Skip to main content
SpringerLink
Log in

Growth and differentiation factor 9 promotes oocyte growth at the primary but not the early secondary stage in three-dimensional follicle culture

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Factors that differentially regulate oocyte and granulosa cell growth within the early preantral follicle and how these factors differ at each stage of follicle growth remain poorly understood. The aim of this study was to isolate and evaluate the effect of recombinant growth and differentiation factor 9 (GDF9) on oocyte and granulosa cell growth at the primary and early secondary stages of preantral follicle growth during in vitro culture.

Methods

Primary stage follicles (diameters of 50–89 μm) and early secondary stage follicles (diameters of 90–120 μm) were isolated from immature mice, and individual, intact follicles were cultured in vitro in the presence and absence of recombinant GDF9. The effects of GDF9 on follicle growth were determined by the assessment of changes in the follicle volume during culture. The growth of the granulosa cell and oocyte compartments of the follicles was evaluated separately at each stage.

Results

GDF9 significantly increased the growth of isolated follicles at both the primary and early secondary follicle stages. Independent evaluation of the granulosa cell and oocyte compartments revealed that, while GDF9 promoted granulosa cell growth at both stages of folliculogenesis, oocyte growth was stage specific. GDF9 promoted growth of the oocyte at the primary, but not the early secondary, follicle stage.

Conclusions

These findings demonstrate a stage-specific role for GDF9 in the regulation of oocyte and granulosa cell growth at the primary and early secondary stages of preantral follicle development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Gilchrist RB, Ritter LJ, Armstrong DT. Oocyte-somatic cell interactions during follicle development in mammals. Anim Reprod Sci. 2004;82–83:431–46. doi:10.1016/j.anireprosci.2004.05.017.

    Article  PubMed  Google Scholar 

  3. Oktem O, Urman B. Understanding follicle growth in vivo. Hum Reprod (Oxford, England). 2010;25(12):2944–54. doi:10.1093/humrep/deq275.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci U S A. 2002;99(5):2890–4. doi:10.1073/pnas.052658699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Shimasaki S, Moore RK, Erickson GF, Otsuka F. The role of bone morphogenetic proteins in ovarian function. Reprod Suppl. 2003;61:323–37.

    CAS  PubMed  Google Scholar 

  8. 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. doi:10.1073/pnas.1218020110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sugiura K, Su YQ, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ. Estrogen promotes the development of mouse cumulus cells in coordination with oocyte-derived GDF9 and BMP15. Mol Endocrinol. 2010;24(12):2303–14. doi:10.1210/me.2010-0260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 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(1):111–21. doi:10.1242/dev.009068.

    Article  CAS  PubMed  Google Scholar 

  11. Su YQ, Sugiura K, Li Q, Wigglesworth K, Matzuk MM, Eppig JJ. Mouse oocytes enable LH-induced maturation of the cumulus-oocyte complex via promoting EGF receptor-dependent signaling. Mol Endocrinol. 2010;24(6):1230–9. doi:10.1210/me.2009-0497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. McGrath SA, Esquela AF, Lee SJ. Oocyte-specific expression of growth/differentiation factor-9. Mol Endocrinol. 1995;9(1):131–6. doi:10.1210/mend.9.1.7760846.

    CAS  PubMed  Google Scholar 

  13. Jaatinen R, Laitinen MP, Vuojolainen K, Aaltonen J, Louhio H, Heikinheimo K, et al. Localization of growth differentiation factor-9 (GDF-9) mRNA and protein in rat ovaries and cDNA cloning of rat GDF-9 and its novel homolog GDF-9B. Mol Cell Endocrinol. 1999;156(1–2):189–93.

    Article  CAS  PubMed  Google Scholar 

  14. 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(3):1236–44. doi:10.1210/endo.140.3.6548.

    CAS  PubMed  Google Scholar 

  15. 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.

    CAS  PubMed  Google Scholar 

  16. 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(8):2744–50. doi:10.1210/jcem.84.8.5921.

    CAS  PubMed  Google Scholar 

  17. 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. doi:10.1038/383531a0.

    Article  CAS  PubMed  Google Scholar 

  18. 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(4):900–9. doi:10.1095/biolreprod.103.023093.

    Article  CAS  PubMed  Google Scholar 

  19. Nicol L, Bishop SC, Pong-Wong R, Bendixen C, Holm LE, Rhind SM, et al. Homozygosity for a single base-pair mutation in the oocyte-specific GDF9 gene results in sterility in Thoka sheep. Reproduction. 2009;138(6):921–33. doi:10.1530/REP-09-0193.

    Article  CAS  PubMed  Google Scholar 

  20. Souza CJ, McNeilly AS, Benavides MV, Melo EO, Moraes JC. Mutation in the protease cleavage site of GDF9 increases ovulation rate and litter size in heterozygous ewes and causes infertility in homozygous ewes. Anim Genet. 2014;45(5):732–9. doi:10.1111/age.12190.

    Article  CAS  PubMed  Google Scholar 

  21. Teixeira Filho FL, Baracat EC, Lee TH, Suh CS, Matsui M, Chang RJ, et al. Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(3):1337–44. doi:10.1210/jcem.87.3.8316.

    Article  CAS  PubMed  Google Scholar 

  22. Maciel GA, Baracat EC, Benda JA, Markham SM, Hensinger K, Chang RJ, et al. Stockpiling of transitional and classic primary follicles in ovaries of women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004;89(11):5321–7. doi:10.1210/jc.2004-0643.

    Article  CAS  PubMed  Google Scholar 

  23. Wei LN, Huang R, Li LL, Fang C, Li Y, Liang XY. Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome. J Assist Reprod Genet. 2014. doi:10.1007/s10815-014-0319-8.

    Google Scholar 

  24. Nilsson EE, Skinner MK. Growth and differentiation factor-9 stimulates progression of early primary but not primordial rat ovarian follicle development. Biol Reprod. 2002;67(3):1018–24.

    Article  CAS  PubMed  Google Scholar 

  25. Hornick JE, Duncan FE, Shea LD, Woodruff TK. Multiple follicle culture supports primary follicle growth through paracrine-acting signals. Reproduction. 2013;145(1):19–32. doi:10.1530/REP-12-0233.

    Article  CAS  PubMed  Google Scholar 

  26. 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(Pt 18):3811–21. doi:10.1242/jcs.03105.

    Article  CAS  PubMed  Google Scholar 

  27. Vitt UA, Hayashi M, Klein C, Hsueh AJ. 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(2):370–7.

    Article  CAS  PubMed  Google Scholar 

  28. Liao WX, Moore RK, Shimasaki S. Functional and molecular characterization of naturally occurring mutations in the oocyte-secreted factors bone morphogenetic protein-15 and growth and differentiation factor-9. J Biol Chem. 2004;279(17):17391–6. doi:10.1074/jbc.M401050200.

    Article  CAS  PubMed  Google Scholar 

  29. Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol. 1998;204(2):373–84. doi:10.1006/dbio.1998.9087.

    Article  CAS  PubMed  Google Scholar 

  30. Xu M, Kreeger PK, Shea LD, Woodruff TK. Tissue-engineered follicles produce live, fertile offspring. Tissue Eng. 2006;12(10):2739–46. doi:10.1089/ten.2006.12.2739.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Pangas SA, Saudye H, Shea LD, Woodruff TK. Novel approach for the three-dimensional culture of granulosa cell-oocyte complexes. Tissue Eng. 2003;9(5):1013–21. doi:10.1089/107632703322495655.

    Article  CAS  PubMed  Google Scholar 

  32. Xu M, West E, Shea LD, Woodruff TK. Identification of a stage-specific permissive in vitro culture environment for follicle growth and oocyte development. Biol Reprod. 2006;75(6):916–23. doi:10.1095/biolreprod.106.054833.

    Article  CAS  PubMed  Google Scholar 

  33. West ER, Xu M, Woodruff TK, Shea LD. Physical properties of alginate hydrogels and their effects on in vitro follicle development. Biomaterials. 2007;28(30):4439–48. doi:10.1016/j.biomaterials.2007.07.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shikanov A, Xu M, Woodruff TK, Shea LD. Interpenetrating fibrin-alginate matrices for in vitro ovarian follicle development. Biomaterials. 2009;30(29):5476–85. doi:10.1016/j.biomaterials.2009.06.054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kreeger PK, Deck JW, Woodruff TK, Shea LD. The in vitro regulation of ovarian follicle development using alginate-extracellular matrix gels. Biomaterials. 2006;27(5):714–23. doi:10.1016/j.biomaterials.2005.06.016.

    Article  CAS  PubMed  Google Scholar 

  36. Kreeger PK, Fernandes NN, Woodruff TK, Shea LD. Regulation of mouse follicle development by follicle-stimulating hormone in a three-dimensional in vitro culture system is dependent on follicle stage and dose. Biol Reprod. 2005;73(5):942–50. doi:10.1095/biolreprod.105.042390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Xu J, Xu M, Bernuci MP, Fisher TE, Shea LD, Woodruff TK, et al. Primate follicular development and oocyte maturation in vitro. Adv Exp Med Biol. 2013;761:43–67. doi:10.1007/978-1-4614-8214-7_5.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xu M, West-Farrell ER, Stouffer RL, Shea LD, Woodruff TK, Zelinski MB. Encapsulated three-dimensional culture supports development of nonhuman primate secondary follicles. Biol Reprod. 2009;81(3):587–94. doi:10.1095/biolreprod.108.074732.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Xu M, Barrett SL, West-Farrell E, Kondapalli LA, Kiesewetter SE, Shea LD, et al. In vitro grown human ovarian follicles from cancer patients support oocyte growth. Hum Reprod (Oxford, England). 2009;24(10):2531–40. doi:10.1093/humrep/dep228.

    Article  CAS  Google Scholar 

  40. Xu J, Lawson MS, Yeoman RR, Pau KY, Barrett SL, Zelinski MB, et al. Secondary follicle growth and oocyte maturation during encapsulated three-dimensional culture in rhesus monkeys: effects of gonadotrophins, oxygen and fetuin. Hum Reprod (Oxford, England). 2011;26(5):1061–72. doi:10.1093/humrep/der049.

    Article  CAS  Google Scholar 

  41. Shea LD, Woodruff TK, Shikanov A. Bioengineering the ovarian follicle microenvironment. Annu Rev Biomed Eng. 2014;16:29–52. doi:10.1146/annurev-bioeng-071813-105131.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Hornick JE, Duncan FE, Shea LD, Woodruff TK. Isolated primate primordial follicles require a rigid physical environment to survive and grow in vitro. Hum Reprod (Oxford, England). 2012;27(6):1801–10. doi:10.1093/humrep/der468.

    Article  CAS  Google Scholar 

  43. Eppig JJ, O’Brien MJ. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod. 1996;54(1):197–207.

    Article  CAS  PubMed  Google Scholar 

  44. O’Brien MJ, Pendola JK, Eppig JJ. A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biol Reprod. 2003;68(5):1682–6. doi:10.1095/biolreprod.102.013029.

    Article  PubMed  Google Scholar 

  45. Jin SY, Lei L, Shikanov A, Shea LD, Woodruff TK. A novel two-step strategy for in vitro culture of early-stage ovarian follicles in the mouse. Fertil Steril. 2010;93(8):2633–9. doi:10.1016/j.fertnstert.2009.10.027.

    Article  PubMed  Google Scholar 

  46. Tingen CM, Kiesewetter SE, Jozefik J, Thomas C, Tagler D, Shea L, et al. A macrophage and theca cell-enriched stromal cell population influences growth and survival of immature murine follicles in vitro. Reproduction. 2011;141(6):809–20. doi:10.1530/REP-10-0483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wu MF, Huang WT, Tsay C, Hsu HF, Liu BT, Chiou CM, et al. The stage-dependent inhibitory effect of porcine follicular cells on the development of preantral follicles. Anim Reprod Sci. 2002;73(1–2):73–88.

    Article  CAS  PubMed  Google Scholar 

  48. Itoh T, Hoshi H. Efficient isolation and long-term viability of bovine small preantral follicles in vitro. In Vitro Cell Dev Biol Anim. 2000;36(4):235–40. doi:10.1290/1071-2690(2000)036<0235:EIALTV>2.0.CO;2.

    Article  CAS  PubMed  Google Scholar 

  49. Laronda MM, Duncan FE, Hornick JE, Xu M, Pahnke JE, Whelan KA, et al. Alginate encapsulation supports the growth and differentiation of human primordial follicles within ovarian cortical tissue. J Assist Reprod Genet. 2014;31(8):1013–28. doi:10.1007/s10815-014-0252-x.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Tagler D, Tu T, Smith RM, Anderson NR, Tingen CM, Woodruff TK, et al. Embryonic fibroblasts enable the culture of primary ovarian follicles within alginate hydrogels. Tissue Eng A. 2012;18(11–12):1229–38. doi:10.1089/ten.TEA.2011.0418.

    Article  CAS  Google Scholar 

  51. Tagler D, Makanji Y, Anderson NR, Woodruff TK, Shea LD. Supplemented alphaMEM/F12-based medium enables the survival and growth of primary ovarian follicles encapsulated in alginate hydrogels. Biotechnol Bioeng. 2013;110(12):3258–68. doi:10.1002/bit.24986.

    Article  CAS  PubMed  Google Scholar 

  52. 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(2):329–39. doi:10.1677/joe.1.06503.

    Article  CAS  PubMed  Google Scholar 

  53. Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010;330(6002):366–9. doi:10.1126/science.1193573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Watson LN, Mottershead DG, Dunning KR, Robker RL, Gilchrist RB, Russell DL. Heparan sulfate proteoglycans regulate responses to oocyte paracrine signals in ovarian follicle morphogenesis. Endocrinology. 2012;153(9):4544–55. doi:10.1210/en.2012-1181.

    Article  CAS  PubMed  Google Scholar 

  55. Pedersen T, Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J Reprod Fertil. 1968;17(3):555–7.

    Article  CAS  PubMed  Google Scholar 

  56. Gilchrist RB, Ritter LJ, Cranfield M, Jeffery LA, Amato F, Scott SJ, et al. Immunoneutralization of growth differentiation factor 9 reveals it partially accounts for mouse oocyte mitogenic activity. Biol Reprod. 2004;71(3):732–9. doi:10.1095/biolreprod.104.028852.

    Article  CAS  PubMed  Google Scholar 

  57. Gueripel X, Benahmed M, Gougeon A. Sequential gonadotropin treatment of immature mice leads to amplification of transforming growth factor beta action, via upregulation of receptor-type 1, Smad 2 and 4, and downregulation of Smad 6. Biol Reprod. 2004;70(3):640–8. doi:10.1095/biolreprod.103.021162.

    Article  CAS  PubMed  Google Scholar 

  58. Sun RZ, Lei L, Cheng L, Jin ZF, Zu SJ, Shan ZY, et al. Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles. J Mol Histol. 2010;41(6):325–32. doi:10.1007/s10735-010-9294-2.

    Article  CAS  PubMed  Google Scholar 

  59. Feary ES, Juengel JL, Smith P, French MC, O’Connell AR, Lawrence SB, et al. Patterns of expression of messenger RNAs encoding GDF9, BMP15, TGFBR1, BMPR1B, and BMPR2 during follicular development and characterization of ovarian follicular populations in ewes carrying the Woodlands FecX2W mutation. Biol Reprod. 2007;77(6):990–8. doi:10.1095/biolreprod.107.062752.

