Oogenesis pp 109-126 | Cite as

The Quest for Oogenesis (Folliculogenesis) In Vitro

  • Sergio Romero
  • Sandra Sanfilippo
  • Johan SmitzEmail author


Because of the improvements in efficacy of cancer treatments, the rates of cancer survivors are constantly increasing; however some of these more aggressive anti-cancer therapies endanger fertility.

Although the use of classical Assisted reproduction techniques, like in vitro fertilisation (IVF) and embryo freezing/transfer (Frozen embryo transfer, FRET), are an option for certain adult patients, these techniques depend on the amount of oocytes obtained after controlled ovarian stimulation. This treatment is not suitable for children or adolescent patients, and potentially unsafe when using it in breast cancer patients. Therefore, adolescent and adult female cancer patients are being offered the possibility to cryopreserve pieces of their ovarian tissue with the ultimate goal of restoring their fertility when they are disease free.

Ovarian tissue grafting has proven successful, however the latent risk for reintroducing malignant cells, enforces the search for alternatives. In vitro culture of cryopreserved tissue, and of ovarian follicles isolated from this tissue, are challenging alternatives. Techniques for culturing ovarian tissue and follicles are under development and may benefit from advances in molecular techniques, innovative culture devices and artificial extracellular matrices.

This review focuses on state-of-the-art culturing techniques for ovarian follicles and reports on the most recent advances in the field in animal models and in human.


Folliculogenesis Oogenesis Follicle Oocyte Follicle culture Oocyte competence 



The Belgian Foundation Against Cancer (Project No. 221.2008).

Agentschap voor Innovatie door Wetenschap en Technologie (Project No. 70719).


  1. 1.
    Schmidt KT, Rosendahl M, Ernst E, Loft A, Andersen AN, Dueholm M, et al. Autotransplantation of cryopreserved ovarian tissue in 12 women with chemotherapy-induced premature ovarian failure: the Danish experience. Fertil Steril. 2011;95(2):695–701 [Evaluation Studies Multicenter Study Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  2. 2.
    Dolmans MM, Marinescu C, Saussoy P, Van Langendonckt A, Amorim C, Donnez J. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood. 2010;116(16):2908–14 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  3. 3.
    Newton H, Picton H, Gosden RG. In vitro growth of oocyte-granulosa cell complexes isolated from cryopreserved ovine tissue. J Reprod Fertil. 1999;115(1):141–50 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  4. 4.
    Newton H, Illingworth P. In-vitro growth of murine pre-antral follicles after isolation from cryopreserved ovarian tissue. Hum Reprod. 2001;16(3):423–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Xu M, Banc A, Woodruff TK, Shea LD. Secondary follicle growth and oocyte maturation by culture in alginate hydrogel following cryopreservation of the ovary or individual follicles. Biotechnol Bioeng. 2009;103(2):378–86 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  6. 6.
    Castro SV, de Carvalho AA, da Silva CM, Faustino LR, Campello CC, Lucci CM, et al. Freezing solution containing dimethylsulfoxide and fetal calf serum maintains survival and ultrastructure of goat preantral follicles after cryopreservation and in vitro culture of ovarian tissue. Cell Tissue Res. 2011;346(2):283–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Dorphin B, Prades-Borio M, Anastacio A, Rojat P, Coussieu C, Poirot C. Secretion profiles from in vitro cultured follicles, isolated from fresh prepubertal and adult mouse ovaries or frozen-thawed prepubertal mouse ovaries. Zygote. 2011;11:1–12.Google Scholar
  8. 8.
    Ting AY, Yeoman RR, Lawson MS, Zelinski MB. In vitro development of secondary follicles from cryopreserved rhesus macaque ovarian tissue after slow-rate freeze or vitrification. Hum Reprod. 2011;26(9):2461–72 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  9. 9.
    Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, et al. Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum Reprod Update. 2010;16(4):395–414 [Research Support, N.I.H., Extramural Review].PubMedCrossRefGoogle Scholar
  10. 10.
    Diaz FJ, Wigglesworth K, Eppig JJ. Oocytes determine cumulus cell lineage in mouse ovarian follicles. J Cell Sci. 2007;120(Pt 8):1330–40 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  11. 11.
    Sugiura K, Pendola FL, Eppig JJ. Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Dev Biol. 2005;279(1):20–30 [Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  12. 12.
    Zlotkin T, Farkash Y, Orly J. Cell-specific expression of immunoreactive cholesterol side-chain cleavage cytochrome P-450 during follicular development in the rat ovary. Endocrinology. 1986;119(6):2809–20 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.].PubMedCrossRefGoogle Scholar
  13. 13.
    Ishimura K, Yoshinaga-Hirabayashi T, Tsuri H, Fujita H, Osawa Y. Further immunocytochemical study on the localization of aromatase in the ovary of rats and mice. Histochemistry. 1989;90(6):413–6 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S].PubMedCrossRefGoogle Scholar
  14. 14.
    Vanderhyden BC, Cohen JN, Morley P. Mouse oocytes regulate granulosa cell steroidogenesis. Endocrinology. 1993;133(1):423–6 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  15. 15.
    Henderson KM, Moon YS. Luteinization of bovine granulosa cells and corpus luteum formation associated with loss of androgen-aromatizing ability. J Reprod Fertil. 1979;56(1):89–97.PubMedCrossRefGoogle Scholar
  16. 16.
    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 [Comparative Study Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  17. 17.
    Mintz B. Embryological phases of mammalian gametogenesis. J Cell Comp Physiol. 1960;56:31–47.PubMedCrossRefGoogle Scholar
  18. 18.
