Abstract
Oocytes are made in the fetal ovary and are only ever fertilized some Âconsiderable time later in the adult. During this time, they have to undergo two meiotic divisions (meiosis I and II), which must be executed faithfully and on time so as to produce a mature egg, with a haploid chromosome content, that is ovulated into the fallopian tube ready to be fertilized. The two meiotic divisions are controlled by both internal and external (hormonal) triggers, principally executed by changes in the activity of the kinase CDK1 in the oocyte. Here, we focus on how the oocyte controls CDK1 activity at three important time points: (1) the arrest at prophase I in the ovary and the hormone-driven release from this arrest, (2) the progression through meiosis I, and finally (3) the rearrest at metaphase II and subsequent completion of meiosis triggered by a sperm calcium signal.
Keywords
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009;9:153–66.
Ma HT, Poon RY. How protein kinases co-ordinate mitosis in animal cells. Biochem J. 2011;435:17–31.
Sorensen RA, Wassarman PM. Relationship between growth and meiotic maturation of the mouse oocyte. Dev Biol. 1976;50:531–6.
Kanatsu-Shinohara M, Schultz RM, Kopf GS. Acquisition of meiotic competence in mouse oocytes: absolute amounts of p34(cdc2), cyclin B1, cdc25C, and wee1 in meiotically incompetent and competent oocytes. Biol Reprod. 2000;63:1610–6.
Chesnel F, Eppig JJ. Synthesis and accumulation of p34cdc2 and cyclin B in mouse oocytes during acquisition of competence to resume meiosis. Mol Reprod Dev. 1995;40:503–8.
de Vantery C, Stutz A, Vassalli JD, Schorderet-Slatkine S. Acquisition of meiotic competence in growing mouse oocytes is controlled at both translational and posttranslational levels. Dev Biol. 1997;187:43–54.
Fulka Jr J, Flechon JE, Motlik J, Fulka J. Does autocatalytic amplification of maturation-promoting factor (MPF) exist in mammalian oocytes? Gamete Res. 1988;21:185–92.
Mattioli M, Galeati G, Bacci ML, Barboni B. Changes in maturation-promoting activity in the cytoplasm of pig oocytes throughout maturation. Mol Reprod Dev. 1991;30:119–25.
Tatemoto H, Horiuchi T. Requirement for protein synthesis during the onset of meiosis in bovine oocytes and its involvement in the autocatalytic amplification of maturation-promoting factor. Mol Reprod Dev. 1995;41:47–53.
Sullivan M, Morgan DO. Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol. 2007;8:894–903.
Pincus G, Enzmann EV. The comparative behavior of mammalian eggs in vivo and in vitro: I. The activation of ovarian eggs. J Exp Med. 1935;62:665–75.
Jones KT. Turning it on and off: M-phase promoting factor during meiotic maturation and fertilization. Mol Hum Reprod. 2004;10:1–5.
Lorca T, Labbe JC, Devault A, Fesquet D, Capony JP, Cavadore JC, et al. Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase. EMBO J. 1992;11:2381–90.
Solomon MJ, Lee T, Kirschner MW. Role of phosphorylation in p34cdc2 activation: identification of an activating kinase. Mol Biol Cell. 1992;3:13–27.
Fujii W, Nishimura T, Kano K, Sugiura K, Naito K. CDK7 and CCNH Are components of CDK-activating kinase and Are required for meiotic progression of pig oocytes. Biol Reprod. 2011;85:1124–32.
Lincoln AJ, Wickramasinghe D, Stein P, Schultz RM, Palko ME, De Miguel MP, et al. Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation. Nat Genet. 2002;30:446–9.
Duckworth BC, Weaver JS, Ruderman JV. G2 arrest in Xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A. Proc Natl Acad Sci USA. 2002;99:16794–9.
Han SJ, Chen R, Paronetto MP, Conti M. Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse. Curr Biol. 2005;15:1670–6.
Bornslaeger EA, Mattei P, Schultz RM. Involvement of cAMP-dependent protein kinase and protein phosphorylation in regulation of mouse oocyte maturation. Dev Biol. 1986;114:453–62.
Cho WK, Stern S, Biggers JD. Inhibitory effect of dibutyryl cAMP on mouse oocyte maturation in vitro. J Exp Zool. 1974;187:383–6.
Magnusson C, Hillensjo T. Inhibition of maturation and metabolism in rat oocytes by cyclic amp. J Exp Zool. 1977;201:139–47.
Freudzon L, Norris RP, Hand AR, Tanaka S, Saeki Y, Jones TL, et al. Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein. J Cell Biol. 2005;171:255–65.
Mehlmann LM, Jones TL, Jaffe LA. Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte. Science. 2002;297:1343–5.
Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, Pendola FL, et al. The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science. 2004;306:1947–50.
Hinckley M, Vaccari S, Horner K, Chen R, Conti M. The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes. Dev Biol. 2005;287:249–61.
Sela-Abramovich S, Galiani D, Nevo N, Dekel N. Inhibition of rat oocyte maturation and ovulation by nitric oxide: mechanism of action. Biol Reprod. 2008;78:1111–8.
Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, et al. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009;136:1869–78.
Vaccari S, Weeks 2nd JL, Hsieh M, Menniti FS, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009;81:595–604.
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;330:366–9.
Conti M, Andersen CB, Richard F, Mehats C, Chun SY, Horner K, et al. Role of cyclic nucleotide signaling in oocyte maturation. Mol Cell Endocrinol. 2002;187:153–9.
Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ. Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology. 2011;152:4377–85.
Zhang Y, Zhang Z, Xu XY, Li XS, Yu M, Yu AM, et al. Protein kinase A modulates Cdc25B activity during meiotic resumption of mouse oocytes. Dev Dyn. 2008;237:3777–86.
Han SJ, Conti M. New pathways from PKA to the Cdc2/cyclin B complex in oocytes: Wee1B as a potential PKA substrate. Cell Cycle. 2006;5:227–31.
Peters JM. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol. 2006;7:644–56.
Qiao X, Zhang L, Gamper AM, Fujita T, Wan Y. APC/C-Cdh1: from cell cycle to cellular differentiation and genomic integrity. Cell Cycle. 2010;9:3904–12.
Jones KT. Anaphase-promoting complex control in female mouse meiosis. Results Probl Cell Differ. 2011;53:343–63.
Reis A, Chang HY, Levasseur M, Jones KT. APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division. Nat Cell Biol. 2006;8:539–40.
Yamamuro T, Kano K, Naito K. Functions of FZR1 and CDC20, activators of the anaphase-promoting complex, during meiotic maturation of swine oocytes. Biol Reprod. 2008;79:1202–9.
Holt JE, Tran SM, Stewart JL, Minahan K, Garcia-Higuera I, Moreno S, et al. The APC/C activator FZR1 coordinates the timing of meiotic resumption during prophase I arrest in mammalian oocytes. Development. 2011;138:905–13.
Schindler K, Schultz RM. CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes. Biol Reprod. 2009;80:795–803.
Marangos P, Verschuren EW, Chen R, Jackson PK, Carroll J. Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1). J Cell Biol. 2007;176:65–75.
Oh JS, Han SJ, Conti M. Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption. J Cell Biol. 2010;188:199–207.
Holt JE, Weaver J, Jones KT. Spatial regulation of APCCdh1-induced cyclin B1 degradation maintains G2 arrest in mouse oocytes. Development. 2010;137:1297–304.
Marangos P, Carroll J. The dynamics of cyclin B1 distribution during meiosis I in mouse oocytes. Reproduction. 2004;128:153–62.
Kitajima TS, Ohsugi M, Ellenberg J. Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Cell. 2011;146:568–81.
Schindler K, Schultz RM. The CDC14A phosphatase regulates oocyte maturation in mouse. Cell Cycle. 2009;8:1090–8.
Ledan E, Polanski Z, Terret ME, Maro B. Meiotic maturation of the mouse oocyte requires an equilibrium between cyclin B synthesis and degradation. Dev Biol. 2001;232:400–13.
Reis A, Madgwick S, Chang HY, Nabti I, Levasseur M, Jones KT. Prometaphase APCcdh1 activity prevents non-disjunction in mammalian oocytes. Nat Cell Biol. 2007;9:1192–8.
Jin F, Hamada M, Malureanu L, Jeganathan KB, Zhou W, Morbeck DE, et al. Cdc20 is critical for meiosis I and fertility of female mice. PLoS Genet. 2010;6:e1001147.
Kudo NR, Anger M, Peters AH, Stemmann O, Theussl HC, Helmhart W, et al. Role of cleavage by separase of the Rec8 kleisin subunit of cohesin during mammalian meiosis I. J Cell Sci. 2009;122:2686–98.
Herbert M, Levasseur M, Homer H, Yallop K, Murdoch A, McDougall A. Homologue disjunction in mouse oocytes requires proteolysis of securin and cyclin B1. Nat Cell Biol. 2003;5:1023–5.
Gorr IH, Reis A, Boos D, Wuhr M, Madgwick S, Jones KT, et al. Essential CDK1-inhibitory role for separase during meiosis I in vertebrate oocytes. Nat Cell Biol. 2006;8:1035–7.
Jones KT. Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update. 2008;14:143–58.
Rieder CL, Cole RW, Khodjakov A, Sluder G. The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. J Cell Biol. 1995;130:941–8.
Li R, Murray AW. Feedback control of mitosis in budding yeast. Cell. 1991;66:519–31.
Hoyt MA, Totis L, Roberts BT. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell. 1991;66:507–17.
Lan W, Cleveland DW. A chemical tool box defines mitotic and interphase roles for Mps1 kinase. J Cell Biol. 2010;190:21–4.
Maresca TJ. Cell division: aurora B illuminates a checkpoint pathway. Curr Biol. 2011;21:R557–9.
Mansfeld J, Collin P, Collins MO, Choudhary JS, Pines J. APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol. 2011;13:1234–43.
Homer HA, McDougall A, Levasseur M, Yallop K, Murdoch AP, Herbert M. Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin during meiosis I in mouse oocytes. Genes Dev. 2005;19:202–7.
Homer H, Gui L, Carroll J. A spindle assembly checkpoint protein functions in prophase I arrest and prometaphase progression. Science. 2009;326:991–4.
Li M, Li S, Yuan J, Wang ZB, Sun SC, Schatten H, et al. Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis. PLoS One. 2009;4:e7701.
Hached K, Xie SZ, Buffin E, Cladiere D, Rachez C, Sacras M, et al. Mps1 at kinetochores is essential for female mouse meiosis I. Development. 2011;138:2261–71.
Lane SI, Chang HY, Jennings PC, Jones KT. The Aurora kinase inhibitor ZM447439 accelerates first meiosis in mouse oocytes by overriding the spindle assembly checkpoint. Reproduction. 2010;140:521–30.
McGuinness BE, Anger M, Kouznetsova A, Gil-Bernabe AM, Helmhart W, Kudo NR, et al. Regulation of APC/C activity in oocytes by a Bub1-dependent spindle assembly checkpoint. Curr Biol. 2009;19:369–80.
Nagaoka SI, Hodges CA, Albertini DF, Hunt PA. Oocyte-specific differences in cell-cycle control create an innate susceptibility to meiotic errors. Curr Biol. 2011;21:651–7.
Pinsky BA, Biggins S. The spindle checkpoint: tension versus attachment. Trends Cell Biol. 2005;15:486–93.
Khodjakov A, Pines J. Centromere tension: a divisive issue. Nat Cell Biol. 2010;12:919–23.
Masui Y, Markert CL. Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool. 1971;177:129–45.
Colledge WH, Carlton MBL, Udy GB, Evans MJ. Disruption of c-mos causes parthenogenetic development of unfertilized mouse eggs. Nature. 1994;370:65–8.
Hashimoto N, Watanabe N, Furuta Y, Tamemoto H, Sagata N, Yokoyama M, et al. Parthenogenetic activation of oocytes in c-mos-deficient mice. Nature. 1994;370:68–71.
Bhatt RR, Ferrell Jr JE. The protein kinase p90 rsk as an essential mediator of cytostatic factor activity. Science. 1999;286:1362–5.
Gross SD, Schwab MS, Lewellyn AL, Maller JL. Induction of metaphase arrest in cleaving Xenopus embryos by the protein kinase p90Rsk. Science. 1999;286:1365–7.
Gross SD, Schwab MS, Taieb FE, Lewellyn AL, Qian Y-W, Maller JL. The critical role of the MAP kinase pathway in meiosis II in Xenopus oocytes is mediated by p90Rsk. Curr Biol. 2000;10:430–8.
Dumont J, Umbhauer M, Rassinier P, Hanauer A, Verlhac MH. p90Rsk is not involved in cytostatic factor arrest in mouse oocytes. J Cell Biol. 2005;169:227–31.
Miyagaki Y, Kanemori Y, Baba T. Possible involvement of mitogen- and stress-activated protein kinase 1, MSK1, in metaphase-II arrest through phosphorylation of EMI2 in mouse oocytes. Dev Biol. 2011;359:73–81.
Liu J, Maller JL. Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. Curr Biol. 2005;15:1458–68.
Rauh NR, Schmidt A, Bormann J, Nigg EA, Mayer TU. Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. Nature. 2005;437:1048–52.
Tung JJ, Hansen DV, Ban KH, Loktev AV, Summers MK, Adler 3rd JR, et al. A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs. Proc Natl Acad Sci USA. 2005;102:4318–23.
Hansen DV, Tung JJ, Jackson PK. CaMKII and polo-like kinase 1 sequentially phosphorylate the cytostatic factor Emi2/XErp1 to trigger its destruction and meiotic exit. Proc Natl Acad Sci USA. 2006;103:608–13.
Liu J, Grimison B, Lewellyn AL, Maller JL. The anaphase-promoting complex/cyclosome inhibitor Emi2 is essential for meiotic but not mitotic cell cycles. J Biol Chem. 2006;281:34736–41.
Isoda M, Sako K, Suzuki K, Nishino K, Nakajo N, Ohe M, et al. Dynamic regulation of Emi2 by Emi2-bound Cdk1/Plk1/CK1 and PP2A-B56 in meiotic arrest of Xenopus eggs. Dev Cell. 2011;21:506–19.
Inoue D, Ohe M, Kanemori Y, Nobui T, Sagata N. A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs. Nature. 2007;446:1100–4.
Nishiyama T, Ohsumi K, Kishimoto T. Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature. 2007;446:1096–9.
Shoji S, Yoshida N, Amanai M, Ohgishi M, Fukui T, Fujimoto S, et al. Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J. 2006;25:834–45.
Madgwick S, Hansen DV, Levasseur M, Jackson PK, Jones KT. Mouse Emi2 is required to enter meiosis II by reestablishing cyclin B1 during interkinesis. J Cell Biol. 2006;174:791–801.
Suzuki T, Suzuki E, Yoshida N, Kubo A, Li H, Okuda E, et al. Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase. Development. 2010;137:3281–91.
Backs J, Stein P, Backs T, Duncan FE, Grueter CE, McAnally J, et al. The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proc Natl Acad Sci USA. 2009;107:81–6.
Chang HY, Minahan K, Merriman JA, Jones KT. Calmodulin-dependent protein kinase gamma 3 (CamKIIgamma3) mediates the cell cycle resumption of metaphase II eggs in mouse. Development. 2009;136:4077–81.
Oh JS, Susor A, Conti M. Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes. Science. 2011;332:462–5.
Mochida S, Hunt T. Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature. 2007;449:336–40.
Nishiyama T, Yoshizaki N, Kishimoto T, Ohsumi K. Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis. Nature. 2007;449:341–5.
Chang HY, Jennings PC, Stewart J, Verrills NM, Jones KT. Essential role of protein phosphatase 2A in metaphase II arrest and activation of mouse eggs shown by okadaic acid, dominant negative protein phosphatase 2A, and FTY720. J Biol Chem. 2011;286:14705–12.
Schmitz MH, Held M, Janssens V, Hutchins JR, Hudecz O, Ivanova E, et al. Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells. Nat Cell Biol. 2010;12:886–93.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag London
About this chapter
Cite this chapter
Jones, K.T., Lane, S.I.R., Holt, J.E. (2013). Start and Stop Signals of Oocyte Meiotic Maturation. In: Coticchio, G., Albertini, D., De Santis, L. (eds) Oogenesis. Springer, London. https://doi.org/10.1007/978-0-85729-826-3_13
Download citation
DOI: https://doi.org/10.1007/978-0-85729-826-3_13
Published:
Publisher Name: Springer, London
Print ISBN: 978-0-85729-825-6
Online ISBN: 978-0-85729-826-3
eBook Packages: MedicineMedicine (R0)