Skip to main content
Log in

Growth hormone and in vitro maturation of rhesus macaque oocytes and subsequent embryo development

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

Abstract

Purpose

The objective of this study was to use a nonhuman primate model to examine the effects of growth hormone (GH) on oocyte in vitro maturation (IVM).

Methods

Immunocytochemistry confirmed the presence of GH receptors in rhesus cumulus oocyte complexes and the cytoplasm of embryonic blastomeres. Recombinant human GH (r-hGH) was added to IVM medium and cumulus expansion, nuclear maturation, cytoplasmic maturation and embryo development were analyzed.

Results

Cumulus expansion was highest in the presence of 1 and 10 ng/ml r-hGH. The addition of r-hGH during IVM increased the percentage of embryos progressing to at least the 9–16 cell stage. In a separate study, 100 ng/ml r-hGH was supplemented to IVM and embryo culture medium and no effect was observed.

Conclusions

The presence of GH receptors along with increased cumulus expansion and embryos progressing to the 9–16 cell stage supports the hypothesis that r-hGH may be involved in oocyte maturation.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Dekel N, Lawrence TS, Gilula NB, Beers WH. Modulation of cell-to-cell communication in the cumulus-oocyte complex and the regulation of oocyte maturation by LH. Dev Biol 1981;86:356–62.

    Article  PubMed  CAS  Google Scholar 

  2. Tanghe S, Van Soom A, Nauwynck H, Coryn M, de Kruif A. Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol Reprod Dev 2002;61:414–24.

    Article  PubMed  CAS  Google Scholar 

  3. Chian RC, Lim JH, Tan SL. State of the art in in-vitro oocyte maturation. Curr Opin Obstet Gynecol 2004;16:211–9.

    Article  PubMed  Google Scholar 

  4. Cha KY, Chian RC. Maturation in vitro of immature human oocytes for clinical use. Hum Reprod Updat 1998;4:103–20.

    Article  CAS  Google Scholar 

  5. Schramm RD, Bavister BD. A macaque model for studying mechanisms controlling oocyte development and maturation in human and non-human primates. Hum Reprod 1999;14:2544–55.

    Article  PubMed  CAS  Google Scholar 

  6. Bergh PA, Navot D. Ovarian hyperstimulation syndrome: a review of pathophysiology. J Assist Reprod Genet 1992;9:429–38.

    Article  PubMed  CAS  Google Scholar 

  7. Apa R, Lanzone A, Miceli F, Mastrandrea M, Caruso A, Mancuso S, et al. Growth hormone induces in vitro maturation of follicle- and cumulus-enclosed rat oocytes. Mol Cell Endocrinol 1994;106:207–12.

    Article  PubMed  CAS  Google Scholar 

  8. Izadyar F, Van Tol HT, Colenbrander B, Bevers MM. Stimulatory effect of growth hormone on in vitro maturation of bovine oocytes is exerted through cumulus cells and not mediated by IGF-I. Mol Reprod Dev 1997;47:175–80.

    Article  PubMed  CAS  Google Scholar 

  9. Marchal R, Caillaud M, Martoriati A, Gerard N, Mermillod P, Goudet G. Effect of growth hormone (GH) on in vitro nuclear and cytoplasmic oocyte maturation, cumulus expansion, hyaluronan synthases, and connexins 32 and 43 expression, and GH receptor messenger RNA expression in equine and porcine species. Biol Reprod 2003;69:1013–22.

    Article  PubMed  CAS  Google Scholar 

  10. Yoshimura Y, Nakamura Y, Koyama N, Iwashita M, Adachi T, Takeda Y. Effects of growth hormone on follicle growth, oocyte maturation, and ovarian steroidogenesis. Fertil Steril 1993;59:917–23.

    PubMed  CAS  Google Scholar 

  11. Herrington J, Carter-Su C. Signaling pathways activated by the growth hormone receptor. Trends Endocrinol Metab 2001;12:252–7.

