Contraception Targets in Mammalian Ovarian Development

Part of the Handbook of Experimental Pharmacology book series (HEP, volume 198)


In the human ovary, early in pre-natal life, oocytes are surrounded by pre-granulosa follicular cells to form primordial follicles. These primordial oocytes remain dormant, often for decades, until recruited into the growing pool throughout a woman’s adult reproductive years. Activation of follicle growth and subsequent development of growing oocytes in pre-antral follicles are major biological checkpoints that determine an individual females reproductive potential. In the past decade, great strides have been made in the elucidation of the molecular and cellular mechanisms underpinning maintenance of the quiescent primordial follicle pool and initiation and development of follicle growth. Gaining an in-depth knowledge of the intracellular signalling systems that control oocyte preservation and follicle activation has significant implications for improving female reproductive productivity and alleviating infertility. It also has application in domestic animal husbandry, feral animal population control and contraception in women.


Fertility control Granulosa cells Oocyte Primary follicle Primordial follicle 


  1. Aaltonen J et al (1999) Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. J Clin Endocrinol Metab 84:2744–2750PubMedCrossRefGoogle Scholar
  2. Adhikari D, Liu K (2009) Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev 30:438–464PubMedCrossRefGoogle Scholar
  3. Adhikari D et al (2009) Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles. Mol Hum Reprod 15:765–770PubMedCrossRefGoogle Scholar
  4. Adhikari D et al (2010) Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles. Hum Mol Genet 19:397–410PubMedCrossRefGoogle Scholar
  5. Andersen CY, Byskov AG (2006) Estradiol and regulation of anti-mullerian hormone, Inhibin-A, and Inhibin-B secretion: analysis of small antral and preovulatory human follicles’ fluid. J Clin Endocrinol Metab 91:4064–4069PubMedCrossRefGoogle Scholar
  6. Arraztoa JA et al (2005) Identification of genes expressed in primate primordial oocytes. Hum Reprod 20:476–483PubMedCrossRefGoogle Scholar
  7. Artac RA et al (2009) Neutralization of vascular endothelial growth factor antiangiogenic isoforms is more effective than treatment with proangiogenic isoforms in stimulating vascular development and follicle progression in the perinatal rat ovary. Biol Reprod 81:978–988PubMedCrossRefGoogle Scholar
  8. Behringer RR (1995) The mullerian inhibitor and mammalian sexual development. Philos Trans R Soc Lond B Biol Sci 350:285–288; discussion 289Google Scholar
  9. Brenkman AB, Burgering BM (2003) FoxO3a eggs on fertility and aging. Trends Mol Med 9:464–467PubMedCrossRefGoogle Scholar
  10. Britt KL et al (2004) Estrogen actions on follicle formation and early follicle development. Biol Reprod 71:1712–1723PubMedCrossRefGoogle Scholar
  11. Brown C et al (2009) Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKBalpha/Akt1. Biol Reprod 82(2):246–256PubMedCrossRefGoogle Scholar
  12. Carabatsos MJ et al (1998) Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol 204:373–384PubMedCrossRefGoogle Scholar
  13. Castrillon DH et al (2003) Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 301:215–218PubMedCrossRefGoogle Scholar
  14. Chen Y et al (2007) Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology 148:3580–3590PubMedCrossRefGoogle Scholar
  15. Chen Y et al (2009) Estrogen can signal through multiple pathways to regulate oocyte cyst breakdown and primordial follicle assembly in the neonatal mouse ovary. J Endocrinol 202:407–417PubMedCrossRefGoogle Scholar
  16. Choi Y, Rajkovic A (2006) Genetics of early mammalian folliculogenesis. Cell Mol Life Sci 63:579–590PubMedCrossRefGoogle Scholar