    Article  CAS  PubMed  Google Scholar 

  60. Paradis F, Novak S, Murdoch GK, Dyck MK, Dixon WT, Foxcroft GR. Temporal regulation of BMP2, BMP6, BMP15, GDF9, BMPR1A, BMPR1B, BMPR2 and TGFBR1 mRNA expression in the oocyte, granulosa and theca cells of developing preovulatory follicles in the pig. Reproduction. 2009;138(1):115–29. doi:10.1530/REP-08-0538.

    Article  CAS  PubMed  Google Scholar 

  61. Oron G, Fisch B, Ao A, Zhang XY, Farhi J, Ben-Haroush A, et al. Expression of growth-differentiating factor 9 and its type 1 receptor in human ovaries. Reprod Biomed Online. 2010;21(1):109–17. doi:10.1016/j.rbmo.2010.03.011.

    Article  CAS  PubMed  Google Scholar 

  62. Li Q, Agno JE, Edson MA, Nagaraja AK, Nagashima T, Matzuk MM. Transforming growth factor beta receptor type 1 is essential for female reproductive tract integrity and function. PLoS Genet. 2011;7(10):e1002320. doi:10.1371/journal.pgen.1002320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 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. doi:10.1210/me.2003-0393.

    Article  CAS  PubMed  Google Scholar 

  64. 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(1):271–8. doi:10.1210/jc.2004-1288.

    Article  CAS  PubMed  Google Scholar 

  65. Vitt UA, Mazerbourg S, Klein C, Hsueh AJ. Bone morphogenetic protein receptor type II is a receptor for growth differentiation factor-9. Biol Reprod. 2002;67(2):473–80.

    Article  CAS  PubMed  Google Scholar 

  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. doi:10.1210/mend.13.6.0309.

    Article  CAS  PubMed  Google Scholar 

  67. Packer AI, Hsu YC, Besmer P, Bachvarova RF. The ligand of the c-kit receptor promotes oocyte growth. Dev Biol. 1994;161(1):194–205. doi:10.1006/dbio.1994.1020.

    Article  PubMed  Google Scholar 

  68. Manova K, Huang EJ, Angeles M, De Leon V, Sanchez S, Pronovost SM, et al. The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor in oocyte growth and in proliferation of spermatogonia. Dev Biol. 1993;157(1):85–99. doi:10.1006/dbio.1993.1114.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Teresa Woodruff and Dr. Min Xu for their advice regarding follicle isolation, encapsulation, and culture and for their gifts of alginate and fetuin reagents.

Author information

Authors and Affiliations

  1. Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, CA, 92093-0633, USA

    Heidi Cook-Andersen, Kirsten J. Curnow, H. Irene Su, R. Jeffrey Chang & Shunichi Shimasaki

Authors
  1. Heidi Cook-Andersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kirsten J. Curnow
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Irene Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Jeffrey Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shunichi Shimasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Heidi Cook-Andersen or Shunichi Shimasaki.

Ethics declarations

The University of California, San Diego, Institutional Animal Care and Use Committee approved all animal protocols.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This research was funded by a Pilot Study Project from the Oncofertility Consortium: Fertility Preservation for Women (U54 RR024347), the National Institutes of Health (NIH) grant R01 HD41494 and the National Institute of Child Health and Human Development/NIH through a cooperative agreement (U54 HD012303) as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research. Dr. Cook-Andersen was supported by the Women’s Reproductive Health Research grant K12 HD001259.

Additional information

Capsule

These findings demonstrate a stage-specific role for GDF9 in the regulation of oocyte and granulosa cell growth at the primary and early secondary stages of preantral follicle development.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cook-Andersen, H., Curnow, K.J., Su, H.I. et al. Growth and differentiation factor 9 promotes oocyte growth at the primary but not the early secondary stage in three-dimensional follicle culture. J Assist Reprod Genet 33, 1067–1077 (2016). https://doi.org/10.1007/s10815-016-0719-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-016-0719-z

Keywords

Search

Navigation