Skip to main content

The Biochemistry of Oocyte Maturation

  • Conference paper
The Future of the Oocyte

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 41))

Abstract

Oocyte maturation is a complex process that encompasses growth and differentiation of the oocyte, acquisition of meiotic competence, initiation and completion of nuclear maturation, and cytoplasmic changes related to fertilizability and post-fertilization developmental potential. The oocyte develops within a syncytial environment, being intimately coupled to the entire somatic compartment of the follicle via granulosaoocyte and granulosa—granulosa gap junctions (Larsen and Wert 1988). This condition provides an efficient delivery system through which small molecular weight nutritional and regulatory signals can reach the developing oocyte. As the oocyte grows, it continuously stockpiles macromolecules needed for later development, and near the end of its growth phase, the oocyte completes the biochemical changes required to achieve meiotic competence, a condition that supports the resumption of meiosis beyond prophase I. Once oocytes achieve meiotic competence, they are maintained in a prophase I-arrested, germinal vesicle stage until stimulated to resume maturation, either by the preovulatory gonadotropin surge or by follicular atresia. The former stimulus produces developmentally competent ova while the latter condition leads to degenerating oocytes trapped within anovulatory follicles. Meiotic progression beyond the germinal vesicle stage requires the activation of maturation, or M phase, promoting factor (MPF), a heterodimeric protein complex composed of a 34-kDa kinase and 45-kDa cyclin regulatory subunit. Control of the activity of MPF is an essential component of the system regulating both meiotic arrest and meiotic resumption, since this kinase is the driving force behind cell division. Following meiotic resumption (initially manifested by germinal vesicle breakdown), maturation proceeds through extrusion of the first polar body and formation of the second metaphase spindle (MII), where the oocyte arrests for a second time until activated by fertilization. For the purpose of this review, maturation will be defined as the process of meiosis reinitiation; the focus will be on regulation of the immature, germinal vesicle stage, with particular emphasis on how the oocyte is stimulated to resume meiotic maturation.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Aberdam E, Hanski E, Dekel N (1987) Maintenance of meiotic arrest in isolated rat oocytes by the invasive adenylate cyclase of Bordetella pertussis. Biol Reprod 36: 530–535

    Article  PubMed  CAS  Google Scholar 

  • Baltsen M (2001) Gonadotropin-induced accumulation of 4,4-dimethylsterols in mouse ovaries and its temporal relation to meiosis. Biol Reprod 65: 1743–1750

    Article  PubMed  CAS  Google Scholar 

  • Byskov AG, Andersen CY, Nordholm L, Thogersen H, Xia G, Wassman O, Andersen JV, Guddal E, Roed T (1995) Chemical structure of sterols that activate oocyte meiosis. Nature 374: 559–562

    Article  PubMed  CAS  Google Scholar 

  • Byskov AG, Andersen CY, Hossaini A, Guoliang X (1997) Cumulus cells of oocyte-cumulus complexes secrete a meiosis-activating substance when stimulated with FSH. Mol Reprod Dev 46: 296–305

    Article  PubMed  CAS  Google Scholar 

  • Cavilla JL, Kennedy CR, Baltsen M, Klentzeris LD, Byskov AG, Hartshorne GM (2001) Effects of meiosis activating sterol ( MAS) upon in vitro maturation and fertilization of human oocytes from stimulated and unstimulated ovaries. Hum Reprod 16: 547–555

    Google Scholar 

  • Chari S, Hillensjo T, Magnusson C, Sturm G, Daume E (1983) In vitro inhibition of rat oocyte meiosis by human follicular fluid fractions. Arch Gynecol 233: 155–164

    Article  PubMed  CAS  Google Scholar 

  • Coskun S, Lin YC (1994) Effects of transforming growth factors and activin-A on in vitro porcine oocyte maturation. Mol Reprod Dev 38: 153–159

    Article  PubMed  CAS  Google Scholar 

  • Coticchio G, Fleming S (1998) Inhibition of phosphoinositide metabolism or chelation of intracellular calcium blocks FSH-induced but not spontaneous meiotic resumption in mouse oocytes. Dev Biol 203: 201–209

    Article  PubMed  CAS  Google Scholar 

  • Dekel N, Beers WH (1978) Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins.

