appetite and energy intake at three deprivation periods[J].Physiol Behav, 1995, 57(2):377-383.
[34] Chegini N, Flanders K C.Presence of transforming growth factor-beta and their selective cellular localization in human ovarian tissue of various reproductive stages[J].Endocrinology, 1992, 130(3):1707-1715.
[35] Juengel J L, McNatty K P.The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development[J].Hum Reprod Update, 2005, 11(2):143-160.
[36] Roy S K, Kole A R.Ovarian transforming growth factor-beta(TGF-beta) receptors:In-vitro effects of follicle stimulating hormone, epidermal growth factor and TGF-beta on receptor expression in human preantral follicles[J].Mol Hum Reprod, 1998, 4(3):207-214.
[37] Adashi E Y, Resnick C E, Hernandez E R, et al.Ovarian transforming growth factor-beta(TGF beta):Cellular site(s), and mechanism(s) of action[J].Mol Cell Endocrinol, 1989, 61(2):247-256.
[38] Dodson W C, Schomberg D W.The effect of transforming growth factor-beta on follicle-stimulating hormone-induced differentiation of cultured rat granulosa cells[J].Endocrinology, 1987, 120(2):512-516.
[39] Saragueta P E, Lanuza G M, Baranao J L.Autocrine role of transforming growth factor beta1 on rat granulosa cell proliferation[J].Biol Reprod, 2002, 66(6):1862-1868.
[40] Dube J L, Wang P, Elvin J, et al.The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes[J].Mol Endocrinol, 1998, 12(2):1809-1817.
[41] Elvin J A, Yan C, Matzuk M M.Oocyte-expressed TGF-beta superfamily members in female fertility[J].Mol Cell Endocrinol, 2000, 159(1-2):1-5.
[42] Jaatinen R, Laitinen M P, Vuojolainen K, et al.Localization of growth differentiation factor-9 (GDF-9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF-9 and its novel homolog GDF-9B[J].Mol Cell Endocrinol, 1999, 156(1-2):189-193.
[43] Otsuka F, Yao Z, Lee T, et al.Bone morphogenetic protein-15.Identification of target cells and biological functions[J].J Biol Chem, 2000, 275(50):39523-39528.
[44] Galloway S M, McNatty K P, Cambridge L M, et al.Mutations in an oocyte-derived growth factor gene(BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner[J].Nat Genet, 2000, 25(3):279-283.
[45] Dong J, Albertini D F, Nishimori K, et al.Growth differentiation factor-9 is required during early ovarian folliculogenesis[J].Nature, 1996, 383(6600):531-535.
[46] Davis O K, Rosenwaks Z.Current status of in vitro fertilization and the new reproductive technologies[J].Curr Opin Obstet Gynecol, 1992, 4(3):354-358.
[47] Xiao S, Robertson D M, Findlay J K.Effects of activin and follicle-stimulating hormone(FSH)-suppressing protein/follistatin on FSH receptors and differentiation of cultured rat granulosa cells[J].Endocrinology, 1992, 131(3):1009-1016.
[48] Liu X, Andoh K, Yokota H, et al.Effects of growth hormone, activin, and follistatin on the development of preantral follicle from immature female mice[J].Endocrinology, 1998, 139(5):2342-2347.
[49] Mizunuma H, Liu X, Andoh K, et al.Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage[J].Endocrinology, 1999, 140(1):37-42.
[50] Oktem O, Oktay K.Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function[J].Cancer, 2007, 110(10):2222-2229.
[51] Findlay J K.An update on the roles of inhibin, activin, and follistatin as local regulators of folliculogenesis[J].Biol Reprod, 1993, 48(1):15-23.
[52] Guo Q, Kumar T R, Woodruff T, et al.Overexpression of mouse follistatin causes reproductive defects in transgenic mice[J].Mol Endocrinol, 1998, 12(1):96-106.
[53] Matzuk M M, Kumar T R, Bradley A.Different phenotypes for mice deficient in either activins or activin receptor type Ⅱ[J].Nature, 1995, 374(6520):356-360.
[54] Dias F C, Khan M I, Adams G P, et al.Granulosa cell function and oocyte competence:Super-follicles, super-moms and super-stimulation in cattle[J].Anim Reprod Sci, 2014, 149(1-2):80-89.
[55] Visser J A, Themmen A P.Anti-mullerian hormone and folliculogenesis[J].Mol Cell Endocrinol, 2005, 234(1-2):81-86.
[56] Yamoto M, Minami S, Nakano R, et al.Immunohistochemical localization of inhibin/activin subunits in human ovarian follicles during the menstrual cycle[J].J Clin Endocrinol Metab, 1992, 74(5):989-993.
[57] Hsueh A J, Dahl K D, Vaughan J, et al.Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis[J].Proc Natl Acad Sci USA, 1987, 84(14):5082-5086.
[58] Alak B M, Coskun S, Friedman C I, et al.Activin A stimulates meiotic maturation of human oocytes and modulates granulosa cell steroidogenesis in vitro[J].Fertil Steril, 1998, 70(6):1126-1130.
[59] Alak B M, Smith G D, Woodruff T K, et al.Enhancement of primate oocyte maturation and fertilization in vitro by inhibin A and activin A[J].Fertil Steril, 1996, 66(4):646-653.
[60] Sadatsuki M, Tsutsumi O, Yamada R, et al.Local regulatory effects of activin A and follistatin on meiotic maturation of rat oocytes[J].Biochem Biophys Res Commun, 1993, 196(1):388-395.
[61] Otsuka F, Moore R K, Iemura S, et al.Follistatin inhibits the function of the oocyte-derived factor BMP-15[J].Biochem Biophys Res Commun, 2001, 289(5):961-966.
[62] Erickson G F, Shimasaki S.The spatiotemporal expression pattern of the bone morphogenetic protein family in rat ovary cell types during the estrous cycle[J].Reprod Biol Endocrinol, 2003, 1:9.
[63] Shimasaki S, Moore R K, Otsuka F, et al.The bone morphogenetic protein system in mammalian reproduction[J].Endocr Rev, 2004, 25(1):72-101.
[64] Somers J P, DeLoia J A, Zeleznik A J.Adenovirus-directed expression of a nonphosphorylatable mutant of CREB (cAMP response element-binding protein) adversely affects the survival, but not the differentiation, of rat granulosa cells[J].Mol Endocrinol, 1999, 13(8):1364-1372.
[65] Somers J P, Benyo D F, Little-Ihrig L, et al.Luteinization in primates is accompanied by loss of a 43-kilodalton adenosine 3', 5'-monophosphate response element-binding protein isoform[J].Endocrinology, 1995, 136(11):4762-4768.
[66] Hummitzsch K, Anderson R A, Wilhelm D, et al.Stem cells, progenitor cells, and lineage decisions in the ovary[J].Endocr Rev, 2015, 36(1):65-91.
[67] Zou K, Yuan Z, Yang Z, et al.Production of offspring from a germline stem cell line derived from neonatal ovaries[J].Nat Cell Biol, 2009, 11(5):631-636.