    Mandl AM. Pre-ovulatory changes in the oocyte of the adult rat. Proc R Soc Lond B Biol Sci. 1963;158(970):105–18.CrossRefGoogle Scholar
  19. 19.
    Byskov AG. Differentiation of mammalian embryonic gonad. Physiol Rev. 1986;66(1):71–117.PubMedGoogle Scholar
  20. 20.
    Szybek K. In-vitro maturation of oocytes from sexually immature mice. J Endocrinol. 1972;54(3):527–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Durinzi KL, Saniga EM, Lanzendorf SE. The relationship between size and maturation in vitro in the unstimulated human oocyte. Fertil Steril. 1995;63(2):404–6.PubMedGoogle Scholar
  22. 22.
    Ducibella T, Buetow J. Competence to undergo normal, fertilization-induced cortical activation develops after metaphase I of meiosis in mouse oocytes. Dev Biol. 1994;165(1):95–104.PubMedCrossRefGoogle Scholar
  23. 23.
    Ducibella T. The cortical reaction and development of activation competence in mammalian oocytes. Hum Reprod Update. 1996;2(1):29–42.PubMedCrossRefGoogle Scholar
  24. 24.
    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(6):1445–53.PubMedCrossRefGoogle Scholar
  25. 25.
    Abbott AL, Fissore RA, Ducibella T. Identification of a translocation deficiency in cortical granule secretion in preovulatory mouse oocytes. Biol Reprod. 2001;65(6):1640–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Ducibella T, Schultz RM, Ozil JP. Role of calcium signals in early development. Semin Cell Dev Biol. 2006;17(2):324–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Ajduk A, Malagocki A, Maleszewski M. Cytoplasmic maturation of mammalian oocytes: development of a mechanism responsible for sperm-induced Ca2+ oscillations. Reprod Biol. 2008;8(1):3–22.PubMedCrossRefGoogle Scholar
  28. 28.
    Abbott AL, Ducibella T. Calcium and the control of mammalian cortical granule exocytosis. Front Biosci. 2001;6:D792–806 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review].PubMedCrossRefGoogle Scholar
  29. 29.
    Smitz JE, Cortvrindt RG. The earliest stages of folliculogenesis in vitro. Reproduction. 2002;123(2):185–202.PubMedCrossRefGoogle Scholar
  30. 30.
    Yoshida H, Takakura N, Kataoka H, Kunisada T, Okamura H, Nishikawa SI. Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development. Dev Biol. 1997;184(1):122–37.PubMedCrossRefGoogle Scholar
  31. 31.
    Driancourt MA, Reynaud K, Cortvrindt R, Smitz J. Roles of KIT and KIT LIGAND in ovarian function. Rev Reprod. 2000;5(3):143–52.PubMedCrossRefGoogle Scholar
  32. 32.
    Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, et al. Control of primordial follicle recruitment by anti-mullerian hormone in the mouse ovary. Endocrinology. 1999;140(12):5789–96.PubMedCrossRefGoogle Scholar
  33. 33.
    Abir R, Roizman P, Fisch B, Nitke S, Okon E, Orvieto R, et al. Pilot study of isolated early human follicles cultured in collagen gels for 24 hours. Hum Reprod. 1999;14(5):1299–301.PubMedCrossRefGoogle Scholar
  34. 34.
    Abir R, Fisch B, Nitke S, Okon E, Raz A, Ben Rafael Z. Morphological study of fully and partially isolated early human follicles. Fertil Steril. 2001;75(1):141–6 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  35. 35.
    Miyano T. Bringing up small oocytes to eggs in pigs and cows. Theriogenology. 2003;59(1):61–72.PubMedCrossRefGoogle Scholar
  36. 36.
    Muruvi W, Picton HM, Rodway RG, Joyce IM. In vitro growth of oocytes from primordial follicles isolated from frozen-thawed lamb ovaries. Theriogenology. 2005;64(6):1357–70.PubMedCrossRefGoogle Scholar
  37. 37.
    Vanacker J, Camboni A, Dath C, Van Langendonckt A, Dolmans MM, Donnez J, et al. Enzymatic isolation of human primordial and primary ovarian follicles with Liberase DH: protocol for application in a clinical setting. Fertil Steril. 2011;96(2):379–83.e3.PubMedCrossRefGoogle Scholar
  38. 38.
    Hovatta O, Wright C, Krausz T, Hardy K, Winston RM. Human primordial, primary and secondary ovarian follicles in long-term culture: effect of partial isolation. Hum Reprod. 1999;14(10):2519–24.PubMedCrossRefGoogle Scholar
  39. 39.
    Honda A, Hirose M, Hara K, Matoba S, Inoue K, Miki H, et al. Isolation, characterization, and in vitro and in vivo differentiation of putative thecal stem cells. Proc Natl Acad Sci USA. 2007;104(30):12389–94.PubMedCrossRefGoogle Scholar
  40. 40.
    Honda A, Hirose M, Inoue K, Hiura H, Miki H, Ogonuki N, et al. Large-scale production of growing oocytes in vitro from neonatal mouse ovaries. Int J Dev Biol. 2009;53(4):605–13.PubMedCrossRefGoogle Scholar
  41. 41.
    Eppig JJ, O’Brien MJ. Development in vitro of mouse oocytes from primordial follicles. Biol Reprod. 1996;54(1):197–207.PubMedCrossRefGoogle Scholar
  42. 42.
    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.PubMedCrossRefGoogle Scholar
  43. 43.