  17. Craig J et al (2007) Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death. Front Biosci 12:3628–3639PubMedCrossRefGoogle Scholar
  18. Da Silva-Buttkus P et al (2009) Inferring biological mechanisms from spatial analysis: prediction of a local inhibitor in the ovary. Proc Natl Acad Sci USA 106:456–461PubMedCrossRefGoogle Scholar
  19. David L et al (2009) Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 20:203–212PubMedCrossRefGoogle Scholar
  20. de Vet A et al (2002) Antimüllerian hormone serum levels: a putative marker for ovarian aging. Fertil Steril 77:357–362PubMedCrossRefGoogle Scholar
  21. Di Pasquale E et al (2004) Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 75:106–111PubMedCrossRefGoogle Scholar
  22. Di Pasquale E et al (2006) Identification of new variants of human BMP15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab 91:1976–1979PubMedCrossRefGoogle Scholar
  23. Dickinson RE et al (2010) Involvement of the SLIT/ROBO pathway in follicle development in the fetal ovary. Reproduction 139(2):395–407PubMedCrossRefGoogle Scholar
  24. Diclemente N et al (1994) Inhibitory effect of amh upon the expression of aromatase and lh receptors by cultured granulosa-cells of rat and porcine immature ovaries. Endocrine 2:553–558Google Scholar
  25. Dissen GA et al (2002) Neurotrophic control of ovarian development. Microsc Res Tech 59:509–515PubMedCrossRefGoogle Scholar
  26. Dissen GA et al (2009) Role of neurotrophic factors in early ovarian development. Semin Reprod Med 27:24–31PubMedCrossRefGoogle Scholar
  27. Dole G et al (2008) Glial derived neurotrophic factor promotes ovarian primordial follicle development and cell-cell interactions during folliculogenesis. Reproduction 135:671–682PubMedCrossRefGoogle Scholar
  28. Dong J et al (1996) Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531–535PubMedCrossRefGoogle Scholar
  29. Dono R et al (1998) Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient mice. EMBO J 17:4213–4225PubMedCrossRefGoogle Scholar
  30. Dube JL et al (1998) The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 12:1809–1817PubMedCrossRefGoogle Scholar
  31. Duffin K et al (2009) The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation. Mol Hum Reprod 15(12):771–777PubMedCrossRefGoogle Scholar
  32. Dumesic DA et al (2009) Intrafollicular antimullerian hormone levels predict follicle responsiveness to follicle-stimulating hormone (FSH) in normoandrogenic ovulatory women undergoing gonadotropin releasing-hormone analog/recombinant human FSH therapy for in vitro fertilization and embryo transfer. Fertil Steril 92:217–221PubMedCrossRefGoogle Scholar
  33. Durlinger ALL et al (1999) Control of primordial follicle recruitment by Anti-Mullerian hormone in the mouse ovary. Endocrinology 140:5789–5796PubMedCrossRefGoogle Scholar
  34. Durlinger ALL et al (2001) Anti-Mullerian hormone attenuates the effects of FSH on follicle development in the mouse ovary. Endocrinology 142:4891–4899PubMedCrossRefGoogle Scholar
  35. Durlinger AL et al (2002) Anti-Mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology 143:1076–1084PubMedCrossRefGoogle Scholar
  36. Edson MA et al (2009) The Mammalian ovary from genesis to revelation. Endocr Rev 30:624–712PubMedCrossRefGoogle Scholar
  37. Elvin JA et al (1999a) Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol 13:1035–1048PubMedCrossRefGoogle Scholar
  38. Elvin JA et al (1999b) Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Mol Endocrinol 13:1018–1034PubMedCrossRefGoogle Scholar
  39. Eppig JJ et al (2002) The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci USA 99:2890–2894PubMedCrossRefGoogle Scholar
  40. Furtado MB et al (2008) BMP/SMAD1 signaling sets a threshold for the left/right pathway in lateral plate mesoderm and limits availability of SMAD4. Genes Dev 22:3037–3049PubMedCrossRefGoogle Scholar