    Google Scholar 

  • Downs SM (1995b) The influence of Proc Natl Acad Sci USA 75: 4369–4373

    Google Scholar 

  • Dekel N, Beers WH (1980) Development of the rat oocyte: inhibition and induction of maturation in the presence or absence of the cumulus oophorus. Dev Biol 75: 274–254

    Article  Google Scholar 

  • Dekel N, Piontkewitz Y (1991) Induction of maturation in vitro of rat oocytes by interruption of communication in the cumulus-oocyte complex. Bull Assoc Anat 75: 51–54

    CAS  Google Scholar 

  • Dekel N, Galiani D, Sherizly I (1988) Dissociation between the inhibitory and the stimulatory action of cAMP on maturation of rat oocytes (1988) Mol Cell Endocrinol 56: 115–121

    Article  PubMed  CAS  Google Scholar 

  • Downs SM (1995a) Ovulation 2: control of the resumption of meiotic maturation in mammalian oocytes. In: Grudzinskas JG, Yovich JL (eds) Gametes — the oocyte. Cambridge University Press, Cambridge, pp 150–192

    Google Scholar 

  • glucose, cumulus cells, and metabolic coupling on ATP levels and meiotic control in the isolated mouse oocyte. Dev Biol 167:502–512

    Google Scholar 

  • Downs SM (1997) Involvement of purine nucleotide synthetic pathways in gonadotropin-induced meiotic maturation in mouse cumulus cell-enclosed oocytes. Mol Reprod Dev 46: 155–167

    Article  PubMed  CAS  Google Scholar 

  • Downs SM (2001) A gap-junction-mediated signal, rather than an external paracrine factor, predominates during meiotic induction in isolated mouse oocytes. Zygote 9: 71–82

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Eppig JJ (1984) Cyclic adenosine monophosphate and ovarian follicular fluid act synergistically to inhibit mouse oocyte maturation. Endocrinology 114: 418–427

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Hunzicker-Dunn M (1995) Differential regulation of oocyte maturation and cumulus expansion in the mouse oocyte-cumulus cell complex by site-selective analogs of cyclic adenosine monophosphate. Dev Biol 172: 72–85

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Mastropolo AM (1994) The participation of energy substrates in the control of meiotic maturation in murine oocytes. Dev Biol 162: 154–168

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Utecht AM (1999) Metabolism of radiolabeled glucose by mouse oocytes and oocyte-cumulus cell complexes. Biol Reprod 60: 1446–1452

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Coleman DL, Eppig JJ (1985) Hypoxanthine is the principal inhibitor of murine oocyte maturation in a low molecular weight fraction of porcine follicular fluid. Proc Natl Acad Sci USA 82: 454–458

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Coleman DL, Eppig JJ (1986) Maintenance of murine oocyte meiotic arrest: uptake and metabolism of hypoxanthine and adenosine by cumulus cell-enclosed and denuded oocytes. Dev Biol 117: 174–183

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Daniel SAJ, Eppig JJ (1988) Induction of maturation in cumulus cell-enclosed mouse oocytes by follicle-stimulating hormone and epidermal growth factor: evidence for a positive stimulus of somatic cell origin. J Exp Zool 245: 86–96

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Humpherson PG, Martin KL, Leese HJ (1996) Glucose utilization during gonadotropin-induced meiotic maturation in cumulus cell-enclosed mouse oocytes. Mol Reprod Dev 44: 121–131

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Humpherson PG, Leese HJ (1998) Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the pentose phosphate pathway. Biol Reprod 58: 1084–1094

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Cottom J, Hunzicker-Dunn M (2001a) Protein kinase C and mei-otic regulation in isolated mouse oocytes. Mol Reprod Dev 58: 101–115.

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Ruan B, Schroepfer GJ Jr (2001b) Meiosis-activating sterol and the maturation of isolated mouse oocytes. Biol Reprod 64: 80–89

    Article  PubMed  CAS  Google Scholar 

  • Downs SM, Hudson ER, Hardie DG (2002) A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Dev Biol 245: 200–212

    Article  PubMed  CAS  Google Scholar 

  • Eppig JJ, Downs SM (1988) Gonadotropin-induced murine oocyte maturation in vivo is not associated with decreased cyclic adenosine monophosphate in the oocyte-cumulus cell complex. Gamete Res 20: 125–131

    Article  PubMed  CAS  Google Scholar 

  • Eppig JJ, Ward-Bailey PF, Coleman DL (1985) Hypoxanthine and adenosine in murine ovarian follicular fluid: concentrations and activity in maintaining oocyte meiotic arrest. Biol Reprod 33: 1041–1049

    Article  PubMed  CAS  Google Scholar 

  • Eppig JJ, Wigglesworth K, Pendola F, Hirao Y (1997) Murine oocytes suppress expression of luteinizing hormone receptor messenger ribonucleic acid by granulosa cells. Biol Reprod 56: 976–984

    Article  PubMed  CAS  Google Scholar 

  • Fagbohun CF, Downs SM (1991) Metabolic coupling and ligand-stimulated meiotic maturation in the mouse oocyte-cumulus cell complex. Biol Reprod 45: 851–859