    Parrott JA, Skinner MK. Kit-ligand/stem cell factor induces primordial follicle development and ­initiates folliculogenesis. Endocrinology. 1999;140(9):4262–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Sadeu JC, Adriaenssens T, Smitz J. Expression of growth differentiation factor 9, bone morphogenetic protein 15, and anti-mullerian hormone in cultured mouse primary follicles. Reproduction. 2008;136(2):195–203.PubMedCrossRefGoogle Scholar
  45. 45.
    Fortune JE, Kito S, Wandji SA, Srsen V. Activation of bovine and baboon primordial follicles in vitro. Theriogenology. 1998;49(2):441–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Gigli I, Byrd DD, Fortune JE. Effects of oxygen tension and supplements to the culture medium on activation and development of bovine follicles in vitro. Theriogenology. 2006;66(2):344–53.PubMedCrossRefGoogle Scholar
  47. 47.
    McLaughlin M, Telfer EE. Oocyte development in bovine primordial follicles is promoted by activin and FSH within a two-step serum-free culture system. Reproduction. 2010;139(6):971–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Hovatta O, Silye R, Abir R, Krausz T, Winston RM. Extracellular matrix improves survival of both stored and fresh human primordial and primary ovarian follicles in long-term culture. Hum Reprod. 1997;12(5):1032–6 [Comparative Study].PubMedCrossRefGoogle Scholar
  49. 49.
    Carlsson IB, Scott JE, Visser JA, Ritvos O, Themmen AP, Hovatta O. Anti-mullerian hormone inhibits initiation of growth of human primordial ovarian follicles in vitro. Hum Reprod. 2006;21(9):2223–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Sadeu JC, Smitz J. Growth differentiation factor-9 and anti-mullerian hormone expression in cultured human follicles from frozen-thawed ovarian tissue. Reprod Biomed Online. 2008;17(4):537–48.PubMedCrossRefGoogle Scholar
  51. 51.
    Telfer EE, McLaughlin M, Ding C, Thong KJ. A two-step serum-free culture system supports development of human oocytes from primordial follicles in the presence of activin. Hum Reprod. 2008;23(5):1151–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Silva JR, van den Hurk R, Costa SH, Andrade ER, Nunes AP, Ferreira FV, et al. Survival and growth of goat primordial follicles after in vitro culture of ovarian cortical slices in media containing coconut water. Anim Reprod Sci. 2004;81(3–4):273–86.PubMedCrossRefGoogle Scholar
  53. 53.
    Murray AA, Molinek MD, Baker SJ, Kojima FN, Smith MF, Hillier SG, et al. Role of ascorbic acid in promoting follicle integrity and survival in intact mouse ovarian follicles in vitro. Reproduction. 2001;121(1):89–96 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  54. 54.
    Thomas FH, Leask R, Srsen V, Riley SC, Spears N, Telfer EE. Effect of ascorbic acid on health and morphology of bovine preantral follicles during long-term culture. Reproduction. 2001;122(3):487–95 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  55. 55.
    Rossetto R, Lima-Verde IB, Matos MH, Saraiva MV, Martins FS, Faustino LR, et al. Interaction between ascorbic acid and follicle-stimulating hormone maintains follicular viability after long-term in vitro culture of caprine preantral follicles. Domest Anim Endocrinol. 2009;37(2):112–23 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  56. 56.
    Gougeon A. Dynamics of follicular growth in the human: a model from preliminary results. Hum Reprod. 1986;1(2):81–7.PubMedGoogle Scholar
  57. 57.
    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 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  58. 58.
    Wandji SA, Srsen V, Voss AK, Eppig JJ, Fortune JE. Initiation in vitro of growth of bovine primordial follicles. Biol Reprod. 1996;55(5):942–8 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  59. 59.
    Wandji SA, Srsen V, Nathanielsz PW, Eppig JJ, Fortune JE. Initiation of growth of baboon primordial follicles in vitro. Hum Reprod. 1997;12(9):1993–2001 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  60. 60.
    Albertini DF, Combelles CM, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction. 2001;121(5):647–53 [Review].PubMedCrossRefGoogle Scholar
  61. 61.
    Skinner MK. Regulation of primordial follicle assembly and development. Hum Reprod Update. 2005;11(5):461–71.PubMedCrossRefGoogle Scholar
  62. 62.
    Nilsson E, Parrott JA, Skinner MK. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol. 2001;175(1–2):123–30.PubMedCrossRefGoogle Scholar
  63. 63.
    Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol. 2002;188(1–2):65–73.PubMedCrossRefGoogle Scholar
  64. 64.
    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.PubMedCrossRefGoogle Scholar
  65. 65.
    Fortune JE. The early stages of follicular development: activation of primordial follicles and growth of preantral follicles. Anim Reprod Sci. 2003;78(3–4):135–63 [Review].PubMedCrossRefGoogle Scholar
  66. 66.
    Nilsson EE, Skinner MK. Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol Reprod. 2003;69(4):1265–72.PubMedCrossRefGoogle Scholar
  67. 67.
    Nilsson EE, Skinner MK. Kit ligand and basic fibroblast growth factor interactions in the induction of ovarian primordial to primary follicle transition. Mol Cell Endocrinol. 2004;214(1–2):19–25.PubMedCrossRefGoogle Scholar
  68. 68.
    Kezele P, Nilsson EE, Skinner MK. Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. Biol Reprod. 2005;73(5):967–73.PubMedCrossRefGoogle Scholar
  69. 69.
    Nilsson EE, Detzel C, Skinner MK. Platelet-derived growth factor modulates the primordial to primary follicle transition. Reproduction. 2006;131(6):1007–15.PubMedCrossRefGoogle Scholar
  70. 70.