  41. Galloway SM et al (2000) Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet 25:279–283PubMedCrossRefGoogle Scholar
  42. Garor R et al (2009) Effects of basic fibroblast growth factor on in vitro development of human ovarian primordial follicles. Fertil Steril 91:1967–1975PubMedCrossRefGoogle Scholar
  43. Geissler EN et al (1981) Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse: a description of ten new W alleles. Genetics 97:337–361PubMedGoogle Scholar
  44. Gilchrist RB et al (2004) Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci 82–83:431–446PubMedCrossRefGoogle Scholar
  45. Gilchrist RB et al (2008) Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update 14:159–177PubMedCrossRefGoogle Scholar
  46. Gui LM, Joyce IM (2005) RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biol Reprod 72:195–199PubMedCrossRefGoogle Scholar
  47. Hanrahan JP et al (2004) Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod 70:900–909PubMedCrossRefGoogle Scholar
  48. Hansen KR et al (2008) A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod 23:699–708PubMedCrossRefGoogle Scholar
  49. Hayashi M et al (1999) Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology 140:1236–1244PubMedCrossRefGoogle Scholar
  50. Holt JE et al (2006) CXCR4/SDF1 interaction inhibits the primordial to primary follicle transition in the neonatal mouse ovary. Dev Biol 293(2):449–460PubMedCrossRefGoogle Scholar
  51. Hosaka T et al (2004) Disruption of forkhead transcription factor (FOXO) family members in mice reveals their functional diversification. Proc Natl Acad Sci USA 101:2975–2980PubMedCrossRefGoogle Scholar
  52. Hreinsson JG et al (2002) Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. J Clin Endocrinol Metab 87:316–321PubMedCrossRefGoogle Scholar
  53. Hutt KJ, Albertini DF (2006) Clinical applications and limitations of current ovarian stem cell research: a review. J Exp Clin Assist Reprod 3:6PubMedCrossRefGoogle Scholar
  54. Hutt KJ, Albertini DF (2007) An oocentric view of folliculogenesis and embryogenesis. Reprod Biomed Online 14:758–764PubMedCrossRefGoogle Scholar
  55. Hutt KJ et al (2006a) Kit ligand and c-Kit have diverse roles during mammalian oogenesis and folliculogenesis. Mol Hum Reprod 12(2):61–69PubMedCrossRefGoogle Scholar
  56. Hutt KJ et al (2006b) KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and murine ovarian follicle activation and oocyte growth. Biol Reprod 75:421–433PubMedCrossRefGoogle Scholar
  57. Jagarlamudi K et al (2009) Oocyte-specific deletion of Pten in mice reveals a stage-specific function of PTEN/PI3K signaling in oocytes in controlling follicular activation. PLoS One 4:e6186PubMedCrossRefGoogle Scholar
  58. Jin X et al (2005) Signal transduction of stem cell factor in promoting early follicle development. Mol Cell Endocrinol 229:3–10PubMedCrossRefGoogle Scholar
  59. John GB et al (2007) Specificity of the requirement for Foxo3 in primordial follicle activation. Reproduction 133:855–863PubMedCrossRefGoogle Scholar
  60. John GB et al (2008) Foxo3 is a PI3K-dependent molecular switch controlling the initiation of oocyte growth. Dev Biol 321:197–204PubMedCrossRefGoogle Scholar
  61. John GB et al (2009) Kit signaling via PI3K promotes ovarian follicle maturation but is dispensable for primordial follicle activation. Dev Biol 331:292–299PubMedCrossRefGoogle Scholar
  62. Juengel JL et al (2002) Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol Reprod 67:1777–1789PubMedCrossRefGoogle Scholar
  63. Juengel JL et al (2004) Physiology of GDF9 and BMP15 signalling molecules. Anim Reprod Sci 82–83:447–460PubMedCrossRefGoogle Scholar
  64. Junger MA et al (2003) The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2:20PubMedCrossRefGoogle Scholar
  65. Kaufmann E, Knochel W (1996) Five years on the wings of fork head. Mech Dev 57:3–20PubMedCrossRefGoogle Scholar
