Advertisement

Oogenesis pp 75-92 | Cite as

How the Oocyte Influences Follicular Cell Function and Why

  • Martin M. Matzuk
  • Qinglei LiEmail author
Chapter

Abstract

During ovarian follicular development, bidirectional communication between oocytes and their companion somatic cells is indispensable. The oocyte plays a leading role in regulating follicular cell development and function including growth and proliferation, apoptosis, differentiation, steroidogenesis, metabolism, and cumulus expansion. By modulating these critical functions, the oocyte orchestrates the rate of follicular development and creates a favorable microenvironment essential for its own development and destiny. A better understanding of the oocyte-somatic cell regulatory loop is essential for unraveling the myths surrounding oocyte developmental competence and may provide novel therapeutic strategies for female reproductive disorders resulting from defects in oocyte-follicle cell interactions.

Keywords

Oocyte Folliculogenesis Granulosa cells Transforming growth factor β Growth differentiation factor 9 (GDF9) Bone morphogenetic protein 15 

Notes

Acknowledgments

Studies in this area are supported by NIH grants HD33438 and HD32067 (to M. M. M.) and NIH grant HD073756 and Texas A&M new faculty start-up funds (to Q. L.).

References

  1. 1.
    Borum K. Oogenesis in the mouse. A study of the meiotic prophase. Exp Cell Res. 1961;24:495–507.PubMedGoogle Scholar
  2. 2.
    Hirshfield AN. Development of follicles in the mammalian ovary. Int Rev Cytol. 1991;124:43–101.PubMedGoogle Scholar
  3. 3.
    Maheshwari A, Fowler PA. Primordial follicular assembly in humans–revisited. Zygote. 2008;16:285–96.PubMedGoogle Scholar
  4. 4.
    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428:145–50.PubMedGoogle Scholar
  5. 5.
    Tilly JL, Niikura Y, Rueda BR. The current status of evidence for and against postnatal oogenesis in mammals: a case of ovarian optimism versus pessimism? Biol Reprod. 2009;80:2–12.PubMedGoogle Scholar
  6. 6.
    White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nat Med. 2012;18:413–21.PubMedGoogle Scholar
  7. 7.
    De Felici M. Germ stem cells in the mammalian adult ovary: considerations by a fan of the primordial germ cells. Mol Hum Reprod. 2010;16:632–6.PubMedGoogle Scholar
  8. 8.
    Adhikari D, Liu K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev. 2009;30:438–64.PubMedGoogle Scholar
  9. 9.
    Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil. 1968;17:555–7.PubMedGoogle Scholar
  10. 10.
    Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci. 2007;120:1330–40.PubMedGoogle Scholar
  11. 11.
    Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122:829–38.PubMedGoogle Scholar
  12. 12.
    Edson MA, Nagaraja AK, Matzuk MM. The mammalian ovary from genesis to revelation. Endocr Rev. 2009;30:624–712.PubMedGoogle Scholar
  13. 13.
    Kumar TR, Wang Y, Lu N, Matzuk MM. Follicle stimulating hormone is required for ovarian follicle maturation but not male fertility. Nat Genet. 1997;15:201–4.PubMedGoogle Scholar
  14. 14.
    Dierich A, Sairam MR, Monaco L, Fimia GM, Gansmuller A, LeMeur M, et al. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance. Proc Natl Acad Sci USA. 1998;95:13612–7.PubMedGoogle Scholar
  15. 15.
    Ma X, Dong Y, Matzuk MM, Kumar TR. Targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proc Natl Acad Sci USA. 2004;101:17294–9.PubMedGoogle Scholar
  16. 16.
    Park J-Y, Su Y-Q, Ariga M, Law E, Jin SLC, Conti M. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science. 2004;303:682–4.PubMedGoogle Scholar
  17. 17.
    Fan HY, Liu ZL, Shimada M, Sterneck E, Johnson PF, Hedrick SM, et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science. 2009;324:938–41.PubMedGoogle Scholar
  18. 18.
    Li Q, McKenzie LJ, Matzuk MM. Revisiting oocyte-somatic cell interactions: in search of novel intrafollicular predictors and regulators of oocyte developmental competence. Mol Hum Reprod. 2008;14:673–8.PubMedGoogle Scholar
  19. 19.
    Eppig JJ, Chesnel F, Hirao Y, O’Brien MJ, Pendola FL, Watanabe S, et al. Oocyte control of granulosa cell development: how and why. Hum Reprod. 1997;12:127–32.PubMedGoogle Scholar
  20. 20.
    Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update. 2008;14:159–77.PubMedGoogle Scholar
  21. 21.
    Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002;296:2178–80.PubMedGoogle Scholar
  22. 22.
    Hayashi M, McGee EA, Min G, Klein C, Rose UM, van Duin M, et al. Recombinant growth differentiation factor-9 (GDF-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology. 1999;140:1236–44.PubMedGoogle Scholar
  23. 23.
    Gilchrist RB, Ritter LJ, Myllymaa S, Kaivo-Oja N, Dragovic RA, Hickey TE, et al. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci. 2006;119:3811–21.PubMedGoogle Scholar
  24. 24.
    Hussein TS, Froiland DA, Amato F, Thompson JG, Gilchrist RB. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci. 2005;118:5257–68.PubMedGoogle Scholar
  25. 25.
    Eppig JJ, Wigglesworth K, Pendola F, Hirao Y. Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol Reprod. 1997;56:976–84.PubMedGoogle Scholar
  26. 26.
    Vitt UA, Hayashi M, Klein C, Hsueh AJW. 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. 2000;62:370–7.PubMedGoogle Scholar
  27. 27.
    Sugiura K, Su Y-Q, Diaz FJ, Pangas SA, Sharma S, Wigglesworth K, et al. Oocyte-derived BMP15 and FGFs cooperate to promote glycolysis in cumulus cells. Development. 2007;134:2593–603.PubMedGoogle Scholar
  28. 28.
    Su YQ, Sugiura K, Wigglesworth K, O’Brien MJ, Affourtit JP, Pangas SA, et al. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells. Development. 2008;135:111–21.PubMedGoogle Scholar
  29. 29.
    Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci USA. 2002;99:2890–4.PubMedGoogle Scholar
  30. 30.
    Gilchrist RB. Recent insights into oocyte-follicle cell interactions provide opportunities for the development of new approaches to in vitro maturation. Reprod Fertil Dev. 2011;23:23–31.PubMedGoogle Scholar
  31. 31.
    Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996;383:531–5.PubMedGoogle Scholar
  32. 32.
    Galloway SM, McNatty KP, Cambridge LM, Laitinen MPE, Juengel JL, Jokiranta TS, et al. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet. 2000;25:279–83.PubMedGoogle Scholar
  33. 33.
    Tomic D, Miller KP, Kenny HA, Woodruff TK, Hoyer P, Flaws JA. Ovarian follicle development requires Smad3. Mol Endocrinol. 2004;18:2224–40.PubMedGoogle Scholar
  34. 34.
    Hashimoto O, Moore RK, Shimasaki S. Posttranslational processing of mouse and human BMP-15: potential implication in the determination of ovulation quota. Proc Natl Acad Sci USA. 2005;102:5426–31.PubMedGoogle Scholar
  35. 35.
    Juengel JL, McNatty KP. The role of proteins of the transforming growth factor-beta superfamily in the intraovarian regulation of follicular development. Hum Reprod Update. 2005;11:144–61.Google Scholar
  36. 36.
    Dragovic RA, Ritter LJ, Schulz SJ, Amato F, Thompson JG, Armstrong DT, et al. Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansion. Biol Reprod. 2007;76:848–57.PubMedGoogle Scholar
  37. 37.
    Lee KY, Jeong JW, Wang J, Ma L, Martin JF, Tsai SY, et al. Bmp2 is critical for the murine uterine decidual response. Mol Cell Biol. 2007;27:5468–78.PubMedGoogle Scholar
  38. 38.
    Li Q, Pangas SA, Jorgez CJ, Graff JM, Weinstein M, Matzuk MM. Redundant roles of SMAD2 and SMAD3 in ovarian granulosa cells in vivo. Mol Cell Biol. 2008;28:7001–11.PubMedGoogle Scholar
  39. 39.
    Gong X, McGee EA. Smad3 is required for normal follicular follicle-stimulating hormone responsiveness in the mouse. Biol Reprod. 2009;81:730–8.PubMedGoogle Scholar
  40. 40.
    Li Q, Agno JE, Edson MA, Nagaraja AK, Nagashima T, Matzuk MM. Transforming growth factor β receptor type 1 is essential for female reproductive tract integrity and function. PLoS Genet. 2011;7:e1002320.PubMedGoogle Scholar
  41. 41.
    Myers M, Tripurani SK, Middlebrook B, Economides AN, Canalis E, Pangas SA. Loss of gremlin delays primordial follicle assembly but does not affect female fertility in mice. Biol Reprod. 2011;85:1175–82.PubMedGoogle Scholar
  42. 42.
    Li Q, Graff JM, O’Connor AE, Loveland KL, Matzuk MM. SMAD3 regulates gonadal tumorigenesis. Mol Endocrinol. 2007;21:2472–86.PubMedGoogle Scholar
  43. 43.
    Pangas SA, Li X, Umans L, Zwijsen A, Huylebroeck D, Gutierrez C, et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol. 2008;28:248–57.PubMedGoogle Scholar
  44. 44.
    Matzuk MM, Finegold MJ, Su JG, Hsueh AJ, Bradley A. Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature. 1992;360:313–9.PubMedGoogle Scholar
  45. 45.
    Edson MA, Nalam RL, Clementi C, Franco HL, Demayo FJ, Lyons KM, et al. Granulosa cell-­expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Mol Endocrinol. 2010;24:1251–66.PubMedGoogle Scholar
  46. 46.
    Middlebrook BS, Eldin K, Li X, Shivasankaran S, Pangas SA. Smad1-Smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. Endocrinology. 2009;150:5208–17.PubMedGoogle Scholar
  47. 47.
    Massague J. Receptors for the TGF-beta family. Cell. 1992;69:1067–70.PubMedGoogle Scholar
  48. 48.
    Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753–91.PubMedGoogle Scholar
  49. 49.
    Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-β superfamily. Endocr Rev. 2002;23:787–823.PubMedGoogle Scholar
  50. 50.
    Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol. 2000;1:169–78.PubMedGoogle Scholar
  51. 51.
    Moustakas A, Heldin CH. Non-Smad TGF-beta signals. J Cell Sci. 2005;118:3573–84.PubMedGoogle Scholar
  52. 52.
    Zhang YE. Non-Smad pathways in TGF-beta signaling. Cell Res. 2009;19:128–39.PubMedGoogle Scholar
  53. 53.
    Attisano L, Wrana JL. Signal transduction by the TGF-beta superfamily. Science. 2002;296:1646–7.PubMedGoogle Scholar
  54. 54.
    Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature. 2003;425:577–84.PubMedGoogle Scholar
  55. 55.
    Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai). 2009;41:263–72.Google Scholar
  56. 56.
    Yan XH, Chen YG. Smad7: not only a regulator, but also a cross-talk mediator of TGF-beta signalling. Biochem J. 2011;434:1–10.PubMedGoogle Scholar
  57. 57.
    Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol. 2001;15:854–66.PubMedGoogle Scholar
  58. 58.
    McNatty KP, Juengel JL, Wilson T, Galloway SM, Davis GH. Genetic mutations influencing ovulation rate in sheep. Reprod Fertil Dev. 2001;13:549–55.PubMedGoogle Scholar
  59. 59.
    McNatty KP, Hudson NL, Whiting L, Reader KL, Lun S, Western A, et al. The effects of immunizing sheep with different BMP15 or GDF9 peptide sequences on ovarian follicular activity and ovulation rate. Biol Reprod. 2007;76:552–60.PubMedGoogle Scholar
  60. 60.
    Juengel JL, Hudson NL, Berg M, Hamel K, Smith P, Lawrence SB, et al. Effects of active immunization against growth differentiation factor 9 and/or bone morphogenetic protein 15 on ovarian function in cattle. Reproduction. 2009;138:107–14.PubMedGoogle Scholar
  61. 61.
    Juengel JL, Quirke LD, Lun S, Heath DA, Johnstone PD, McNatty KP. Effects of immunizing ewes against bone morphogenetic protein 15 on their responses to exogenous gonadotrophins to induce multiple ovulations. Reproduction. 2011;142:565–72.PubMedGoogle Scholar
  62. 62.
    McIntosh CJ, Lawrence S, Smith P, Juengel JL, McNatty KP. Active immunization against the proregions of GDF9 or BMP15 alters ovulation rate and litter size in mice. Reproduction. 2012;143:195–201.PubMedGoogle Scholar
  63. 63.
    Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol. 1999;13:1035–48.PubMedGoogle Scholar
  64. 64.
    Vitt UA, McGee EA, Hayashi M, Hsueh AJW. In vivo treatment with GDF-9 stimulates primordial and primary follicle progression and theca cell marker CYP17 in ovaries of immature rats. Endocrinology. 2000;141:3814–20.PubMedGoogle Scholar
  65. 65.
    Otsuka F, Yao Z, Lee T-H, Yamamoto S, Erickson GF, Shimasaki S. Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem. 2000;275:39523–8.PubMedGoogle Scholar
  66. 66.
    Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJW, Hovatta O. Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. J Clin Endocrinol Metab. 2002;87:316–21.PubMedGoogle Scholar
  67. 67.
    Otsuka F, Yamamoto S, Erickson GF, Shimasaki S. Bone morphogenetic protein-15 inhibits follicle-­stimulating hormone (FSH) action by suppressing FSH receptor expression. J Biol Chem. 2001;276:11387–92.PubMedGoogle Scholar
  68. 68.
    Otsuka F, Shimasaki S. A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. Proc Natl Acad Sci USA. 2002;99:8060–5.PubMedGoogle Scholar
  69. 69.
    Shimasaki S, Moore RK, Otsuka F, Erickson GF. The bone morphogenetic protein system in mammalian reproduction. Endocr Rev. 2004;25:72–101.PubMedGoogle Scholar
  70. 70.
    McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function. Reproduction. 2005;129:473–80.PubMedGoogle Scholar
  71. 71.
    Yoshino O, McMahon HE, Sharma S, Shimasaki S. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Proc Natl Acad Sci USA. 2006;103:10678–83.PubMedGoogle Scholar
  72. 72.
    Edwards SJ, Reader KL, Lun S, Western A, Lawrence S, McNatty KP, et al. The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II. Endocrinology. 2008;149:1026–30.PubMedGoogle Scholar
  73. 73.
    McGrath SA, Esquela AF, Lee SJ. Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol. 1995;9:131–6.PubMedGoogle Scholar
  74. 74.
    Aaltonen J, Laitinen MP, Vuojolainen K, Jaatinen R, Horelli-Kuitunen N, Seppa L, et al. Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculogenesis. J Clin Endocrinol Metab. 1999;84:2744–50.PubMedGoogle Scholar
  75. 75.
    Elvin JA, Yan C, Wang P, Nishimori K, Matzuk MM. Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Mol Endocrinol. 1999;13:1018–34.PubMedGoogle Scholar
  76. 76.
    Joyce IM, Clark AT, Pendola FL, Eppig JJ. Comparison of recombinant growth differentiation factor-9 and oocyte regulation of KIT ligand messenger ribonucleic acid expression in mouse ovarian follicles. Biol Reprod. 2000;63:1669–75.PubMedGoogle Scholar
  77. 77.
    Packer AI, Hsu YC, Besmer P, Bachvarova RF. The ligand of the c-kit receptor promotes oocyte growth. Dev Biol. 1994;161:194–205.PubMedGoogle Scholar
  78. 78.
    Thomas FH, Ismail RS, Jiang JY, Vanderhyden BC. Kit ligand 2 promotes murine oocyte growth in vitro. Biol Reprod. 2008;78:167–75.PubMedGoogle Scholar
  79. 79.
    Orisaka M, Orisaka S, Jiang JY, Craig J, Wang YF, Kotsuji F, et al. Growth differentiation factor 9 is antiapoptotic during follicular development from preantral to early antral stage. Mol Endocrinol. 2006;20:2456–68.PubMedGoogle Scholar
  80. 80.
    McMahon HE, Hashimoto O, Mellon PL, Shimasaki S. Oocyte-specific overexpression of mouse bone morphogenetic protein-15 leads to accelerated folliculogenesis and an early onset of acyclicity in transgenic mice. Endocrinology. 2008;149:2807–15.PubMedGoogle Scholar
  81. 81.
    Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, et al. 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. 2004;70:900–9.PubMedGoogle Scholar
  82. 82.
    Montgomery GW, Zhao ZZ, Marsh AJ, Mayne R, Treloar SA, James M, et al. A deletion mutation in GDF9 in sisters with spontaneous DZ twins. Twin Res. 2004;7:548–55.PubMedGoogle Scholar
  83. 83.
    Di Pasquale E, Beck-Peccoz P, Persani L. Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet. 2004;75:106–11.PubMedGoogle Scholar
  84. 84.
    Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, Gupta N, et al. Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet. 2006;119:408–15.PubMedGoogle Scholar
  85. 85.
    Liu J, Wang B, Wei Z, Zhou P, Zu Y, Zhou S, et al. Mutational analysis of human bone morphogenetic protein 15 in Chinese women with polycystic ovary syndrome. Metabolism. 2011;60:1511–4.PubMedGoogle Scholar
  86. 86.
    Wei LN, Liang XY, Fang C, Zhang MF. Abnormal expression of growth differentiation factor 9 and bone morphogenetic protein 15 in stimulated oocytes during maturation from women with polycystic ovary syndrome. Fertil Steril. 2011;96:464–8.PubMedGoogle Scholar
  87. 87.
    Hanevik HI, Hilmarsen HT, Skjelbred CF, Tanbo T, Kahn JA. A single nucleotide polymorphism in BMP15 is associated with high response to ovarian stimulation. Reprod Biomed Online. 2011;23:97–104.PubMedGoogle Scholar
  88. 88.
    Su YQ, Wu X, O’Brien MJ, Pendola FL, Denegre JN, Matzuk MM, et al. 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. 2004;276:64–73.PubMedGoogle Scholar
  89. 89.
    McNatty KP, Juengel JL, Reader KL, Lun S, Myllymaa S, Lawrence SB, et al. Bone morphogenetic protein 15 and growth differentiation factor 9 co-operate to regulate granulosa cell function in ruminants. Reproduction. 2005;129:481–7.PubMedGoogle Scholar
  90. 90.
    Reader KL, Heath DA, Lun S, McIntosh CJ, Western AH, Littlejohn RP, et al. Signalling pathways involved in the cooperative effects of ovine and murine GDF9+BMP15-stimulated thymidine uptake by rat granulosa cells. Reproduction. 2011;142:123–31.PubMedGoogle Scholar
  91. 91.
    Mottershead DG, Ritter LJ, Gilchrist RB. Signalling pathways mediating specific synergistic interactions between GDF9 and BMP15. Mol Hum Reprod. 2012;18:121–8.PubMedGoogle Scholar
  92. 92.
    Palmer JS, Zhao ZZ, Hoekstra C, Hayward NK, Webb PM, Whiteman DC, et al. Novel variants in growth differentiation factor 9 in mothers of dizygotic twins. J Clin Endocrinol Metab. 2006;91:4713–6.PubMedGoogle Scholar
  93. 93.
    Zhao H, Qin Y, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A. Analyses of GDF9 mutation in 100 Chinese women with premature ovarian failure. Fertil Steril. 2007;88:1474–6.PubMedGoogle Scholar
  94. 94.
    Inagaki K, Shimasaki S. Impaired production of BMP-15 and GDF-9 mature proteins derived from proproteins with mutations in the proregion. Mol Cell Endocrinol. 2010;328:1–7.PubMedGoogle Scholar
  95. 95.
    Shimasaki S, Zachow RJ, Li DM, Kim H, Iemura S, Ueno N, et al. A functional bone morphogenetic protein system in the ovary. Proc Natl Acad Sci USA. 1999;96:7282–7.PubMedGoogle Scholar
  96. 96.
    Findlay JK, Drummond AE, Britt KL, Dyson M, Wreford NG, Robertson DM, et al. The roles of activins, inhibins and estrogen in early committed follicles. Mol Cell Endocrinol. 2000;163:81–7.PubMedGoogle Scholar
  97. 97.
    Knight PG. Roles of inhibins, activins, and follistatin in the female reproductive system. Front Neuroendocrinol. 1996;17:476–509.PubMedGoogle Scholar
  98. 98.
    Pangas SA, Jorgez CJ, Tran M, Agno J, Li X, Brown CW, et al. Intraovarian activins are required for female fertility. Mol Endocrinol. 2007;21:2458–71.PubMedGoogle Scholar
  99. 99.
    Pangas SA. Growth factors in ovarian development. Semin Reprod Med. 2007;25:225–34.PubMedGoogle Scholar
  100. 100.
    Sirotkin AV. Growth factors controlling ovarian functions. J Cell Physiol. 2011;226:2222–5.PubMedGoogle Scholar
  101. 101.
    Wijgerde M, Ooms M, Hoogerbrugge JW, Grootegoed JA. Hedgehog signaling in mouse ovary: Indian hedgehog and desert hedgehog from granulosa cells induce target gene expression in developing theca cells. Endocrinology. 2005;146:3558–66.PubMedGoogle Scholar
  102. 102.
    Russell MC, Cowan RG, Harman RM, Walker AL, Quirk SM. The hedgehog signaling pathway in the mouse ovary. Biol Reprod. 2007;77:226–36.PubMedGoogle Scholar
  103. 103.
    Zhang CP, Yang JL, Zhang J, Li L, Huang L, Ji SY, et al. Notch signaling is involved in ovarian follicle development by regulating granulosa cell proliferation. Endocrinology. 2011;152:2437–47.PubMedGoogle Scholar
  104. 104.
    Binelli M, Murphy BD. Coordinated regulation of follicle development by germ and somatic cells. Reprod Fertil Dev. 2010;22:1–12.PubMedGoogle Scholar
  105. 105.
    Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci. 2004;82–83:431–46.PubMedGoogle Scholar
  106. 106.
    Vanderhyden BC, Telfer EE, Eppig JJ. Mouse oocytes promote proliferation of granulosa-cells from preantral and antral follicles in vitro. Biol Reprod. 1992;46:1196–204.PubMedGoogle Scholar
  107. 107.
    Gilchrist RB, Ritter LJ, Armstrong DT. Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation. Dev Biol. 2001;240:289–98.PubMedGoogle Scholar
  108. 108.
    Gilchrist RB, Morrissey MP, Ritter LJ, Armstrong DT. Comparison of oocyte factors and transforming growth factor-beta in the regulation of DNA synthesis in bovine granulosa cells. Mol Cell Endocrinol. 2003;201:87–95.PubMedGoogle Scholar
  109. 109.
    Vitt UA, Mazerbourg S, Klein C, Hsueh AJW. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol Reprod. 2002;67:473–80.PubMedGoogle Scholar
  110. 110.
    Mazerbourg S, Klein C, Roh J, Kaivo-Oja N, Mottershead DG, Korchynskyi O, et al. Growth differentiation factor-9 signaling is mediated by the type I receptor, activin receptor-like kinase 5. Mol Endocrinol. 2004;18:653–65.PubMedGoogle Scholar
  111. 111.
    Kaivo-Oja N, Bondestam J, Kamarainen M, Koskimies J, Vitt U, Cranfield M, et al. Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells. J Clin Endocrinol Metab. 2003;88:755–62.PubMedGoogle Scholar
  112. 112.
    Kaivo-Oja N, Mottershead DG, Mazerbourg S, Myllymaa S, Duprat S, Gilchrist RB, et al. Adenoviral gene transfer allows Smad-responsive gene promoter analyses and delineation of type I receptor usage of transforming growth factor-beta family ligands in cultured human granulosa luteal cells. J Clin Endocrinol Metab. 2005;90:271–8.PubMedGoogle Scholar
  113. 113.
    Sasseville M, Ritter LJ, Nguyen TM, Liu F, Mottershead DG, Russell DL, et al. Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells. J Cell Sci. 2010;123:3166–76.PubMedGoogle Scholar
  114. 114.
    Moore RK, Otsuka F, Shimasaki S. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem. 2003;278:304–10.PubMedGoogle Scholar
  115. 115.
    Kaipia A, Hsueh AJW. Regulation of ovarian follicle atresia. Annu Rev Physiol. 1997;59:349–63.PubMedGoogle Scholar
  116. 116.
    Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update. 2005;11:162–77.PubMedGoogle Scholar
  117. 117.
    Jin X, Xiao LJ, Zhang XS, Liu YX. Apoptosis in ovary. Front Biosci. 2011;3:680–97.Google Scholar
  118. 118.
    Stocco C, Telleria C, Gibori G. The molecular control of corpus luteum formation, function, and regression. Endocr Rev. 2007;28:117–49.PubMedGoogle Scholar
  119. 119.
    Elfouly MA, Cook B, Nekola M, Nalbando A. Role of ovum in follicular luteinization. Endocrinology. 1970;87:288–93.Google Scholar
  120. 120.
    Vanderhyden BC, Cohen JN, Morley P. Mouse oocytes regulate granulosa-cell steroidogenesis. Endocrinology. 1993;133:423–6.PubMedGoogle Scholar
  121. 121.
    Vanderhyden BC, Macdonald EA. Mouse oocytes regulate granulosa cell steroidogenesis throughout follicular development. Biol Reprod. 1998;59:1296–301.PubMedGoogle Scholar
  122. 122.
    Spicer LJ, Aad PY, Allen D, Mazerbourg S, Hsueh AJ. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells. J Endocrinol. 2006;189:329–39.PubMedGoogle Scholar
  123. 123.
    Pangas SA, Li X, Robertson EJ, Matzuk MM. Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol. 2006;20:1406–22.PubMedGoogle Scholar
  124. 124.
    Russell DL, Salustri A. Extracellular matrix of the cumulus-oocyte complex. Semin Reprod Med. 2006;24:217–27.PubMedGoogle Scholar
  125. 125.
    Chen L, Russell PT, Larsen WJ. Functional significance of cumulus expansion in the mouse: roles for the preovulatory synthesis of hyaluronic acid within the cumulus mass. Mol Reprod Dev. 1993;34:87–93.PubMedGoogle Scholar
  126. 126.
    Hess KA, Chen L, Larsen WJ. Inter-alpha-inhibitor binding to hyaluronan in the cumulus extracellular matrix is required for optimal ovulation and development of mouse oocytes. Biol Reprod. 1999;61:436–43.PubMedGoogle Scholar
  127. 127.
    Richards JS. Ovulation: new factors that prepare the oocyte for fertilization. Mol Cell Endocrinol. 2005;234:75–9.PubMedGoogle Scholar
  128. 128.
    Hernandez-Gonzalez I, Gonzalez-Robayna I, Shimada M, Wayne CM, Ochsner SA, White L, et al. Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes: does this expand their role in the ovulation process? Mol Endocrinol. 2006;20:1300–21.PubMedGoogle Scholar
  129. 129.
    Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, et al. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol. 2002;16:1154–67.PubMedGoogle Scholar
  130. 130.
    Wang H, Ma W-G, Tejada L, Zhang H, Morrow JD, Das SK, et al. Rescue of female infertility from the loss of cyclooxygenase-2 by compensatory up-regulation of cyclooxygenase-1 is a function of genetic makeup. J Biol Chem. 2004;279:10649–58.PubMedGoogle Scholar
  131. 131.
    Ochsner SA, Day AJ, Rugg MS, Breyer RM, Gomer RH, Richards JS. Disrupted function of tumor necrosis factor-{alpha}-stimulated gene 6 blocks cumulus cell-oocyte complex expansion. Endocrinology. 2003;144:4376–84.PubMedGoogle Scholar
  132. 132.
    Ochsner SA, Russell DL, Day AJ, Breyer RM, Richards JS. Decreased expression of tumor necrosis factor-{alpha}-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology. 2003;144:1008–19.PubMedGoogle Scholar
  133. 133.
    Davis BJ, Lennard DE, Lee CA, Tiano HF, Morham SG, Wetsel WC, et al. Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E(2) and interleukin-1 beta. Endocrinology. 1999;140:2685–95.PubMedGoogle Scholar
  134. 134.
    Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, et al. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell. 1997;91:197–208.PubMedGoogle Scholar
  135. 135.
    Li Q, Rajanahally S, Edson MA, Matzuk MM. Stable expression and characterization of N-terminal tagged recombinant human bone morphogenetic protein 15. Mol Hum Reprod. 2009;15:779–88.PubMedGoogle Scholar
  136. 136.
    Elvin JA, Yan C, Matzuk MM. Growth differentiation factor-9 stimulates progesterone synthesis in granulosa cells via a prostaglandin E2/EP2 receptor pathway. Proc Natl Acad Sci USA. 2000;97:10288–93.PubMedGoogle Scholar
  137. 137.
    Peng XR, Hsueh AJW, Lapolt PS, Bjersing L, Ny T. Localization of luteinizing-hormone receptor messenger-ribonucleic-acid expression in ovarian cell-types during follicle development and ovulation. Endocrinology. 1991;129:3200–7.PubMedGoogle Scholar
  138. 138.
    Hsieh M, Lee D, Panigone S, Homer K, Chen R, Theologis A, et al. Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Mol Cell Biol. 2007;27:1914–24.PubMedGoogle Scholar
  139. 139.
    Shimada M, Hernandez-Gonzalez I, Gonzalez-Robayna I, Richards JS. Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells: key roles for prostaglandin synthase 2 and progesterone receptor. Mol Endocrinol. 2006;20:1352–65.PubMedGoogle Scholar
  140. 140.
    Buccione R, Vanderhyden BC, Caron PJ, Eppig JJ. Fsh-induced expansion of the mouse cumulus-oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev Biol. 1990;138:16–25.PubMedGoogle Scholar
  141. 141.
    Vanderhyden BC. Species differences in the regulation of cumulus expansion by an oocyte-secreted factor(s). J Reprod Fertil. 1993;98:219–27.PubMedGoogle Scholar
  142. 142.
    Prochazka R, Nagyova E, Rimkevicova Z, Nagai T, Kikuchi K, Motlik J. Lack of effect of oocytectomy on expansion of the porcine cumulus. J Reprod Fertil. 1991;93:569–76.PubMedGoogle Scholar
  143. 143.
    Singh B, Zhang X, Armstrong DT. Porcine oocytes release cumulus expansion-enabling activity even though porcine cumulus expansion in vitro is independent of the oocyte. Endocrinology. 1993;132:1860–2.PubMedGoogle Scholar
  144. 144.
    Ralph JH, Telfer EE, Wilmut I. Bovine cumulus cell expansion does not depend on the presence of an oocyte secreted factor. Mol Reprod Dev. 1995;42:248–53.PubMedGoogle Scholar
  145. 145.
    Pangas SA, Matzuk MM. The art and artifact of GDF9 activity: cumulus expansion and the cumulus expansion-enabling factor. Biol Reprod. 2005;73:582–5.PubMedGoogle Scholar
  146. 146.
    Diaz FJ, O’Brien MJ, Wigglesworth K, Eppig JJ. The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion. Dev Biol. 2006;299:91–104.PubMedGoogle Scholar
  147. 147.
    Gui L-M, Joyce IM. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biol Reprod. 2005;72:195–9.PubMedGoogle Scholar
  148. 148.
    Dragovic RA, Ritter LJ, Schulz SJ, Amato F, Armstrong DT, Gilchrist RB. Role of oocyte-secreted growth differentiation factor 9 in the regulation of mouse cumulus expansion. Endocrinology. 2005;146:2798–806.PubMedGoogle Scholar
  149. 149.
    Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000;14:627–44.PubMedGoogle Scholar
  150. 150.
    Roh JS, Bondestam J, Mazerbourg S, Kaivo-Oja N, Groome N, Ritvos O, et al. Growth differentiation factor-9 stimulates inhibin production and activates Smad2 in cultured rat granulosa cells. Endocrinology. 2003;144:172–8.PubMedGoogle Scholar
  151. 151.
    Yi SE, LaPolt PS, Yoon BS, Chen JYC, Lu JKH, Lyons KM. The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci USA. 2001;98:7994–9.PubMedGoogle Scholar
  152. 152.
    Leese HJ, Barton AM. Production of pyruvate by isolated mouse cumulus cells. J Exp Zool. 1985;234:231–6.PubMedGoogle Scholar
  153. 153.
    Biggers JD, Whittingham DG, Donahue RP. The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci USA. 1967;58:560–7.PubMedGoogle Scholar
  154. 154.
    Johnson MT, Freeman EA, Gardner DK, Hunt PA. Oxidative metabolism of pyruvate is required for meiotic maturation of murine oocytes in vivo. Biol Reprod. 2007;77:2–8.PubMedGoogle Scholar
  155. 155.
    Eppig JJ, Pendola FL, Wigglesworth K, Pendola JK. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: amino acid transport. Biol Reprod. 2005;73:351–7.PubMedGoogle Scholar
  156. 156.
    Anderson E, Albertini DF. Gap junctions between oocyte and companion follicle cells in mammalian ovary. J Cell Biol. 1976;71:680–6.PubMedGoogle Scholar
  157. 157.
    O’Shea JD. An ultrastructural study of smooth muscle-like cells in the theca externa of ovarian follicles in the rat. Anat Rec. 1970;167:127–31.PubMedGoogle Scholar
  158. 158.
    Ren Y, Cowan RG, Harman RM, Quirk SM. Dominant activation of the hedgehog signaling pathway in the ovary alters theca development and prevents ovulation. Mol Endocrinol. 2009;23:711–23.PubMedGoogle Scholar
  159. 159.
    Wu X, Chen L, Brown CA, Yan C, Matzuk MM. Interrelationship of growth differentiation factor 9 and inhibin in early folliculogenesis and ovarian tumorigenesis in mice. Mol Endocrinol. 2004;18:1509–19.PubMedGoogle Scholar
  160. 160.
    Solovyeva EV, Hayashi M, Margi K, Barkats C, Klein C, Amsterdam A, et al. Growth differentiation factor-9 stimulates rat theca-interstitial cell androgen biosynthesis. Biol Reprod. 2000;63:1214–8.PubMedGoogle Scholar
  161. 161.
    Spicer LJ, Aad PY, Allen DT, Mazerbourg S, Payne AH, Hsueh AJ. Growth differentiation factor 9 (GDF9) stimulates proliferation and inhibits steroidogenesis by bovine theca cells: influence of follicle size on responses to GDF9. Biol Reprod. 2008;78:243–53.PubMedGoogle Scholar
  162. 162.
    Orisaka M, Jiang JY, Orisaka S, Kotsuji F, Tsang BK. Growth differentiation factor 9 promotes rat preantral follicle growth by up-regulating follicular androgen biosynthesis. Endocrinology. 2009;150:2740–8.PubMedGoogle Scholar
  163. 163.
    Zhang MJ, Su YQ, Sugiura K, Xia GL, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010;330:366–9.PubMedGoogle Scholar
  164. 164.
    Griswold MD, Hogarth CA, Bowles J, Koopman P. Initiating meiosis: the case for retinoic acid. Biol Reprod. 2012;86:35.PubMedGoogle Scholar
  165. 165.
    Vaccari S, Horner K, Mehlmann LM, Conti M. Gene­ration of mouse oocytes defective in cAMP synthesis and degradation: endogenous cyclic AMP is essen­tial for meiotic arrest. Dev Biol. 2008;316:124–34.PubMedGoogle Scholar
  166. 166.
    Vaccari S, Weeks JL, Hsieh M, Menniti FS, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009;81:595–604.PubMedGoogle Scholar
  167. 167.
    Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, et al. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009;136:1869–78.PubMedGoogle Scholar
  168. 168.
    Richard FJ, Tsafriri A, Conti M. Role of phosphodiesterase type 3A in rat oocyte maturation. Biol Reprod. 2001;65:1444–51.PubMedGoogle Scholar
  169. 169.
    Pincus G, Enzmann EV. The comparative behavior of mammalian eggs in vivo and in vitro: I. The activation of ovarian eggs. J Exp Med. 1935;62:665–75.PubMedGoogle Scholar
  170. 170.
    Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ. Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology. 2011;152:4377–85.PubMedGoogle Scholar
  171. 171.
    Kawamura K, Cheng Y, Kawamura N, Takae S, Okada A, Kawagoe Y, et al. Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes. Hum Reprod. 2011;26:3094–101.PubMedGoogle Scholar
  172. 172.
    Eppig JJ, O’Brien MJ, Pendola FL, Watanabe S. Factors affecting the developmental competence of mouse oocytes grown in vitro: follicle-stimulating hormone and insulin. Biol Reprod. 1998;59:1445–53.PubMedGoogle Scholar
  173. 173.
    Tamura H, Takasaki A, Miwa I, Tanoguchi K, Maekawa R, Asada H, et al. Oxidative stress impairs oocyte quality and melatonin protects oocytes from free radical damage and improves fertilization rate. J Pineal Res. 2008;44:280–7.PubMedGoogle Scholar
  174. 174.
    Su YQ, Sugiura K, Eppig JJ. Mouse oocyte control of granulosa cell development and function: paracrine regulation of cumulus cell metabolism. Semin Reprod Med. 2009;27:32–42.PubMedGoogle Scholar
  175. 175.
    McKenzie LJ, Pangas SA, Carson SA, Kovanci E, Cisneros P, Buster JE, et al. Human cumulus granulosa cell gene expression: a predictor of fertilization and embryo selection in women undergoing IVF. Hum Reprod. 2004;19:2869–74.PubMedGoogle Scholar
  176. 176.
    Cillo F, Brevini TAL, Antonini S, Paffoni A, Ragni G, Gandolfi F. Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction. 2007;134:645–50.PubMedGoogle Scholar
  177. 177.
    Rao GD, Tan SL. In vitro maturation of oocytes. Semin Reprod Med. 2005;23:242–7.PubMedGoogle Scholar
  178. 178.
    Suikkari AM. In-vitro maturation: its role in fertility treatment. Curr Opin Obstet Gynecol. 2008;20:242–8.PubMedGoogle Scholar
  179. 179.
    Yeo CX, Gilchrist RB, Thompson JG, Lane M. Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice. Hum Reprod. 2008;23:67–73.PubMedGoogle Scholar
  180. 180.
    Hussein TS, Thompson JG, Gilchrist RB. Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol. 2006;296:514–21.PubMedGoogle Scholar
  181. 181.
    Yeo CX, Gilchrist RB, Lane M. Disruption of bidirectional oocyte-cumulus paracrine signaling during in vitro maturation reduces subsequent mouse oocyte developmental competence. Biol Reprod. 2009;80:1072–80.PubMedGoogle Scholar
  182. 182.
    Pulkki MM, Myllymaaa S, Pasternack A, Lun S, Ludlow H, Al-Qahtani A, et al. The bioactivity of human bone morphogenetic protein-15 is sensitive to C-terminal modification: characterization of the purified untagged processed mature region. Mol Cell Endocrinol. 2011;332:106–15.PubMedGoogle Scholar
  183. 183.
    Simpson CM, Stanton PG, Walton KL, Chan KL, Ritter LJ, Gilchrist RB, et al. Activation of latent human GDF9 by a single residue change (Gly391Arg) in the mature domain. Endocrinology. 2012;153:1301–10.PubMedGoogle Scholar
  184. 184.
    McIntosh CJ, Lun S, Lawrence S, Western AH, McNatty KP, Juengel JL. The proregion of mouse BMP15 regulates the cooperative interactions of BMP15 and GDF9. Biol Reprod. 2008;79:889–96.PubMedGoogle Scholar
  185. 185.
    Mottershead DG, Pulkki MM, Muggalla P, Pasternack A, Tolonen M, Myllymaa S, et al. Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells. Mol Cell Endocrinol. 2008;283:58–67.PubMedGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Departments of Pathology and Immunology, Molecular and Cellular Biology, and Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  2. 2.Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationUSA

Personalised recommendations