    Martins FS, Celestino JJ, Saraiva MV, Matos MH, Bruno JB, Rocha-Junior CM, et al. Growth and differentiation factor-9 stimulates activation of goat ­primordial follicles in vitro and their progression to secondary follicles. Reprod Fertil Dev. 2008;20(8):916–24.PubMedCrossRefGoogle Scholar
  71. 71.
    da Nobrega JE, Goncalves PB, Chaves RN, Magalhaes DD, Rossetto R, Lima-Verde IB, et al. Leukemia inhibitory factor stimulates the transition of primordial to primary follicle and supports the goat primordial follicle viability in vitro. Zygote. 2011;18:1–6.Google Scholar
  72. 72.
    Ding CC, Thong KJ, Krishna A, Telfer EE. Activin A inhibits activation of human primordial follicles in vitro. J Assist Reprod Genet. 2010;27(4):141–7 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  73. 73.
    Kedem A, Fisch B, Garor R, Ben-Zaken A, Gizunterman T, Felz C, et al. Growth differentiating factor 9 (GDF9) and bone morphogenetic protein 15 both activate development of human primordial follicles in vitro, with seemingly more beneficial effects of GDF9. J Clin Endocrinol Metab. 2011;96(8):E1246–54 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  74. 74.
    Adhikari D, Liu K. Molecular mechanisms underlying the activation of mammalian primordial follicles. Endocr Rev. 2009;30(5):438–64.PubMedCrossRefGoogle Scholar
  75. 75.
    Liu K, Rajareddy S, Liu L, Jagarlamudi K, Boman K, Selstam G, et al. Control of mammalian oocyte growth and early follicular development by the oocyte PI3 kinase pathway: new roles for an old timer. Dev Biol. 2006;299(1):1–11.PubMedCrossRefGoogle Scholar
  76. 76.
    Reddy P, Shen L, Ren C, Boman K, Lundin E, Ottander U, et al. Activation of Akt (PKB) and suppression of FKHRL1 in mouse and rat oocytes by stem cell factor during follicular activation and development. Dev Biol. 2005;281(2):160–70.PubMedCrossRefGoogle Scholar
  77. 77.
    Maehama T, Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1998;273(22):13375–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Liu K. Stem cell factor (SCF)-kit mediated phosphatidylinositol 3 (PI3) kinase signaling during mammalian oocyte growth and early follicular development. Front Biosci. 2006;11:126–35.PubMedCrossRefGoogle Scholar
  79. 79.
    Arden KC, Biggs 3rd WH. Regulation of the FoxO family of transcription factors by phosphatidylinositol-3 kinase-activated signaling. Arch Biochem Biophys. 2002;403(2):292–8.PubMedCrossRefGoogle Scholar
  80. 80.
    Thomas FH, Ismail RS, Jiang JY, Vanderhyden BC. Kit ligand 2 promotes murine oocyte growth in vitro. Biol Reprod. 2008;78(1):167–75.PubMedCrossRefGoogle Scholar
  81. 81.
    Zhang P, Chao H, Sun X, Li L, Shi Q, Shen W. Murine folliculogenesis in vitro is stage-specifically regulated by insulin via the Akt signaling pathway. Histochem Cell Biol. 2010;134(1):75–82.PubMedCrossRefGoogle Scholar
  82. 82.
    Louhio H, Hovatta O, Sjoberg J, Tuuri T. The effects of insulin, and insulin-like growth factors I and II on human ovarian follicles in long-term culture. Mol Hum Reprod. 2000;6(8):694–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Wright CS, Hovatta O, Margara R, Trew G, Winston RM, Franks S, et al. Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles. Hum Reprod. 1999;14(6):1555–62.PubMedCrossRefGoogle Scholar
  84. 84.
    Li J, Kawamura K, Cheng Y, Liu S, Klein C, Duan EK, et al. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci USA. 2010;107(22):10280–4.PubMedCrossRefGoogle Scholar
  85. 85.
    Matos MH, Bruno JB, Rocha RM, Lima-Verde IB, Santos KD, Saraiva MV, et al. In vitro development of primordial follicles after long-term culture of goat ovarian tissue. Res Vet Sci. 2011;90(3):404–11.PubMedCrossRefGoogle Scholar
  86. 86.
    Fortune JE, Kito S, Byrd DD. Activation of primordial follicles in vitro. J Reprod Fertil Suppl. 1999;54:439–48.PubMedGoogle Scholar
  87. 87.
    Oktay K, Briggs D, Gosden RG. Ontogeny of follicle-stimulating hormone receptor gene expression in isolated human ovarian follicles. J Clin Endocrinol Metab. 1997;82(11):3748–51.PubMedCrossRefGoogle Scholar
  88. 88.
    Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000;14(6):627–44.PubMedGoogle Scholar
  89. 89.
    Durlinger AL, Gruijters MJ, Kramer P, Karels B, Ingraham HA, Nachtigal MW, et al. Anti-mullerian hormone inhibits initiation of primordial follicle growth in the mouse ovary. Endocrinology. 2002;143(3):1076–84.PubMedCrossRefGoogle Scholar
  90. 90.
    Schmidt KL, Kryger-Baggesen N, Byskov AG, Andersen CY. Anti-mullerian hormone initiates growth of human primordial follicles in vitro. Mol Cell Endocrinol. 2005;234(1–2):87–93.PubMedCrossRefGoogle Scholar
  91. 91.
    Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJ, 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(1):316–21.PubMedCrossRefGoogle Scholar
  92. 92.
    Wang J, Roy SK. Growth differentiation factor-9 and stem cell factor promote primordial follicle formation in the hamster: modulation by follicle-stimulating hormone. Biol Reprod. 2004;70(3):577–85.PubMedCrossRefGoogle Scholar
  93. 93.
    Lee WS, Yoon SJ, Yoon TK, Cha KY, Lee SH, Shimasaki S, et al. Effects of bone morphogenetic protein-7 (BMP-7) on primordial follicular growth in the mouse ovary. Mol Reprod Dev. 2004;69(2):159–63.PubMedCrossRefGoogle Scholar
  94. 94.
    Bristol-Gould SK, Kreeger PK, Selkirk CG, Kilen SM, Cook RW, Kipp JL, et al. Postnatal regulation of germ cells by activin: the establishment of the initial follicle pool. Dev Biol. 2006;298(1):132–48 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  95. 95.
    Hulshof SC, Figueiredo JR, Beckers JF, Bevers MM, Vanderstichele H, van den Hurk R. Bovine preantral follicles and activin: immunohistochemistry for activin and activin receptor and the effect of bovine activin A in vitro. Theriogenology. 1997;48(1):133–42.PubMedCrossRefGoogle Scholar
  96. 96.
    Trounson A, Anderiesz C, Jones G. Maturation of human oocytes in vitro and their developmental competence. Reproduction. 2001;121(1):51–75 [Review].PubMedCrossRefGoogle Scholar
  97. 97.
    Kim DH, Ko DS, Lee HC, Lee HJ, Park WI, Kim SS, et al. Comparison of maturation, fertilization, development, and gene expression of mouse oocytes grown in vitro and in vivo. J Assist Reprod Genet. 2004;21(7):233–40 [Comparative Study].PubMedCrossRefGoogle Scholar
  98. 98.
    Combelles CM, Fissore RA, Albertini DF, Racowsky C. In vitro maturation of human oocytes and cumulus cells using a co-culture three-dimensional collagen gel system. Hum Reprod. 2005;20(5):1349–58 [Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, Non-P.H.S. Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  99. 99.
    Eppig JJ, O’Brien MJ, Wigglesworth K, Nicholson A, Zhang W, King BA. Effect of in vitro maturation of mouse oocytes on the health and lifespan of adult offspring. Hum Reprod. 2009;24(4):922–8 [In Vitro Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  100. 100.
    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 [Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  101. 101.
    Latham KE, Bautista FD, Hirao Y, O’Brien MJ, Eppig JJ. Comparison of protein synthesis patterns in mouse cumulus cells and mural granulosa cells: effects of follicle-stimulating hormone and insulin on granulosa cell differentiation in vitro. Biol Reprod. 1999;61(2):482–92 [Comparative Study Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  102. 102.
    Eppig JJ, Hosoe M, O’Brien MJ, Pendola FM, Requena A, Watanabe S. Conditions that affect acquisition of developmental competence by mouse oocytes in vitro: FSH, insulin, glucose and ascorbic acid. Mol Cell Endocrinol. 2000;163(1–2):109–16 [In Vitro Research Support, U.S. Gov’t, P.H.S. Review].PubMedCrossRefGoogle Scholar
  103. 103.
    Sánchez F, Adriaenssens T, Romero S, Smitz J. Different follicle-stimulating hormone exposure regimens during antral follicle growth alter gene expression in the cumulus-oocyte complex in mice. Biol Reprod. 2010;83(4):514–24 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  104. 104.
    Sanchez F, Romero S, Smitz J. Oocyte and cumulus cell transcripts from cultured mouse follicles are induced to deviate from normal in vivo condition by combinations of insulin, follicle-stimulating hormone, and human chorionic gonadotropin. Biol Reprod. 2011;85:565–74.PubMedCrossRefGoogle Scholar
  105. 105.
    Lenie S, Cortvrindt R, Adriaenssens T, Smitz J. A reproducible two-step culture system for isolated primary mouse ovarian follicles as single functional units. Biol Reprod. 2004;71(5):1730–8 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  106. 106.
    Muruvi W, Picton HM, Rodway RG, Joyce IM. In vitro growth and differentiation of primary follicles isolated from cryopreserved sheep ovarian tissue. Anim Reprod Sci. 2009;112(1–2):36–50 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  107. 107.
    Cortvrindt R, Smitz J, Van Steirteghem AC. In-vitro maturation, fertilization and embryo development of immature oocytes from early preantral follicles from prepuberal mice in a simplified culture system. Hum Reprod. 1996;11(12):2656–66 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  108. 108.
    Cortvrindt RG, Smitz JE. Follicle culture in reproductive toxicology: a tool for in-vitro testing of ­ovarian function? Hum Reprod Update. 2002;8(3):243–54 [Research Support, Non-U.S. Gov’t Review].PubMedCrossRefGoogle Scholar
  109. 109.
    Nayudu PL, Osborn SM. Factors influencing the rate of preantral and antral growth of mouse ovarian follicles in vitro. J Reprod Fertil. 1992;95(2):349–62 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  110. 110.
    Murray AA, Gosden RG, Allison V, Spears N. Effect of androgens on the development of mouse follicles growing in vitro. J Reprod Fertil. 1998;113(1):27–33 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  111. 111.
    Rose UM, Hanssen RG, Kloosterboer HJ. Development and characterization of an in vitro ovulation model using mouse ovarian follicles. Biol Reprod. 1999;61(2):503–11.PubMedCrossRefGoogle Scholar
  112. 112.
    Murray AA, Swales AK, Smith RE, Molinek MD, Hillier SG, Spears N. Follicular growth and oocyte competence in the in vitro cultured mouse follicle: effects of gonadotrophins and steroids. Mol Hum Reprod. 2008;14(2):75–83 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  113. 113.
    Boland NI, Humpherson PG, Leese HJ, Gosden RG. Pattern of lactate production and steroidogenesis during growth and maturation of mouse ovarian follicles in vitro. Biol Reprod. 1993;48(4):798–806 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  114. 114.