  66. Kevenaar ME et al (2007a) Anti-Mullerian hormone and anti-Mullerian hormone type II receptor polymorphisms are associated with follicular phase estradiol levels in normo-ovulatory women. Hum Reprod 22:1547–1554PubMedCrossRefGoogle Scholar
  67. Kevenaar ME et al (2007b) A polymorphism in the AMH type II receptor gene is associated with age at menopause in interaction with parity. Hum Reprod 22:2382–2388PubMedCrossRefGoogle Scholar
  68. Kezele P, Skinner MK (2003) Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: endocrine model of follicle assembly. Endocrinology 144:3329–3337PubMedCrossRefGoogle Scholar
  69. Kezele P et al (2002) Cell-cell interactions in primordial follicle assembly and development. Front Biosci 7:d1990–d1996PubMedCrossRefGoogle Scholar
  70. Kezele P et al (2005a) Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. Biol Reprod 73:967–973PubMedCrossRefGoogle Scholar
  71. Kezele PR et al (2005b) Alterations in the ovarian transcriptome during primordial follicle assembly and development. Biol Reprod 72:241–255PubMedCrossRefGoogle Scholar
  72. Kim H et al (2009a) Effects of diethylstilbestrol on ovarian follicle development in neonatal mice. Reprod Toxicol 27:55–62PubMedCrossRefGoogle Scholar
  73. Kim H et al (2009b) Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries. Biol Reprod 81:1002–1009PubMedCrossRefGoogle Scholar
  74. Knight PG, Glister C (2006) TGF-beta superfamily members and ovarian follicle development. Reproduction 132:191–206PubMedCrossRefGoogle Scholar
  75. Krysko DV et al (2008) Life and death of female gametes during oogenesis and folliculogenesis. Apoptosis 13:1065–1087PubMedCrossRefGoogle Scholar
  76. Lee WS et al (2001) Effect of bone morphogenetic protein-7 on folliculogenesis and ovulation in the rat. Biol Reprod 65:994–999PubMedCrossRefGoogle Scholar
  77. Lee WS et al (2004) Effects of bone morphogenetic protein-7 (BMP-7) on primordial follicular growth in the mouse ovary. Mol Reprod Dev 69:159–163PubMedCrossRefGoogle Scholar
  78. Lintern-Moore S et al (1974) Follicular development in the infant human ovary. J Reprod Fertil 39:53–64PubMedCrossRefGoogle Scholar
  79. Liu K et al (2006) Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: new roles for an old timer. Dev Biol 299:1–11PubMedCrossRefGoogle Scholar
  80. Liu L et al (2007a) Infertility caused by retardation of follicular development in mice with oocyte-specific expression of Foxo3a. Development 134:199–209PubMedCrossRefGoogle Scholar
  81. Liu L et al (2007b) Phosphorylation and inactivation of glycogen synthase kinase-3 by soluble kit ligand in mouse oocytes during early follicular development. J Mol Endocrinol 38:137–146PubMedCrossRefGoogle Scholar
  82. Lyet L et al (1996) Anti-mullerian hormone in relation to the growth and differentiation of the gubernacular primordia in mice. J Reprod Fertil 108:281–288PubMedCrossRefGoogle Scholar
  83. Macklon NS et al (2006) The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev 27:170–207PubMedCrossRefGoogle Scholar
  84. Maheshwari A, Fowler PA (2008) Primordial follicular assembly in humans – revisited. Zygote 16:285–296PubMedCrossRefGoogle Scholar
  85. Margulis S et al (2008) Bone morphogenetic protein 15 expression in human ovaries from fetuses, girls, and women. Fertil Steril 92:1666–1673PubMedCrossRefGoogle Scholar
  86. Matzuk MM et al (2002) Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science 296:2178–2180PubMedCrossRefGoogle Scholar
  87. McFee RM et al (2009) Inhibition of vascular endothelial growth factor receptor signal transduction blocks follicle progression but does not necessarily disrupt vascular development in perinatal rat ovaries. Biol Reprod 81:966–977PubMedCrossRefGoogle Scholar
  88. McGee EA, Hsueh AJ (2000) Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21:200–214PubMedCrossRefGoogle Scholar
  89. McGrath SA et al (1995) Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol 9:131–136PubMedCrossRefGoogle Scholar