    Article  PubMed  CAS  Google Scholar 

  12. Hull KL, Harvey S. Growth hormone: roles in female reproduction. J Endocrinol 2001;168:1–23.

    Article  PubMed  CAS  Google Scholar 

  13. Mason HD, Martikainen H, Beard RW, Anyaoku V, Franks S. Direct gonadotrophic effect of growth hormone on oestradiol production by human granulosa cells in vitro. J Endocrinol 1990;126:R1–4.

    PubMed  CAS  Google Scholar 

  14. Menezo YJ, el Mouatassim S, Chavrier M, Servy EJ, Nicolet B. Human oocytes and preimplantation embryos express mRNA for growth hormone receptor. Zygote 2003;11:293–7.

    Article  PubMed  CAS  Google Scholar 

  15. Sharara FI, Nieman LK. Identification and cellular localization of growth hormone receptor gene expression in the human ovary. J Clin Endocrinol Metab 1994;79:670–2.

    Article  PubMed  CAS  Google Scholar 

  16. Hassan HA, Azab H, Rahman AA, Nafee TM. Effects of growth hormone on in vitro maturation of germinal vesicle of human oocytes retrieved from small antral follicles. J Assist Reprod Genet 2001;18:417–20.

    Article  PubMed  CAS  Google Scholar 

  17. Mendoza C, Ruiz-Requena E, Ortega E, Cremades N, Martinez F, Bernabeu R, et al. Follicular fluid markers of oocyte developmental potential. Hum Reprod 2002;17:1017–22.

    Article  PubMed  CAS  Google Scholar 

  18. Fukaya T, Yamanaka T, Terada Y, Murakami T, Yajima A. Growth hormone improves mouse embryo development in vitro, and the effect is neutralized by growth hormone receptor antibody. Tohoku J Exp Med 1998;184:113–22.

    Article  PubMed  CAS  Google Scholar 

  19. Izadyar F, Van Tol HT, Hage WG, Bevers MM. Preimplantation bovine embryos express mRNA of growth hormone receptor and respond to growth hormone addition during in vitro development. Mol Reprod Dev 2000;57:247–55.

    Article  PubMed  CAS  Google Scholar 

  20. Kidson A, Rubio-Pomar FJ, Van Knegsel A, Van Tol HT, Hazeleger W, Ducro-Steverink DW, et al. Quality of porcine blastocysts produced in vitro in the presence or absence of GH. Reproduction 2004;127:165–77.

    Article  PubMed  CAS  Google Scholar 

  21. Markham KE, Kaye PL. Growth hormone, insulin-like growth factor I and cell proliferation in the mouse blastocyst. Reproduction 2003;125:327–36.

    Article  PubMed  CAS  Google Scholar 

  22. Moreira F, Paula-Lopes FF, Hansen PJ, Badinga L, Thatcher WW. Effects of growth hormone and insulin-like growth factor-I on development of in vitro derived bovine embryos. Theriogenology 2002;57:895–907.

    Article  PubMed  CAS  Google Scholar 

  23. Ellinwood WE, Resko JA. Sex differences in biologically active and immunoreactive gonadotropins in the fetal circulation of rhesus monkeys. Endocrinology 1980;107:902–7.

    Article  PubMed  CAS  Google Scholar 

  24. Molskness TA, Woodruff TK, Hess DL, Dahl KD, Stouffer RL. Recombinant human inhibin-A administered early in the menstrual cycle alters concurrent pituitary and follicular, plus subsequent luteal, function in rhesus monkeys. J Clin Endocrinol Metab 1996;81:4002–6.

    Article  PubMed  CAS  Google Scholar 

  25. Young KA, Chaffin CL, Molskness TA, Stouffer RL. Controlled ovulation of the dominant follicle: a critical role for LH in the late follicular phase of the menstrual cycle. Hum Reprod 2003;18:2257–63.

    Article  PubMed  CAS  Google Scholar 

  26. Vandevoort CA, Baughman WL, Stouffer RL. Comparison of different regimens of human gonadotropins for superovulation of rhesus monkeys: ovulatory response and subsequent luteal function. J In Vitro Fert Embryo Transf 1989;6:85–91.

    Article  PubMed  CAS  Google Scholar 

  27. VandeVoort CA, Leibo SP, Tarantal AF. Improved collection and developmental competence of immature macaque oocytes. Theriogenology 2003;59:699–707.

    Article  PubMed  CAS  Google Scholar 

  28. Boatman DE. In vitro growth of non-human primate pre- and peri- implantation embryos. In: Bavister BD, editor. The mammalian preimplantation embryo: regulation of growth and differentiation in vitro. New York: Plenum Press; 1987. p. 273–308.

    Google Scholar 

  29. Allworth AE, Albertini DF. Meiotic maturation in cultured bovine oocytes is accompanied by remodeling of the cumulus cell cytoskeleton. Dev Biol 1993;158:101–12.

    Article  PubMed  CAS  Google Scholar 

  30. McKiernan SH, Bavister BD. Culture of one-cell hamster embryos with water soluble vitamins: pantothenate stimulates blastocyst production. Hum Reprod 2000;15:157–64.

    Article  PubMed  CAS  Google Scholar 

  31. Liu JC, Makova KD, Adkins RM, Gibson S, Li WH. Episodic evolution of growth hormone in primates and emergence of the species specificity of human growth hormone receptor. Mol Biol Evol 2001;18:945–53.

    PubMed  CAS  Google Scholar 

  32. Martini JF, Pezet A, Guezennec CY, Edery M, Postel-Vinay MC, Kelly PA. Monkey growth hormone (GH) receptor gene expression. Evidence for two mechanisms for the generation of the GH binding protein. J Biol Chem 1997;272:18951–8.

    Article  PubMed  CAS  Google Scholar 

  33. Briggs D, Miller D, Gosden R. Molecular biology of female gametogenesis. In: Fauser B, Rutherford A, Strauss J, editors. Molecular biology in reproductive medicine. New York: The Parthenon Publishing Group; 1999. p. 254–6.

    Google Scholar 

  34. Schramm RD, Bavister BD. Follicle-stimulating hormone priming of rhesus monkeys enhances meiotic and developmental competence of oocytes matured in vitro. Biol Reprod 1994;51:904–12.

    Article  PubMed  CAS  Google Scholar 

  35. Sarason RL, VandeVoort CA, Mader DR, Overstreet JW. The use of nonmetal electrodes in electroejaculation of restrained but unanesthetized macaques. J Med Primatol 1991;20:122–5.

    PubMed  CAS  Google Scholar 

  36. Tamura M, Sasano H, Suzuki T, Fukaya T, Watanabe T, Aoki H, et al. Immunohistochemical localization of growth hormone receptor in cyclic human ovaries. Hum Reprod 1994;9:2259–62.

    PubMed  CAS  Google Scholar 

  37. Kiapekou E, Loutradis D, Drakakis P, Zapanti E, Mastorakos G, Antsaklis A. Effects of GH and IGF-I on the in vitro maturation of mouse oocytes. Hormones (Athens) 2005;4:155–60.

    Google Scholar 

  38. Kolle S, Sinowatz F, Boie G, Lincoln D. Developmental changes in the expression of the growth hormone receptor messenger ribonucleic acid and protein in the bovine ovary. Biol Reprod 1998;59:836–42.

    Article  PubMed  CAS  Google Scholar 

  39. Zhu T, Goh EL, Graichen R, Ling L, Lobie PE. Signal transduction via the growth hormone receptor. Cell Signal 2001;13:599–616.

    Article  PubMed  CAS  Google Scholar 

  40. Chen L, Russell PT, Larsen WJ. Functional significance of cumulus expansion in the mouse: roles for the preovulatory synthesis of hyaluronic acid within the cumulus mass. Mol Reprod Dev 1993;34:87–93.

    Article  PubMed  CAS  Google Scholar 

  41. Moor R, Osborn J, Crosby I. Cell interactions and ooctye regulation in mammals. In: Rolland R, Van Hall E, Hillier S, McNatty K, editors. Follicular maturation and ovulation. Oxford: Excerpta Medica; 1981. p. 249–64.

    Google Scholar 

  42. Ball GD, Leibfried ML, Lenz RW, Ax RL, Bavister BD, First NL. Factors affecting successful in vitro fertilization of bovine follicular oocytes. Biol Reprod 1983;28:717–25.

    Article  PubMed  CAS  Google Scholar 

  43. Zhuo L, Kimata K. Cumulus oophorus extracellular matrix: its construction and regulation. Cell Struct Funct 2001;26:189–96.

    Article  PubMed  CAS  Google Scholar 

  44. Qian Y, Shi WQ, Ding JT, Sha JH, Fan BQ. Predictive value of the area of expanded cumulus mass on development of porcine oocytes matured and fertilized in vitro. J Reprod Dev 2003;49:167–74.

    Article  PubMed  Google Scholar 

  45. Rose-Hellekant TA, Libersky-Williamson EA, Bavister BD. Energy substrates and amino acids provided during in vitro maturation of bovine oocytes alter acquisition of developmental competence. Zygote 1998;6:285–94.

    Article  PubMed  CAS  Google Scholar 

  46. Foote RH. In vitro fertilization and embryo transfer in domestic animals: applications in animals and implications for humans. J In Vitro Fert Embryo Transf 1987;4:73–88.

    Article  PubMed  CAS  Google Scholar 

  47. Laufer N, Tarlatzis BC, Naftolin F. In vitro fertilization: state of the art. Semin Reprod Endocrinol 1984;2:197–219.

    Article  Google Scholar 

  48. Kolle S, Stojkovic M, Boie G, Wolf E, Sinowatz F. Growth hormone-related effects on apoptosis, mitosis, and expression of connexin 43 in bovine in vitro maturation cumulus-oocyte complexes. Biol Reprod 2003;68:1584–9.

    Article  PubMed  CAS  Google Scholar 

  49. Izadyar F, Colenbrander B, Bevers MM. In vitro maturation of bovine oocytes in the presence of growth hormone accelerates nuclear maturation and promotes subsequent embryonic development. Mol Reprod Dev 1996;45:372–7.

    Article  PubMed  CAS  Google Scholar 

  50. Thibault C. Hammond memorial lecture. Are follicular maturation and oocyte maturation independent processes? J Reprod Fertil 1977;51:1–15.

    Article  PubMed  CAS  Google Scholar 

  51. Thibault C, Gerard M, Menezo Y. Preovulatory and ovulatory mechanisms in oocyte maturation. J Reprod Fertil 1975;45:605–10.

    Article  PubMed  CAS  Google Scholar 

  52. Cunningham BC, Ultsch M, De Vos AM, Mulkerrin MG, Clauser KR, Wells JA. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science 1991;254:821–5.

    Article  PubMed  CAS  Google Scholar 

  53. Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science 1992;256:1677–80.

    Article  PubMed  CAS  Google Scholar 

  54. Gent J, Van Den Eijnden M, Van Kerkhof P, Strous GJ. Dimerization and signal transduction of the growth hormone receptor. Mol Endocrinol 2003;17:967–75.

    Article  PubMed  CAS  Google Scholar 

  55. Gent J, van Kerkhof P, Roza M, Bu G, Strous GJ. Ligand-independent growth hormone receptor dimerization occurs in the endoplasmic reticulum and is required for ubiquitin system-dependent endocytosis. Proc Natl Acad Sci U S A 2002;99:9858–63.

    Article  PubMed  CAS  Google Scholar 

  56. Izadyar F, Hage WJ, Colenbrander B, Bevers MM. The promotory effect of growth hormone on the developmental competence of in vitro matured bovine oocytes is due to improved cytoplasmic maturation. Mol Reprod Dev 1998;49:444–53.

    Article  PubMed  CAS  Google Scholar 

  57. Artley JK, Braude PR, Johnson MH. Gene activity and cleavage arrest in human pre-embryos. Hum Reprod 1992;7:1014–21.

    PubMed  CAS  Google Scholar 

  58. Schramm RD, Bavister BD. Onset of nucleolar and extranucleolar transcription and expression of fibrillarin in macaque embryos developing in vitro. Biol Reprod 1999;60:721–8.

    Article  PubMed  CAS  Google Scholar 

  59. Tesarik J. Gene activation in the human embryo developing in vitro. In: Feichtinger W, Kemeter P, editors. Future aspects in human in vitro fertilization. Berlin: Springer-Verlag; 1987. p. 251–61.

    Google Scholar 

  60. Tesarik J, Kopecny V, Plachot M, Mandelbaum J. Activation of nucleolar and extranucleolar RNA synthesis and changes in the ribosomal content of human embryos developing in vitro. J Reprod Fertil 1986;78:463–70.

    Article  PubMed  CAS  Google Scholar 

  61. Tesarik J, Kopecny V, Plachot M, Mandelbaum J. Early morphological signs of embryonic genome expression in human preimplantation development as revealed by quantitative electron microscopy. Dev Biol 1988;128:15–20.

    Article  PubMed  CAS  Google Scholar 

  62. Tesarik J, Kopecny V, Plachot M, Mandelbaum J, Da Lage C, Flechon JE. Nucleologenesis in the human embryo developing in vitro: ultrastructural and autoradiographic analysis. Dev Biol 1986;115:193–203.

    Article  PubMed  CAS  Google Scholar 

  63. Weston AM, Wolf DP. Timing of the maternal to embryonic transition in the rhesus monkey embryos. In Program of 27th annual meeting of the Society for the Study of Reproduction, Ann Arbor, MI, 1994, Abstract P297.

  64. Schramm RD, Paprocki AM, VandeVoort CA. Causes of developmental failure of in-vitro matured rhesus monkey oocytes: impairments in embryonic genome activation. Hum Reprod 2003;18:826–33.

    Article  PubMed  CAS  Google Scholar 

  65. Enders AC, Boatman D, Morgan P, Bavister BD. Differentiation of blastocysts derived from in vitro-fertilized rhesus monkey ova. Biol Reprod 1989;41:715–27.

    Article  PubMed  CAS  Google Scholar 

  66. Enders AC, Schlafke S. Differentiation of the blastocyst of the rhesus monkey. Am J Anat 1981;162:1–21.

    Article  PubMed  CAS  Google Scholar 

  67. Lane M, Gardner DK. Differential regulation of mouse embryo development and viability by amino acids. J Reprod Fertil 1997;109:153–64.

    Article  PubMed  CAS  Google Scholar 

  68. Richter KS, Harris DC, Daneshmand ST, Shapiro BS. Quantitative grading of a human blastocyst: optimal inner cell mass size and shape. Fertil Steril 2001;76:1157–67.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Dana Hill and Pei-Hsuan Hung for technical assistance. Part of this study was conducted in a facility constructed with support from Research Facilities Improvement Program Grants Numbers C06 RR17348-01 and C06 RR12088-01 from the National Center for Research Resources, National Institutes of Health.

Funding

National Institutes of Health (RR00169 and RR13439 to C.A.V.).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Catherine A. VandeVoort.

Additional information

Capsule

GH receptors are present on macaque COCs and r-hGH in IVM medium increased cumulus expansion and percentage of embryos progressing to the 9–16 cell stage.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nyholt de Prada, J.K., VandeVoort, C.A. Growth hormone and in vitro maturation of rhesus macaque oocytes and subsequent embryo development. J Assist Reprod Genet 25, 145–158 (2008). https://doi.org/10.1007/s10815-008-9208-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-008-9208-3

Keywords

Navigation