Top

Journal of Assisted Reproduction and Genetics

Published in:

01-10-2018 | Review

GDF-9 and BMP-15 direct the follicle symphony

Authors: Alexandra Sanfins, Patrícia Rodrigues, David F. Albertini

Published in: Journal of Assisted Reproduction and Genetics | Issue 10/2018

Abstract

Understanding the physiology underlying the complex dialog between the oocyte and its surrounding somatic cells within the ovarian follicle has been crucial in defining optimal procedures for the development of clinical approaches in ART for women suffering from infertility and ovarian dysfunction. Recent studies have implicated oocyte-secreted factors like growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15), members of the transforming growth factor-beta (TGFβ) superfamily, as potent regulators of folliculogenesis and ovulation. These two factors act as biologically active heterodimers or as homodimers in a synergistic cooperation. Through autocrine and paracrine mechanisms, the GDF-9 and BMP-15 system has been shown to regulate growth, differentiation, and function of granulosa and thecal cells during follicular development playing a vital role in oocyte development, ovulation, fertilization, and embryonic competence. The present mini-review provides an overview of recent findings relating GDF-9 and BMP-15 as fundamental factors implicated in the regulation of ovarian function and discusses their potential role as markers of oocyte quality in women.

Richards JS, Fitzpatrick SL, Clemens JW, Morris JK, Alliston T, Sirois J. Ovarian cell differentiation: a cascade of multiple hormones, cellular signals, and regulated genes. Recent Prog Horm Res. 1995;50:223–54.PubMed

McGinnis LK, Limback SD, Albertini DF. Signaling modalities during oogenesis in mammals. Curr Top Dev Biol. 2013;102:227–42.PubMedCrossRef

Albertini DF, Barrett SL. Oocyte-somatic cell communication. Reprod Suppl. 2003;61:49–54.PubMed

Rodrigues P, Limback D, McGinnis LK, Plancha CE, Albertini DF. Oogenesis: prospects and challenges for the future. J Cell Physiol. 2008;216(2):355–65.PubMedCrossRef

Carabatsos MJ, Sellitto C, Goodenough DA, Albertini DF. Oocyte-granulosa cell heterologous gap junctions are required for the coordination of nuclear and cytoplasmic meiotic competence. Dev Biol. 2000;226(2):167–79.PubMedCrossRef

Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci. 2004;82-83:431–46.PubMedCrossRef

Gougeon A. Regulation of ovarian follicular development in primates: facts and hypotheses. Endocr Rev. 1996;17(2):121–55.PubMedCrossRef

Albertini DF. The Mammalian Oocyte. In: The Mammalian Oocyte, in Knobil and Neill's Physiology of Reproduction (Fourth Edition). Editor: A.Z. Tony Plant; 2015. p. 59–97.CrossRef

Monniaux D. Driving folliculogenesis by the oocyte-somatic cell dialog: lessons from genetic models. Theriogenology. 2016;86(1):41–53.PubMedCrossRef

10.

Falck B. Site of production of oestrogen in rat ovary as studied in micro-transplants. Acta Physiol Scand Suppl. 1959;47(163):1–101.PubMed

11.

el-Fouly MA, et al. Role of the ovum in follicular luteinization. Endocrinology. 1970;87(2):286–93.PubMedCrossRef

12.

Nekola MV, Nalbandov AV. Morphological changes of rat follicular cells as influenced by oocytes. Biol Reprod. 1971;4(2):154–60.PubMedCrossRef

13.

Hutt KJ, Albertini DF. An oocentric view of folliculogenesis and embryogenesis. Reprod BioMed Online. 2007;14(6):758–64.PubMedCrossRef

14.

Erickson GF, Shimasaki S. The role of the oocyte in folliculogenesis. Trends Endocrinol Metab. 2000;11(5):193–8.PubMedCrossRef

15.

Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002;296(5576):2178–80.PubMedCrossRef

16.

Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update. 2008;14(2):159–77.PubMedCrossRef

17.

Eppig JJ. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122(6):829–38.PubMedCrossRef

18.

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(11 Suppl):127–32.PubMed

19.

Hussein TS, Thompson JG, Gilchrist RB. Oocyte-secreted factors enhance oocyte developmental competence. Dev Biol. 2006;296(2):514–21.PubMedCrossRef

20.