  90. McLaughlin EA, McIver SC (2009) Awakening the oocyte: controlling primordial follicle development. Reproduction 137:1–11PubMedCrossRefGoogle Scholar
  91. McMahon HE et al (2008) Phosphorylation of bone morphogenetic protein-15 and growth and differentiation factor-9 plays a critical role in determining agonistic or antagonistic functions. Endocrinology 149:812–817PubMedCrossRefGoogle Scholar
  92. McNatty KP et al (2001) Genetic mutations influencing ovulation rate in sheep. Reprod Fertil Dev 13:549–555PubMedCrossRefGoogle Scholar
  93. McNatty KP et al (2005) Oocyte-expressed genes affecting ovulation rate. Mol Cell Endocrinol 234:57–66PubMedCrossRefGoogle Scholar
  94. McNatty KP et al (2007) Control of ovarian follicular development to the gonadotrophin-dependent phase: a 2006 perspective. Soc Reprod Fertil Suppl 64:55–68PubMedGoogle Scholar
  95. Mishina Y et al (1999) High specificity of Mullerian-inhibiting substance signaling in vivo. Endocrinology 140:2084–2088PubMedCrossRefGoogle Scholar
  96. Morikawa Y et al (2009) BMP signaling regulates sympathetic nervous system development through Smad4-dependent and -independent pathways. Development 136:3575–3584PubMedCrossRefGoogle Scholar
  97. Munsterberg A, Lovell-Badge R (1991) Expression of the mouse anti-mullerian hormone gene suggests a role in both male and female sexual differentiation. Development 113:613–624PubMedGoogle Scholar
  98. Nelson SM et al (2007) Serum anti-Mullerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles–implications for individualization of therapy. Hum Reprod 22:2414–2421PubMedCrossRefGoogle Scholar
  99. Nelson SM et al (2009) Anti-Mullerian hormone-based approach to controlled ovarian stimulation for assisted conception. Hum Reprod 24:867–875PubMedCrossRefGoogle Scholar
  100. Nilsson EE, Skinner MK (2002) Growth and differentiation factor-9 stimulates progression of early primary but not primordial rat ovarian follicle development. Biol Reprod 67:1018–1024PubMedCrossRefGoogle Scholar
  101. Nilsson EE, Skinner MK (2003) Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol Reprod 69:1265–1272PubMedCrossRefGoogle Scholar
  102. Nilsson EE, Skinner MK (2009) Progesterone regulation of primordial follicle assembly in bovine fetal ovaries. Mol Cell Endocrinol 313(1–2):9–16PubMedCrossRefGoogle Scholar
  103. Nilsson E et al (2001) Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol 175:123–130PubMedCrossRefGoogle Scholar
  104. Nilsson EE et al (2002) Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol 188:65–73PubMedCrossRefGoogle Scholar
  105. Nilsson EE et al (2006) Platelet-derived growth factor modulates the primordial to primary follicle transition. Reproduction 131:1007–1015PubMedCrossRefGoogle Scholar
  106. Nilsson E et al (2007) Actions of anti-Mullerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition. Reproduction 134:209–221PubMedCrossRefGoogle Scholar
  107. Nilsson E et al (2009) Neurotrophin NT3 promotes ovarian primordial to primary follicle transition. Reproduction 138:697–707PubMedCrossRefGoogle Scholar
  108. Orisaka M et al (2006) Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage. Mol Endocrinol 20:2456–2468PubMedCrossRefGoogle Scholar
  109. Orisaka M et al (2009) Growth differentiation factor 9 promotes rat preantral follicle growth by up-regulating follicular androgen biosynthesis. Endocrinology 150:2740–2748PubMedCrossRefGoogle Scholar
  110. Otsuka F et al (2001) Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. J Biol Chem 276:11387–11392PubMedCrossRefGoogle Scholar
  111. Paredes A et al (2004) TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. Dev Biol 267:430–449PubMedCrossRefGoogle Scholar
  112. Pedersen T (1969) Follicle growth in the immature mouse ovary. Acta Endocrinol 62:117–132PubMedGoogle Scholar