    Spears N, Boland NI, Murray AA, Gosden RG. Mouse oocytes derived from in vitro grown primary ovarian follicles are fertile. Hum Reprod. 1994;9(3):527–32 [Research Support, Non-U.S. Gov’t].PubMedGoogle Scholar
  115. 115.
    Johnson LD, Albertini DF, McGinnis LK, Biggers JD. Chromatin organization, meiotic status and meiotic competence acquisition in mouse oocytes from cultured ovarian follicles. J Reprod Fertil. 1995;104(2):277–84 [Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  116. 116.
    Carroll J, Whittingham DG, Wood MJ. Effect of dibutyryl cyclic adenosine monophosphate on granulosa cell proliferation, oocyte growth and meiotic maturation in isolated mouse primary ovarian follicles cultured in collagen gels. J Reprod Fertil. 1991;92(1):197–207 [Comparative Study Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  117. 117.
    Hulshof SC, Figueiredo JR, Beckers JF, Bevers MM, van der Donk JA, van den Hurk R. Effects of fetal bovine serum, FSH and 17beta-estradiol on the culture of bovine preantral follicles. Theriogenology. 1995;44(2):217–26.PubMedCrossRefGoogle Scholar
  118. 118.
    Sharma GT, Dubey PK, Meur SK. Survival and developmental competence of buffalo preantral follicles using three-dimensional collagen gel culture system. Anim Reprod Sci. 2009;114(1–3):115–24 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  119. 119.
    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 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  120. 120.
    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 [In Vitro Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  121. 121.
    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 [In Vitro Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  122. 122.
    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. 2009;24(10):2531–40 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  123. 123.
    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 [Evaluation Studies Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  124. 124.
    West-Farrell ER, Xu M, Gomberg MA, Chow YH, Woodruff TK, Shea LD. The mouse follicle microenvironment regulates antrum formation and steroid production: alterations in gene expression profiles. Biol Reprod. 2009;80(3):432–9 [Research Support, N.I.H., Extramural].PubMedCrossRefGoogle Scholar
  125. 125.
    Shikanov A, Xu M, Woodruff TK, Shea LD. A method for ovarian follicle encapsulation and culture in a proteolytically degradable 3 dimensional system. J Vis Exp. 2011;2011 [Research Support, N.I.H., Extramural Video-Audio Media].Google Scholar
  126. 126.
    Fehrenbach A, Nusse N, Nayudu PL. Patterns of growth, oestradiol and progesterone released by in vitro cultured mouse ovarian follicles indicate consecutive selective events during follicle development. J Reprod Fertil. 1998;113(2):287–97 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  127. 127.
    Vitt UA, Kloosterboer HJ, Rose UM, Mulders JW, Kiesel PS, Bete S, et al. Isoforms of human recombinant follicle-stimulating hormone: comparison of effects on murine follicle development in vitro. Biol Reprod. 1998;59(4):854–61 [Comparative Study In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  128. 128.
    Sánchez F, Romero S, Albuz FK, Smitz J. In vitro follicle growth under non-attachment conditions and decreased FSH levels reduces Lhcgr expression in cumulus cells and promotes oocyte developmental competence. J Assist Reprod Genet. 2012;29(2):141–52.PubMedCrossRefGoogle Scholar
  129. 129.
    Downs SM, Mastropolo AM. Culture conditions affect meiotic regulation in cumulus cell-enclosed mouse oocytes. Mol Reprod Dev. 1997;46(4):551–66 [Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  130. 130.
    Smitz J, Cortvrindt R, Hu Y. Epidermal growth factor combined with recombinant human chorionic gonadotrophin improves meiotic progression in mouse follicle-enclosed oocyte culture. Hum Reprod. 1998;13(3):664–9 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  131. 131.
    Smitz J, Cortvrindt R, Hu Y, Vanderstichele H. Effects of recombinant activin A on in vitro culture of mouse preantral follicles. Mol Reprod Dev. 1998;50(3):294–304 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  132. 132.
    Vitt UA, Nayudu PL, Rose UM, Kloosterboer HJ. Embryonic development after follicle culture is influenced by follicle-stimulating hormone isoelectric point range. Biol Reprod. 2001;65(5):1542–7 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  133. 133.
    Bishonga C, Takahashi Y, Katagiri S, Nagano M, Ishikawa A. In vitro growth of mouse ovarian preantral follicles and the capacity of their oocytes to develop to the blastocyst stage. J Vet Med Sci. 2001;63(6):619–24 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  134. 134.
    Mousset-Simeon N, Jouannet P, Le Cointre L, Coussieu C, Poirot C. Comparison of three in vitro culture systems for maturation of early preantral mouse ovarian follicles. Zygote. 2005;13(2):167–75 [Comparative Study Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  135. 135.
    Cortvrindt RG, Hu Y, Liu J, Smitz JE. Timed analysis of the nuclear maturation of oocytes in early preantral mouse follicle culture supplemented with recombinant gonadotropin. Fertil Steril. 1998;70(6):1114–25 [Clinical Trial Randomized Controlled Trial Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  136. 136.
    Zuccotti M, Merico V, Redi CA, Bellazzi R, Adjaye J, Garagna S. Role of Oct-4 during acquisition of developmental competence in mouse oocyte. Reprod Biomed Online. 2009;19 Suppl 3:57–62 [Research Support, Non-U.S. Gov’t Review].PubMedCrossRefGoogle Scholar
  137. 137.
    De La Fuente R, Viveiros MM, Burns KH, Adashi EY, Matzuk MM, Eppig JJ. Major chromatin remodeling in the germinal vesicle (GV) of mammalian oocytes is dispensable for global transcriptional silencing but required for centromeric heterochromatin function. Dev Biol. 2004;275(2):447–58 [Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].CrossRefGoogle Scholar
  138. 138.
    De La Fuente R, Eppig JJ. Transcriptional activity of the mouse oocyte genome: companion granulosa cells modulate transcription and chromatin remodeling. Dev Biol. 2001;229(1):224–36 [Research Support, U.S. Gov’t, P.H.S.].CrossRefGoogle Scholar
  139. 139.
    Segers I, Adriaenssens T, Ozturk E, Smitz J. Acquisition and loss of oocyte meiotic and developmental competence during in vitro antral follicle growth in mouse. Fertil Steril. 2010;93(8):2695–700 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  140. 140.
    Abir R, Franks S, Mobberley MA, Moore PA, Margara RA, Winston RM. Mechanical isolation and in vitro growth of preantral and small antral human follicles. Fertil Steril. 1997;68(4):682–8 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  141. 141.
    Cortvrindt R, Smitz J, Van Steirteghem AC. Assessment of the need for follicle stimulating hormone in early preantral mouse follicle culture in vitro. Hum Reprod. 1997;12(4):759–68 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  142. 142.
    Adriaens I, Cortvrindt R, Smitz J. Differential FSH exposure in preantral follicle culture has marked effects on folliculogenesis and oocyte developmental competence. Hum Reprod. 2004;19(2):398–408 [Comparative Study Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  143. 143.
    Cortvrindt R, Hu Y, Smitz J. Recombinant luteinizing hormone as a survival and differentiation factor increases oocyte maturation in recombinant follicle stimulating hormone-supplemented mouse preantral follicle culture. Hum Reprod. 1998;13(5):1292–302 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  144. 144.
    Schroeder AC, Schultz RM, Kopf GS, Taylor FR, Becker RB, Eppig JJ. Fetuin inhibits zona pellucida hardening and conversion of ZP2 to ZP2f during spontaneous mouse oocyte maturation in vitro in the absence of serum. Biol Reprod. 1990;43(5):891–7 [Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  145. 145.
    Mao J, Smith MF, Rucker EB, Wu GM, McCauley TC, Cantley TC, et al. Effect of epidermal growth factor and insulin-like growth factor I on porcine preantral follicular growth, antrum formation, and stimulation of granulosal cell proliferation and suppression of apoptosis in vitro. J Anim Sci. 2004;82(7):1967–75 [Research Support, Non-U.S. Gov’t].PubMedGoogle Scholar
  146. 146.
    Demeestere I, Gervy C, Centner J, Devreker F, Englert Y, Delbaere A. Effect of insulin-like growth factor-I during preantral follicular culture on steroidogenesis, in vitro oocyte maturation, and embryo development in mice. Biol Reprod. 2004;70(6):1664–9 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  147. 147.
    Hu YC, Wang PH, Yeh S, Wang RS, Xie C, Xu Q, et al. Subfertility and defective folliculogenesis in female mice lacking androgen receptor. Proc Natl Acad Sci USA. 2004;101(31):11209–14 [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S.].PubMedCrossRefGoogle Scholar
  148. 148.
    Shiina H, Matsumoto T, Sato T, Igarashi K, Miyamoto J, Takemasa S, et al. Premature ovarian failure in androgen receptor-deficient mice. Proc Natl Acad Sci USA. 2006;103(1):224–9 [Comparative Study Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  149. 149.
    Spears N, Murray AA, Allison V, Boland NI, Gosden RG. Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro. J Reprod Fertil. 1998;113(1):19–26 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  150. 150.
    Vendola KA, Zhou J, Adesanya OO, Weil SJ, Bondy CA. Androgens stimulate early stages of follicular growth in the primate ovary. J Clin Invest. 1998;101(12):2622–9.PubMedCrossRefGoogle Scholar
  151. 151.
    Weil S, Vendola K, Zhou J, Bondy CA. Androgen and follicle-stimulating hormone interactions in primate ovarian follicle development. J Clin Endocrinol Metab. 1999;84(8):2951–6.PubMedCrossRefGoogle Scholar
  152. 152.
    Yang MY, Fortune JE. Testosterone stimulates the primary to secondary follicle transition in bovine follicles in vitro. Biol Reprod. 2006;75(6):924–32 [In Vitro Research Support, U.S. Gov’t, Non-P.H.S.].PubMedCrossRefGoogle Scholar
  153. 153.
    Lenie S, Smitz J. Functional AR signaling is evident in an in vitro mouse follicle culture bioassay that encompasses most stages of folliculogenesis. Biol Reprod. 2009;80(4):685–95 [Evaluation Studies Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  154. 154.
    Andersen CY, Ziebe S. Serum levels of free androstenedione, testosterone and oestradiol are lower in the follicular phase of conceptional than of non-conceptional cycles after ovarian stimulation with a gonadotrophin-releasing hormone agonist protocol. Hum Reprod. 1992;7(10):1365–70 [Comparative Study Research Support, Non-U.S. Gov’t].PubMedGoogle Scholar
  155. 155.
    Tetsuka M, Hillier SG. Differential regulation of aromatase and androgen receptor in granulosa cells. J Steroid Biochem Mol Biol. 1997;61(3–6):233–9 [Research Support, Non-U.S. Gov’t Review].PubMedCrossRefGoogle Scholar
  156. 156.
    Couse JF, Yates MM, Deroo BJ, Korach KS. Estrogen receptor-beta is critical to granulosa cell differentiation and the ovulatory response to gonadotropins. Endocrinology. 2005;146(8):3247–62.PubMedCrossRefGoogle Scholar
  157. 157.
    Romero S, Smitz J. Exposing cultured mouse ovarian follicles under increased gonadotropin tonus to aromatizable androgens influences the steroid balance and reduces oocyte meiotic capacity. Endocrine. 2010;38(2):243–53.PubMedCrossRefGoogle Scholar
  158. 158.
    Park JY, Su YQ, Ariga M, Law E, Jin SL, Conti M. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science. 2004;303(5658):682–4.PubMedCrossRefGoogle Scholar
  159. 159.
    Ashkenazi H, Cao X, Motola S, Popliker M, Conti M, Tsafriri A. Epidermal growth factor family members: endogenous mediators of the ovulatory response. Endocrinology. 2005;146(1):77–84.PubMedCrossRefGoogle Scholar
  160. 160.
    Yamashita Y, Kawashima I, Yanai Y, Nishibori M, Richards JS, Shimada M. Hormone-induced expression of tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloprotease-17 impacts porcine cumulus cell oocyte complex expansion and meiotic maturation via ligand activation of the epidermal growth factor receptor. Endocrinology. 2007;148(12):6164–75 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  161. 161.
    Fru KN, Cherian-Shaw M, Puttabyatappa M, VandeVoort CA, Chaffin CL. Regulation of granulosa cell proliferation and EGF-like ligands during the periovulatory interval in monkeys. Hum Reprod. 2007;22(5):1247–52 [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  162. 162.
    Freimann S, Ben-Ami I, Dantes A, Ron-El R, Amsterdam A. EGF-like factor epiregulin and amphiregulin expression is regulated by gonadotropins/cAMP in human ovarian follicular cells. Biochem Biophys Res Commun. 2004;324(2):829–34 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  163. 163.
    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.PubMedCrossRefGoogle Scholar
  164. 164.
    Romero S, Sanchez F, Adriaenssens T, Smitz J. Mouse cumulus-oocyte complexes from in vitro-cultured preantral follicles suggest an anti-luteinizing role for the EGF cascade in the cumulus cells. Biol Reprod. 2011;84(6):1164–70 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  165. 165.
    Nogueira D, Staessen C, Van de Velde H, Van Steirteghem A. Nuclear status and cytogenetics of embryos derived from in vitro-matured oocytes. Fertil Steril. 2000;74(2):295–8 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  166. 166.
    Fadini R, Comi R, Mignini Renzini M, Coticchio G, Crippa M, De Ponti E, et al. Anti-mullerian hormone as a predictive marker for the selection of women for oocyte in vitro maturation treatment. J Assist Reprod Genet. 2011;28(6):501–8.PubMedCrossRefGoogle Scholar
  167. 167.
    Smitz JE, Thompson JG, Gilchrist RB. The promise of in vitro maturation in assisted reproduction and fertility preservation. Semin Reprod Med. 2011;29(1):24–37 [Research Support, Non-U.S. Gov’t Review].PubMedCrossRefGoogle Scholar
  168. 168.
    Nogueira D, Cortvrindt R, De Matos DG, Vanhoutte L, Smitz J. Effect of phosphodiesterase type 3 inhibitor on developmental competence of immature mouse oocytes in vitro. Biol Reprod. 2003;69(6):2045–52 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  169. 169.
    Vanhoutte L, Nogueira D, Gerris J, Dhont M, De Sutter P. Effect of temporary nuclear arrest by phosphodiesterase 3-inhibitor on morphological and functional aspects of in vitro matured mouse oocytes. Mol Reprod Dev. 2008;75(6):1021–30 [In Vitro Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  170. 170.
    Thomas RE, Armstrong DT, Gilchrist RB. Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation. Dev Biol. 2002;244(2):215–25 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  171. 171.
    Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod. 2010;25(12):2999–3011 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  172. 172.
    Nogueira D, Albano C, Adriaenssens T, Cortvrindt R, Bourgain C, Devroey P, et al. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. Biol Reprod. 2003;69(3):1042–52 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  173. 173.
    Nogueira D, Ron-El R, Friedler S, Schachter M, Raziel A, Cortvrindt R, et al. Meiotic arrest in vitro by phosphodiesterase 3-inhibitor enhances maturation capacity of human oocytes and allows subsequent embryonic development. Biol Reprod. 2006;74(1):177–84 [In Vitro].PubMedCrossRefGoogle Scholar
  174. 174.
    Vanhoutte L, De Sutter P, Nogueira D, Gerris J, Dhont M, Van der Elst J. Nuclear and cytoplasmic maturation of in vitro matured human oocytes after temporary nuclear arrest by phosphodiesterase 3-inhibitor. Hum Reprod. 2007;22(5):1239–46 [Evaluation Studies Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar
  175. 175.
    Shu YM, Zeng HT, Ren Z, Zhuang GL, Liang XY, Shen HW, et al. Effects of cilostamide and forskolin on the meiotic resumption and embryonic development of immature human oocytes. Hum Reprod. 2008;23(3):504–13 [Research Support, Non-U.S. Gov’t].PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Sergio Romero
    • 1
  • Sandra Sanfilippo
    • 2
  • Johan Smitz
    • 1
    • 3
    Email author
  1. 1.Follicle Biology LaboratoryUZ Brussel – Vrije Universiteit BrusselBrusselsBelgium
  2. 2.Laboratoire de biologie du développement et de la reproductionE.A. 975, Université Clermont 1, UFR MédecineClermont-Ferrand, Cedex 1France
  3. 3.Laboratory of Hormonology and Tumormarkers, Department of Clinical Chemistry/AnatomopathologyUniversity Hospital Free University Brussels (UZ Brussel)BrusselsBelgium

Personalised recommendations