    Article  PubMed  CAS  Google Scholar 

  • Fagbohun CF, Downs SM (1992) Requirement for glucose in ligand-stimulated meiotic maturation of cumulus cell-enclosed mouse oocytes. J Reprod Fertil 96: 681–697

    Article  PubMed  CAS  Google Scholar 

  • Grondahl C, Ottesen JL, Lessl M, Faarup P, Murray A, Gronvald FC, HegeleHartung C, Ahnfelt-Ronne I (1998) Meiosis-activating sterol promotes resumption of meiosis in mouse oocytes cultured in vitro in contrast to related oxysterols. Biol Reprod 58: 1297–1302

    Article  PubMed  CAS  Google Scholar 

  • Grondahl C, Lessl M, Faerge I, Hegele-Hartung C, Wassermann K, Ottesen JL (2000) Meiosis-activating sterol-mediated resumption of meiosis in mouse oocytes in vitro is influenced by protein synthesis inhibition and cholera toxin. Biol Reprod 62: 775–780

    Article  PubMed  CAS  Google Scholar 

  • Guoliang X, Byskov AG, Andersen CY (1994) Cumulus cells secrete a meiosis-inducing substance by stimulation with forskolin and dibutyric cyclic adenosine monophosphate. Mol Reprod Dev 39: 17–24

    Article  CAS  Google Scholar 

  • Hardie DG, Carling D (1997) The AMP-activated protein kinase. Fuel gauge of the mammalian cell? Eur J Biochem 246: 259–273

    Article  PubMed  CAS  Google Scholar 

  • Hardie DG, Hawley SM (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. Bioessays (in press)

    Google Scholar 

  • Hegele-Hartung C, Kuhnke J, Les’ M, Grondahl C, Ottesen J, Beier HM, Eisner S, Eichenlaub-Ritter U (1999) Nuclear and cytoplasmic maturation of mouse oocytes after treatment with synthetic meiosis-activating sterol. Biol Reprod 61: 1362–1372

    Article  PubMed  CAS  Google Scholar 

  • Homa ST, Webster SD, Russell RK (1991) Phospholipid turnover and ultrastructural correlates during spontaneous germinal vesicle breakdown of the bovine oocyte: effects of a cyclic AMP phosphodiesterase inhibitor. Dev Biol 146: 461–472

    Article  PubMed  CAS  Google Scholar 

  • Larsen WJ, Wert S (1988) Roles of cell junctions in gametogenesis and in early embryonic development. Tissue Cell 20: 809–848

    Article  PubMed  CAS  Google Scholar 

  • Larsen WJ, Wert S, Brunner GD (1986) A dramatic loss of cumulus cell gap junctions is correlated with germinal vesicle breakdown in rat oocytes. Dev Biol 113: 517–521

    Article  PubMed  CAS  Google Scholar 

  • Larsen WJ, Wert S, Brunner GD (1987) Differential modulation of rat follicle cell gap junction populations at ovulation. Dev Biol 122: 61–71

    Article  PubMed  CAS  Google Scholar 

  • Pesty A, Lefevre B, Kubiak J, Geraud G, Tesarik J, Maro B (1994) Mouse oocyte maturation is affected by lithium via the polyphosphoinositide metabolism and the microtubule network. Mol Reprod Dev 38: 187–199

    Article  PubMed  CAS  Google Scholar 

  • Phillips DM, Dekel N (1991) Maturation of the rat cumulus-oocyte complex: structure and function. Mol Reprod Dev 28: 297–306

    Article  PubMed  CAS  Google Scholar 

  • Powers RD, Paleos GA (1982) Combined effects of calcium and dibutyryl cyclic AMP on germinal vesicle breakdown in the mouse oocyte. J Reprod Fertil 66: 1–8

    Article  PubMed  CAS  Google Scholar 

  • Racowsky C (1985a) Effect of forskolin on the spontaneous maturation and cyclic AMP content of hamster oocyte-cumulus complexes. J Exp Zool 234: 87–96

    Article  PubMed  CAS  Google Scholar 

  • Racowsky C (1985b) Effect of forskolin on maintenance of meiotic arrest and stimulation of cumulus expansion, progesterone and cyclic AMP production by pig oocyte-cumulus complexes. J Reprod Fertil 74: 9–21

    Article  PubMed  CAS  Google Scholar 

  • Racowsky C (1986) The releasing action of calcium upon cyclic AMP-dependent meiotic arrest in hamster oocytes. J Exp Zoo] 239: 263–275