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(1):32–42.PubMedPubMedCentralCrossRef

21.

Vanderhyden BC, et al. Evaluation of members of the TGFbeta superfamily as candidates for the oocyte factors that control mouse cumulus expansion and steroidogenesis. Reprod Suppl. 2003;61:55–70.PubMed

22.

Vanderhyden BC, Tonary AM. Differential regulation of progesterone and estradiol production by mouse cumulus and mural granulosa cells by A factor(s) secreted by the oocyte. Biol Reprod. 1995;53(6):1243–50.PubMedCrossRef

23.

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(4):976–84.PubMedCrossRef

24.

Gilchrist RB, et al. Molecular basis of oocyte-paracrine signalling that promotes granulosa cell proliferation. J Cell Sci. 2006;119(Pt 18):3811–21.PubMedCrossRef

25.

Eppig JJ, Pendola FL, Wigglesworth K. Mouse oocytes suppress cAMP-induced expression of LH receptor mRNA by granulosa cells in vitro. Mol Reprod Dev. 1998;49(3):327–32.PubMedCrossRef

26.

Gilchrist RB, Ritter LJ, Armstrong DT. Mouse oocyte mitogenic activity is developmentally coordinated throughout folliculogenesis and meiotic maturation. Dev Biol. 2001;240(1):289–98.PubMedCrossRef

27.

Armstrong DT, Xia P, de Gannes G, Tekpetey FR, Khamsi F. Differential effects of insulin-like growth factor-I and follicle-stimulating hormone on proliferation and differentiation of bovine cumulus cells and granulosa cells. Biol Reprod. 1996;54(2):331–8.PubMedCrossRef

28.

Li R, Norman RJ, Armstrong DT, Gilchrist RB. Oocyte-secreted factor(s) determine functional differences between bovine mural granulosa cells and cumulus cells. Biol Reprod. 2000;63(3):839–45.PubMedCrossRef

29.

Coskun S, Uzumcu M, Lin YC, Friedman CI, Alak BM. Regulation of cumulus cell steroidogenesis by the porcine oocyte and preliminary characterization of oocyte-produced factor(s). Biol Reprod. 1995;53(3):670–5.PubMedCrossRef

30.

Hussein TS, et al. Oocytes prevent cumulus cell apoptosis by maintaining a morphogenic paracrine gradient of bone morphogenetic proteins. J Cell Sci. 2005;118(Pt 22):5257–68.PubMedCrossRef

31.

Knight PG, Glister C. TGF-beta superfamily members and ovarian follicle development. Reproduction. 2006;132(2):191–206.PubMedCrossRef

32.

Chang H, Brown CW, Matzuk MM. Genetic analysis of the mammalian transforming growth factor-beta superfamily. Endocr Rev. 2002;23(6):787–823.PubMedCrossRef

33.

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(2):143–60.PubMedCrossRef

34.

Chang HM, Qiao J, Leung PC. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Hum Reprod Update. 2016;23(1):1–18.PubMedPubMedCentralCrossRef

35.

de Castro FC, Cruz MH, Leal CL. Role of growth differentiation factor 9 and bone morphogenetic protein 15 in ovarian function and their importance in mammalian female fertility - a review. Asian-Australas J Anim Sci. 2016;29(8):1065–74.PubMedCrossRef

36.

Persani L, Rossetti R, di Pasquale E, Cacciatore C, Fabre S. The fundamental role of bone morphogenetic protein 15 in ovarian function and its involvement in female fertility disorders. Hum Reprod Update. 2014;20(6):869–83.PubMedCrossRef

37.

Otsuka F, McTavish KJ, Shimasaki S. Integral role of GDF-9 and BMP-15 in ovarian function. Mol Reprod Dev. 2011;78(1):9–21.PubMedPubMedCentralCrossRef

38.

Shimasaki S, Zachow RJ, Li D, Kim H, Iemura SI, Ueno N, et al. A functional bone morphogenetic protein system in the ovary. Proc Natl Acad Sci U S A. 1999;96(13):7282–7.PubMedPubMedCentralCrossRef

39.

Berisha B, Schams D, Kosmann M, Amselgruber W, Einspanier R. Expression and localisation of vascular endothelial growth factor and basic fibroblast growth factor during the final growth of bovine ovarian follicles. J Endocrinol. 2000;167(3):371–82.PubMedCrossRef

40.

Shimasaki S, Moore RK, Otsuka F, Erickson GF. The bone morphogenetic protein system in mammalian reproduction. Endocr Rev. 2004;25(1):72–101.PubMedCrossRef

41.

McPherron AC, Lee SJ. GDF-3 and GDF-9: two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J Biol Chem. 1993;268(5):3444–9.PubMed

42.

McGrath SA, Esquela AF, Lee SJ. Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol. 1995;9(1):131–6.PubMed

43.

Laitinen M, Vuojolainen K, Jaatinen R, Ketola I, Aaltonen J, Lehtonen E, et al. A novel growth differentiation factor-9 (GDF-9) related factor is co-expressed with GDF-9 in mouse oocytes during folliculogenesis. Mech Dev. 1998;78(1–2):135–40.PubMedCrossRef

44.

Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol. 1998;12(12):1809–17.PubMedCrossRef

45.

Incerti B, Dong J, Borsani G, Matzuk MM. Structure of the mouse growth/differentiation factor 9 gene. Biochim Biophys Acta. 1994;1222(1):125–8.PubMedCrossRef

46.

Ahmad HI, et al. Maximum-likelihood approaches reveal signatures of positive selection in BMP-15 and GDF-9 genes modulating ovarian function in mammalian female fertility, in Ecol Evol. 2017. p. 8895–902.PubMedPubMedCentralCrossRef

47.

Ahmad HI, Ahmad MJ, Adeel MM, Asif AR, du X. Positive selection drives the evolution of endocrine regulatory bone morphogenetic protein system in mammals. Oncotarget. 2018;9(26):18435–45.PubMedPubMedCentralCrossRef

48.

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(1–2):58–67.PubMedCrossRef

49.

Paulini F, Melo EO. The role of oocyte-secreted factors GDF-9 and BMP-15 in follicular development and oogenesis. Reprod Domest Anim. 2011;46(2):354–61.PubMedCrossRef

50.

McIntosh CJ, Lun S, Lawrence S, Western AH, McNatty KP, Juengel JL. The proregion of mouse BMP-15 regulates the cooperative interactions of BMP-15 and GDF-9. Biol Reprod. 2008;79(5):889–96.PubMedCrossRef

51.

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(6):854–66.PubMedCrossRef

52.

Peng J, Li Q, Wigglesworth K, Rangarajan A, Kattamuri C, Peterson RT, et al. Growth differentiation factor 9: bone morphogenetic protein 15 heterodimers are potent regulators of ovarian functions. Proc Natl Acad Sci U S A. 2013;110(8):E776–85.PubMedPubMedCentralCrossRef

53.

Mottershead DG, Sugimura S, al-Musawi SL, Li JJ, Richani D, White MA, et al. Cumulin, an oocyte-secreted heterodimer of the transforming growth factor-beta family, is a potent activator of granulosa cells and improves oocyte quality. J Biol Chem. 2015;290(39):24007–20.PubMedPubMedCentralCrossRef

54.

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: BMP-15 and GDF-9 control cholesterol biosynthesis in cumulus cells. Development. 2008;135(1):111–21.CrossRefPubMed

55.

Sugiura K, Su YQ, Diaz FJ, Pangas SA, Sharma S, Wigglesworth K, et al. Oocyte-derived BMP-15 and FGFs cooperate to promote glycolysis in cumulus cells. Development. 2007;134(14):2593–603.PubMedCrossRef

56.

Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes are required for the preantral granulosa cell to cumulus cell transition in mice. Dev Biol. 2007;305(1):300–11.PubMedPubMedCentralCrossRef

57.

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 U S A. 2005;102(15):5426–31.PubMedPubMedCentralCrossRef

58.

Pangas SA, Matzuk MM. The art and artifact of GDF-9 activity: cumulus expansion and the cumulus expansion-enabling factor. Biol Reprod. 2005;73(4):582–5.PubMedCrossRef

59.

Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci. 2007;120(Pt 8):1330–40.PubMedCrossRef

60.

Ernst EH, Franks S, Hardy K, Villesen P, Lykke-Hartmann K. Granulosa cells from human primordial and primary follicles show differential global gene expression profiles. Hum Reprod. 2018;33(4):666–79.PubMedCrossRef

61.

Chang HM, Cheng JC, Leung PC. Theca-derived BMP4 and BMP7 down-regulate connexin43 expression and decrease gap junction intercellular communication activity in immortalized human granulosa cells. J Clin Endocrinol Metab. 2013;98(3):E437–45.PubMedCrossRef

62.

Chang HM, Cheng JC, Taylor E, Leung PCK. Oocyte-derived BMP-15 but not GDF-9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells. Mol Hum Reprod. 2014;20(5):373–83.PubMedPubMedCentralCrossRef

63.

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(6600):531–5.PubMedCrossRef

64.

Galloway SM, McNatty KP, Cambridge LM, Laitinen MPE, Juengel JL, Jokiranta TS, et al. Mutations in an oocyte-derived growth factor gene (BMP-15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat Genet. 2000;25(3):279–83.PubMedCrossRef

65.

Gueripel X, Brun V, Gougeon A. Oocyte bone morphogenetic protein 15, but not growth differentiation factor 9, is increased during gonadotropin-induced follicular development in the immature mouse and is associated with cumulus oophorus expansion. Biol Reprod. 2006;75(6):836–43.PubMedCrossRef

66.

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(6):1018–34.PubMedCrossRef

67.

Li JJ, et al. Modifications of human growth differentiation factor 9 to improve the generation of embryos from low competence oocytes, in Mol Endocrinol. 2015. p. 40–52.PubMedCrossRef

68.

Hennet ML, Combelles CM. The antral follicle: a microenvironment for oocyte differentiation. Int J Dev Biol. 2012;56(10–12):819–31.PubMedCrossRef

69.

de Caestecker M. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev. 2004;15(1):1–11.PubMedCrossRef

70.

Moore RK, Otsuka F, Shimasaki S. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem. 2003;278(1):304–10.PubMedCrossRef

71.

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(3):653–65.PubMedCrossRef

72.

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(2):473–80.PubMedCrossRef

73.

Mazerbourg S, Hsueh AJ. Genomic analyses facilitate identification of receptors and signalling pathways for growth differentiation factor 9 and related orphan bone morphogenetic protein/growth differentiation factor ligands. Hum Reprod Update. 2006;12(4):373–83.PubMedCrossRef

74.

Franzen P, et al. Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor. Cell. 1993;75(4):681–92.PubMedCrossRef

75.

Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390(6659):465–71.PubMedCrossRef

76.

Miyazawa K, Shinozaki M, Hara T, Furuya T, Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells. 2002;7(12):1191–204.PubMedCrossRef

77.

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 GDF-9+BMP-15-stimulated thymidine uptake by rat granulosa cells. Reproduction. 2011;142(1):123–31.PubMedCrossRef

78.

Mottershead DG, Ritter LJ, Gilchrist RB. Signalling pathways mediating specific synergistic interactions between GDF-9 and BMP-15. Mol Hum Reprod. 2012;18(3):121–8.PubMedCrossRef

79.

Reader KL, Mottershead DG, Martin GA, Gilchrist RB, Heath DA, McNatty KP, et al. Signalling pathways involved in the synergistic effects of human growth differentiation factor 9 and bone morphogenetic protein 15. Reprod Fertil Dev. 2016;28(4):491–8.PubMedCrossRef

80.

Chen H, Liu C, Jiang H, Gao Y, Xu M, Wang J, et al. Regulatory role of miRNA-375 in expression of BMP-15/GDF-9 receptors and its effect on proliferation and apoptosis of bovine cumulus cells. Cell Physiol Biochem. 2017;41(2):439–50.PubMedCrossRef

81.

Liu C, Yuan B, Chen H, Xu M, Sun X, Xu JJ, et al. Effects of MiR-375-BMPR2 as a key factor downstream of BMP-15/GDF-9 on the Smad1/5/8 and Smad2/3 signaling pathways. Cell Physiol Biochem. 2018;46(1):213–25.PubMedCrossRef

82.

Gilchrist RB, Ritter LJ. Differences in the participation of TGFB superfamily signalling pathways mediating porcine and murine cumulus cell expansion. Reproduction. 2011;142(5):647–57.PubMedCrossRef

83.

Chang HM, Cheng JC, Klausen C, Leung PCK. BMP-15 suppresses progesterone production by down-regulating StAR via ALK3 in human granulosa cells. Mol Endocrinol. 2013;27(12):2093–104.PubMedPubMedCentralCrossRef

84.

Albertini DF, et al. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction. 2001;121(5):647–53.PubMedCrossRef

85.

Grondahl ML, et al. Anti-Mullerian hormone remains highly expressed in human cumulus cells during the final stages of folliculogenesis. Reprod BioMed Online. 2011;22(4):389–98.PubMedCrossRef

86.

Dekel N, Kraicer PF. Induction in vitro of mucification of rat cumulus oophorus by gonadotrophins and adenosine 3′,5′-monophosphate. Endocrinology. 1978;102(6):1797–802.PubMedCrossRef

87.

Eppig JJ. Regulation of cumulus oophorus expansion by gonadotropins in vivo and in vitro. Biol Reprod. 1980;23(3):545–52.PubMedCrossRef

88.

Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Update. 2007;13(3):289–312.PubMedCrossRef

89.

Fang L, Cheng JC, Chang HM, Sun YP, Leung PCK. EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in human granulosa cells. J Clin Endocrinol Metab. 2013;98(12):4932–41.PubMedCrossRef

90.

Russell DL, Salustri A. Extracellular matrix of the cumulus-oocyte complex. Semin Reprod Med. 2006;24(4):217–27.PubMedCrossRef

91.

Baranova NS, Inforzato A, Briggs DC, Tilakaratna V, Enghild JJ, Thakar D, et al. Incorporation of pentraxin 3 into hyaluronan matrices is tightly regulated and promotes matrix cross-linking. J Biol Chem. 2014;289(44):30481–98.PubMedPubMedCentralCrossRef

92.

Zhang H, Tian S, Klausen C, Zhu H, Liu R, Leung PCK. Differential activation of noncanonical SMAD2/SMAD3 signaling by bone morphogenetic proteins causes disproportionate induction of hyaluronan production in immortalized human granulosa cells. Mol Cell Endocrinol. 2016;428:17–27.PubMedCrossRef

93.

Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, et al. Mutations in the genes for oocyte-derived growth factors GDF-9 and BMP-15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod. 2004;70(4):900–9.PubMedCrossRef

94.

Wu YT, et al. High bone morphogenetic protein-15 level in follicular fluid is associated with high quality oocyte and subsequent embryonic development. Hum Reprod. 2007;22(6):1526–31.PubMedCrossRef

95.

Gode F, et al. Influence of follicular fluid GDF-9 and BMP-15 on embryo quality. Fertil Steril. 2011;95(7):2274–8.PubMedCrossRef

96.

Clementi C, et al. Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans. PLoS Genet. 2013;9(11):e1003863.PubMedPubMedCentralCrossRef

97.

Nagashima T, et al. BMPR2 is required for postimplantation uterine function and pregnancy maintenance. J Clin Invest. 2013;123(6):2539–50.PubMedPubMedCentralCrossRef

98.

Takebayashi K, et al. Mutation analysis of the growth differentiation factor-9 and -9B genes in patients with premature ovarian failure and polycystic ovary syndrome. Fertil Steril. 2000;74(5):976–9.PubMedCrossRef

99.

Crispi S, et al. Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects. J Cell Physiol. 2013;228(9):1927–34.PubMedCrossRef

100.

Belli M, Shimasaki S. Molecular aspects and clinical relevance of GDF-9 and BMP-15 in ovarian function. Vitam Horm. 2018;107:317–48.PubMedCrossRefPubMedCentral

101.

Tong S, Short RV. Dizygotic twinning as a measure of human fertility. Hum Reprod. 1998;13(1):95–8.PubMedCrossRef

102.

Zhao SY, et al. Expression of growth differentiation factor-9 and bone morphogenetic protein-15 in oocytes and cumulus granulosa cells of patients with polycystic ovary syndrome. Fertil Steril. 2010;94(1):261–7.PubMedCrossRef

103.

Dey SR, et al. Coculturing denuded oocytes during the in vitro maturation of bovine cumulus oocyte complexes exerts a synergistic effect on embryo development. Theriogenology. 2012;77(6):1064–77.PubMedCrossRef

104.

Oocyte-secreted factors in oocyte maturation media enhance subsequent development of bovine cloned embryos - Su - 2014 - Mol Reprod Dev - Wiley Online Library. 2018.

105.

Sudiman J, et al. Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development. J Assist Reprod Genet. 2014;31(3):295–306.PubMedPubMedCentralCrossRef

106.

Yeo CX, et al. Exogenous growth differentiation factor 9 in oocyte maturation media enhances subsequent embryo development and fetal viability in mice. Hum Reprod. 2008;23(1):67–73.PubMedCrossRef

107.

Romaguera R, et al. Oocyte secreted factors improve embryo developmental competence of COCs from small follicles in prepubertal goats. Theriogenology. 2010;74(6):1050–9.PubMedCrossRef

108.

Gomez MN, et al. Effect of oocyte-secreted factors on porcine in vitro maturation, cumulus expansion and developmental competence of parthenotes. Zygote. 2012;20(2):135–45.PubMedCrossRef

109.

Ferrarini E, et al. Clinical characteristics and genetic analysis in women with premature ovarian insufficiency. Maturitas. 2013;74(1):61–7.PubMedCrossRef

110.

Persani L, Rossetti R, Cacciatore C. Genes involved in human premature ovarian failure. J Mol Endocrinol. 2010;45(5):257–79.PubMedCrossRef

111.

Tiotiu D, et al. Variants of the BMP-15 gene in a cohort of patients with premature ovarian failure. Hum Reprod. 2010;25(6):1581–7.PubMedCrossRef

112.

Auclair S, et al. Positive selection in bone morphogenetic protein 15 targets a natural mutation associated with primary ovarian insufficiency in human. PLoS One. 2013;8(10):e78199.PubMedPubMedCentralCrossRef

113.

Di Pasquale E, et al. Identification of new variants of human BMP-15 gene in a large cohort of women with premature ovarian failure. J Clin Endocrinol Metab. 2006;91(5):1976–9.PubMedCrossRef

114.

Kumar R, et al. BMP-15 and GDF-9 gene mutations in premature ovarian failure. J Reprod Infertil. 2017;18(1):185–9.PubMedPubMedCentral

115.

Patino LC, et al. BMP-15 mutations associated with primary ovarian insufficiency reduce expression, activity, or synergy with GDF-9. J Clin Endocrinol Metab. 2017;102(3):1009–19.PubMed

116.

Regan SL, et al. Dysregulation of granulosal bone morphogenetic protein receptor 1B density is associated with reduced ovarian reserve and the age-related decline in human fertility. Mol Cell Endocrinol. 2016;425:84–93.PubMedCrossRef

117.

Salehnia M, Pajokh M, Ghorbanmehr N. Short term organ culture of mouse ovary in the medium supplemented with bone morphogenetic protein 15 and follicle stimulating hormone: a morphological, hormonal and molecular study. J Reprod Infertil. 2016;17(4):199–207.PubMedPubMedCentral

118.

Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biol Reprod. 2012;86(2):27.PubMedCrossRef

Title: GDF-9 and BMP-15 direct the follicle symphony
Authors: Alexandra Sanfins
Patrícia Rodrigues
David F. Albertini
Publication date: 01-10-2018
Publisher: Springer US
Published in: Journal of Assisted Reproduction and Genetics / Issue 10/2018
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI: https://doi.org/10.1007/s10815-018-1268-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GDF-9 and BMP-15 direct the follicle symphony

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 10/2018

Variations in the endometrial receptivity assay (ERA) may actually represent test error

Follicular factors determining granulosa cell number and developmental competence of porcine oocytes

Testing the efficacy and efficiency of a single “universal warming protocol” for vitrified human embryos: prospective randomized controlled trial and retrospective longitudinal cohort study

A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment

In vitro fertilization with granulosa cell tumor: a report of two cases

Assisted reproduction techniques and prenatal diagnosis of Beckwith–Wiedemann spectrum presenting with omphalocele