  113. Pedersen T (1970) Follicle kinetics in the ovary of the cyclic mouse. Acta Endocrinol 64:304–323PubMedGoogle Scholar
  114. Pedersen T, Peters H (1968) Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil 17:555–557PubMedCrossRefGoogle Scholar
  115. Pedersen T, Peters H (1971) Follicle growth and cell dynamics in the mouse ovary during pregnancy. Fertil Steril 22:42–52PubMedGoogle Scholar
  116. Pepling ME et al (2009) Differences in oocyte development and estradiol sensitivity among mouse strains. Reproduction 139(2):349–357PubMedCrossRefGoogle Scholar
  117. Picton H et al (1998) The molecular basis of oocyte growth and development. Mol Cell Endocrinol 145:27–37PubMedCrossRefGoogle Scholar
  118. Picton HM et al (2008) The in vitro growth and maturation of follicles. Reproduction 136:703–715PubMedCrossRefGoogle Scholar
  119. Rajareddy S et al (2007) p27kip1 (cyclin-dependent kinase inhibitor 1B) controls ovarian development by suppressing follicle endowment and activation and promoting follicle atresia in mice. Mol Endocrinol 21:2189–2202PubMedCrossRefGoogle Scholar
  120. Reddy P et al (2005) Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Dev Biol 281:160–170PubMedCrossRefGoogle Scholar
  121. Reddy P et al (2008) Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science 319:611–613PubMedCrossRefGoogle Scholar
  122. Reddy P et al (2009) PDK1 signaling in oocytes controls reproductive aging and lifespan by manipulating the survival of primordial follicles. Hum Mol Genet 18:2813–2824PubMedCrossRefGoogle Scholar
  123. Reynaud K, Driancourt MA (2000) Oocyte attrition. Mol Cell Endocrinol 163:101–108PubMedCrossRefGoogle Scholar
  124. Richards JS et al (2002) Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res 57:195–220PubMedCrossRefGoogle Scholar
  125. Rodrigues P et al (2008) Oogenesis: prospects and challenges for the future. J Cell Physiol 216:355–365PubMedCrossRefGoogle Scholar
  126. Rodrigues P et al (2009) Multiple mechanisms of germ cell loss in the perinatal mouse ovary. Reproduction 137:709–720PubMedCrossRefGoogle Scholar
  127. Romero C et al (2002) Nerve growth factor induces the expression of functional FSH receptors in newly formed follicles of the rat ovary. Endocrinology 143:1485–1494PubMedCrossRefGoogle Scholar
  128. Rowlands S (2009) New technologies in contraception. BJOG 116:230–239PubMedCrossRefGoogle Scholar
  129. Schmidt KL et al (2005) Anti-Mullerian hormone initiates growth of human primordial follicles in vitro. Mol Cell Endocrinol 234:87–93PubMedCrossRefGoogle Scholar
  130. Serafica MD et al (2005) Transcripts from a human primordial follicle cDNA library. Hum Reprod 20:2074–2091PubMedCrossRefGoogle Scholar
  131. Shimasaki S et al (2003) The role of bone morphogenetic proteins in ovarian function. Reprod Suppl 61:323–337PubMedGoogle Scholar
  132. Skinner MK (2005) Regulation of primordial follicle assembly and development. Hum Reprod Update 11:461–471PubMedCrossRefGoogle Scholar
  133. Solovyeva EV et al (2000) Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis. Biol Reprod 63:1214–1218PubMedCrossRefGoogle Scholar
  134. Spears N et al (2003) The role of neurotrophin receptors in female germ-cell survival in mouse and human. Development 130:5481–5491PubMedCrossRefGoogle Scholar
  135. Stewart CL et al (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359:76–79PubMedCrossRefGoogle Scholar
  136. Su YQ et al (2004) Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice: genetic evidence for an oocyte-granulosa cell regulatory loop. Dev Biol 276:64–73PubMedCrossRefGoogle Scholar
  137. Su YQ et al (2008) Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development 135:111–121PubMedCrossRefGoogle Scholar
  138. Su YQ et al (2009) Mouse oocyte control of granulosa cell development and function: paracrine regulation of cumulus cell metabolism. Semin Reprod Med 27:32–42PubMedCrossRefGoogle Scholar
  139. Sugiura K et al (2007) Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development 134:2593–2603Google Scholar
  140. Teixeira Filho FL et al (2002) Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome. J Clin Endocrinol Metab 87:1337–1344PubMedCrossRefGoogle Scholar
  141. Tingen C et al (2009) The primordial pool of follicles and nest breakdown in mammalian ovaries. Mol Hum Reprod 15(12):795–803PubMedCrossRefGoogle Scholar
  142. Trombly DJ et al (2009) Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin Reprod Med 27:14–23PubMedCrossRefGoogle Scholar
  143. Uda M et al (2004) Foxl2 disruption causes mouse ovarian failure by pervasive blockage of follicle development. Hum Mol Genet 13:1171–1181PubMedCrossRefGoogle Scholar
  144. van Rooij IAJ et al (2002) Serum anti-Mullerian hormone levels: a novel measure of ovarian reserve. Hum Reprod 17:3065–3071PubMedCrossRefGoogle Scholar
  145. Visser JA, Themmen APN (2005) Anti-Müllerian hormone and folliculogenesis. Mol Cell Endocrinol 234:81–86PubMedCrossRefGoogle Scholar
  146. Visser JA et al (2006) Anti-Mullerian hormone: a new marker for ovarian function. Reproduction 131:1–9PubMedCrossRefGoogle Scholar
  147. Vitt UA et al (2000) Growth differentiation factor-9 stimulates proliferation but suppresses the follicle-stimulating hormone-induced differentiation of cultured granulosa cells from small antral and preovulatory rat follicles. Biol Reprod 62:370–377PubMedCrossRefGoogle Scholar
  148. Vitt UA et al (2002) Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol Reprod 67:473PubMedCrossRefGoogle Scholar
  149. Wandji SA et al (1996) FSH and growth factors affect the growth and endocrine function in vitro of granulosa cells of bovine preantral follicles. Theriogenology 45:817–832PubMedCrossRefGoogle Scholar
  150. Wang N et al (2009) Comparative proteome profile of immature rat ovary during primordial follicle assembly and development. Proteomics 9:3425–3434PubMedCrossRefGoogle Scholar
  151. Weenen C et al (2004) Anti-Mullerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment. Mol Hum Reprod 10:77–83PubMedCrossRefGoogle Scholar
  152. Wu X et al (2004) Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice. Mol Endocrinol 18:1509–1519PubMedCrossRefGoogle Scholar
  153. Xiao YT et al (2007) Bone morphogenetic protein. Biochem Biophys Res Commun 362:550–553PubMedCrossRefGoogle Scholar
  154. Yamamoto N et al (2002) Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells. J Clin Endocrinol Metab 87:2849–2856PubMedCrossRefGoogle Scholar
  155. Yan C et al (2001) Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol 15:854–866PubMedCrossRefGoogle Scholar
  156. Yang MY, Fortune JE (2008) The capacity of primordial follicles in fetal bovine ovaries to initiate growth in vitro develops during mid-gestation and is associated with meiotic arrest of oocytes. Biol Reprod 78:1153–1161PubMedCrossRefGoogle Scholar
  157. Yang JL et al (2010) Testosterone induces redistribution of forkhead box-3a and down-regulation of growth and differentiation factor 9 messenger ribonucleic acid expression at early stage of mouse folliculogenesis. Endocrinology 151(2):774–782PubMedCrossRefGoogle Scholar
  158. Yoshino O et al (2006) A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Proc Natl Acad Sci USA 103:10678–10683Google Scholar
  159. Zheng P, Dean J (2007) Oocyte-specific genes affect folliculogenesis, fertilization, and early development. Semin Reprod Med 25:243–251PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Eileen A. McLaughlin
    • 1
    • 2
  • Alexander P. Sobinoff
    • 1
  1. 1.Reproductive Science Group, School of Environmental & Life SciencesUniversity of NewcastleCallaghanAustralia
  2. 2.ARC Centre of Excellence in Biotechnology & DevelopmentUniversity of NewcastleCallaghanAustralia

Personalised recommendations