    Article  CAS  Google Scholar 

  • Racowsky C, Baldwin KV (1989) In vitro and in vivo studies reveal that hamster oocyte meiotic arrest is maintained only transiently by follicular fluid, but persistently by membrana/cumulus cell contact. Dev Biol 134: 297–306

    Article  PubMed  CAS  Google Scholar 

  • Racoswky C, Baldwin KV, Larabell CA, DeMarais AA, Kazilek CJ (1989) Down-regulation of membrana granulosa cell gap junctions is correlated with irreversible commitment to resume meiosis in golden Syrian hamster oocytes. Eur J Cell Biol 49: 244–251

    Google Scholar 

  • Ruan B, Watanabe S, Eppig JJ, Kwoh C, Dzidic N, Pang J, Wilson WK, Schroepfer GJ Jr (1998) Sterols affecting meiosis: novel chemical syntheses and biological activities and spectral properties of the synthetic sterols. J Lipid Res 39: 2005–2020

    PubMed  CAS  Google Scholar 

  • Schultz RM, Montgomery RR, Belanoff JR (1983a) Regulation of mouse oocyte maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol 97: 264–273

    Article  PubMed  CAS  Google Scholar 

  • Schultz RM, Montgomery RR, Ward-Bailey PF, Eppig JJ (1983b) Regulation of oocyte maturation in the mouse: possible roles of intercellular communication, cAMP, and testosterone. Dev Biol 95: 294–304

    Article  PubMed  CAS  Google Scholar 

  • Schultz RM (1986) Molecular aspects of mammalian oocyte growth and maturation. In: Rossant J, Pederson RA (eds) Experimental approaches to mam-malian embryonic development. Cambridge University Press, Cambridge, pp 195–237

    Google Scholar 

  • Shitsukawa K, Andersen CB, Richard FJ, Horner AK, Wiersma A, van Duin M, Conti M (2001) Cloning and characterization of the cyclic guanosine monophosphate-inhibited phosphodiesterase PDE3A expressed in mouse oocyte. Biol Reprod 65: 188–196

    Article  PubMed  CAS  Google Scholar 

  • Sullivan JE, Brocklehurst KJ, Marley AE, Carey F, Carling D, Beri RK (1994) Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AI-CAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett 353: 33–36

    Article  PubMed  CAS  Google Scholar 

  • Tsafriri A (1988) Local nonsteroidal regulators of ovarian function. In: Knobil E, Neill J et al (eds) The physiology of reproduction. Raven Press, New York, pp 527–565

    Google Scholar 

  • Tsafriri A, Bar-Ami S (1978) Role of divalent cations in the resumption of meiosis of rat oocytes. J Exp Zool 205: 293–300

    Article  PubMed  CAS  Google Scholar 

  • Tsafriri A, Chun SY, Hsueh MW, Conti M (1996) Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol 178: 393–402

    Article  PubMed  CAS  Google Scholar 

  • Tsafriri A, Popliker M, Nahum R, Beyth Y (1998) Effects of ketoconazole on ovulatory changes in the rat: implications on the role of a meiosis-activating sterol. Mol Hum Reprod 4: 483–489

    Article  PubMed  CAS  Google Scholar 

  • Vaknin KM, Lazar S, Popliker M, Tsafriri A (2001) Role of meiosis-activating sterols in rat oocyte maturation: effects of specific inhibitors and changes in the expression of lanosterol 14a-demethylase during the preovulatory period. Biol Reprod 64: 299–309

    Article  PubMed  CAS  Google Scholar 

  • Vivarelli E, Conti M, De Felici M, Siracusa G (1983) Meiotic resumption and intracellular cAMP levels in mouse oocytes treated with compounds which act on cAMP metabolism. Cell Differ 12: 271–276

    Article  PubMed  CAS  Google Scholar 

  • Wert S, Larsen WJ (1990) Preendocytotic alterations in cumulus cell gap junctions precede meiotic resumption in the rat cumulus-oocyte complex. Tissue Cell 22: 827–851

    Article  PubMed  CAS  Google Scholar 

  • Wiersma A, Hirsch B, Tsafriri A, Hanssen RGJM, Van de Kant M, Kloosterboer HJ, Conti M, Hsueh AJW (1998) Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents. J Clin Invest 102: 532–537

    Article  PubMed  CAS  Google Scholar 

  • Winder WW, Hardie DG (1999) AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am J Physiol Metab 40:El—E10

    Google Scholar 

Download references

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Downs, S.M. (2002). The Biochemistry of Oocyte Maturation. In: Eppig, J., Hegele-Hartung, C., Lessl, M. (eds) The Future of the Oocyte. Ernst Schering Research Foundation Workshop, vol 41. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-04960-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-662-04960-0_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-04962-4

  • Online ISBN: 978-3-662-04960-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics