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15 - Egg activation: initiation and decoding of Ca2+ signaling

from Section 3 - Developmental biology

Published online by Cambridge University Press:  05 October 2013

By
John Carroll  and
Karl Swann
Edited by
Alan Trounson ,
Roger Gosden  and
Ursula Eichenlaub-Ritter
John Carroll
Affiliation:
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia
Karl Swann
Affiliation:
Institute of Molecular and Experimental Medicine, Cardif University School of Medicine, Cardif, UK
Alan Trounson
Affiliation:
California Institute for Regenerative Medicine
Roger Gosden
Affiliation:
Center for Reproductive Medicine and Infertility, Cornell University, New York
Ursula Eichenlaub-Ritter
Affiliation:
Universität Bielefeld, Germany
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Summary

Introduction

Egg activation refers to the early events that occur in the egg (or oocyte) that start embryo development. The most significant of these events in mammals is the resumption of meiosis, which is evident as the emission of a second polar body and then the formation of two polar bodies. However, egg activation in mammals also includes the exocytosis of cortical granules which leads to modifications of the zona pellucida, and changes in the pattern of protein and RNA synthesis. In mammals the sperm initiates the events of egg activation. Egg activation can also be initiated by various chemical and physical stimuli, and by modulating the activity of some key cell-cycle proteins. These artificial agents lead to egg activation in the absence of a sperm, which is termed parthenogenetic activation. We review the sequence and mechanism of egg activation in mammals, concentrating upon data in the mouse.

Sperm-induced Ca2+ oscillations

The key change in the egg that initiates the events of egg activation is an increase in the cytosolic free Ca2+ concentration. It was shown more than 25 years ago that fertilization of mouse and hamster eggs is associated with a series of cytosolic Ca2+ oscillations [1, 2]. An example of such oscillations at fertilization in a mouse egg is shown in Figure 15.1. It can be seen that each Ca2+ increase lasts about a minute but that there are repeated Ca2+ transients that last for several hours. In mouse eggs these oscillations persist up until the time of the formation of pronuclei [3]. Similar Ca2+ oscillations have now been reported in fertilizing eggs of a number of other different mammalian species such as pigs, cows, horse, rats, and humans. There are slight differences in the exact form of the Ca2+ increase and in their frequency. In all cases the Ca2+spikes, or transient oscillations, are separated by at least 10 minutes, and the series as a whole lasts for several hours. In mouse eggs, the oscillations have been shown to be essential for the key events of activation since the introduction of Ca2+ chelators into the cytosol blocks meiotic resumption and exocytosis [4]. Furthermore, we know these Ca2+ increases are sufficient for egg activation because causing an artificial increase in intracellular Ca2+ by applying a Ca2+ ionophore, or by microinjecting Ca2+ directly into the eggs, triggers development up to the blastocyst stage [1].

Type
Chapter
Information
Biology and Pathology of the Oocyte
Role in Fertility, Medicine and Nuclear Reprograming
 , pp. 177 - 186
Publisher: Cambridge University Press
Print publication year: 2013

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References

Swann, K, Ozil, JP.Dynamics of the calcium signal that triggers mammalian egg activation. Int Rev Cytol 1994; 152: 183–222.CrossRefGoogle ScholarPubMed
Miyazaki, S, Shirakawa, H, Nakada, K, Honda, Y.Essential role of the inositol 1,4,5-trisphosphate/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs. Dev Biol 1993; 58: 62–78.CrossRefGoogle Scholar
Marangos, P, FitzHarris, G, Carroll, J.Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei. Development 2003; 130: 1461–72.CrossRefGoogle ScholarPubMed
Kline, D, Kline, T.Repetitive calcium transients and the role of calcium in exocytosis and cell cycle activation in the mouse egg. Dev Biol 1992; 149: 80–9.CrossRefGoogle ScholarPubMed
Deguchi, R, Shirakawa, H, Oda, S, Mohri, T, Miyazaki, S.Spatiotemporal analysis of Ca2+ waves in relation to the sperm entry site and animal-vegetal axis during Ca2+ oscillations in fertilized mouse eggs. Dev Biol 2000; 218: 299–313.CrossRefGoogle Scholar
Ducibella, T, Fissore, R.The roles of Ca2+, downstream protein kinases, and oscillatory signalling in regulating fertilization and the activation of development. Dev Biol 2007; 315: 257–79.CrossRefGoogle Scholar
Dumollard, R, Marangos, P, Fitzharris, G, et al. Sperm triggered Ca2+ oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development 2004; 131: 3057–67.CrossRefGoogle ScholarPubMed
Ajduk, A, Ilozue, T, Windsor, S, et al. Rhythmic actomyosin-driven contractions induced by sperm entry predict mammalian embryo viabilityNat Commun 2011; 2: 417.CrossRefGoogle ScholarPubMed
Lee, S, Yoon, Y, Fissore, RA, Regulation of fertilization-initiated [Ca2+]i oscillations in mammalian eggs: a multi-pronged approach. Semin Cell Dev Biol 2006; 17: 274–84.CrossRefGoogle ScholarPubMed
Swann, K.A cytosolic sperm factor stimulates repetitive calcium increases and mimics fertilization in hamster oocytes. Development 1990; 110: 1295–302.Google Scholar
Nomikos, M, Swann, K, Lai, FA.Starting a new life: sperm PLC-zeta mobilizes the Ca2+ signal that induces egg activation and embryo development: an essential phospholipase C with implications for male infertility. Bioessays 2012; 34: 126–34.CrossRefGoogle ScholarPubMed
Nakano, Y, Shirakawa, H, Mitsuhashi, N, Kuwubara, Y, Miyazaki, S. Spatiotemporal dynamics of intracellular calcium in the mouse egg injected with a spermatozoon. Mol Hum Reprod 1997; 3: 1087–93.CrossRefGoogle ScholarPubMed
Saunders, CM, Larman, MG, Parrington, J, et al. PLCζ: a sperm-specific trigger of Ca2+ oscillations in eggs and embryo development. Development 2002; 129: 3533–44.Google Scholar
Fujimoto, S, Yoshida, N, Fukui, T, et al. Mammalian phospholipase Cz induces oocyte activation from the sperm perinuclear matrix. Dev Biol 2004; 274: 370–83.CrossRefGoogle Scholar
Bedford-Guaus, SJ, McPartlin, LA, Xie, J, et al. Molecular cloning and characterization of phospholipase C zeta in equine sperm and testis reveals species-specific differences in expression of catalytically active protein. Biol Reprod 2011; 85: 78–88.CrossRefGoogle ScholarPubMed
Ito, M, Ngaoka, K, Kuroda, K, et al. Arrest of spermatogenesis at round spermatids in PLCz1 deficient mice. Abstract at the 11thInternational Symposium on Spermatology. Okinawa, Japan, 2010.Google Scholar
Knott, JG, Kurokawa, M, Fissore, RA, Schultz, RM, Williams, CJ.Transgenic RNAi reveals role for mouse sperm phospholipase Cz in triggering Ca2+ oscillations during fertilization. Biol Reprod 2005; 72: 992–6.CrossRefGoogle Scholar
Lee, BS, Yoon, Y, Malcuit, C, Parys, JB, Fissore, RA, Inositol 1,4,5-trisphosphate receptor 1 degradation in mouse eggs and impact on [Ca2+]i oscillations. J Cell Physiol 2010; 222: 238–47.CrossRefGoogle Scholar
Swann, K, Yu, Y.The dynamics of Ca2+ oscillations that activate mammalian eggs. Int J Dev Biol 2008; 52: 585–94.CrossRefGoogle Scholar
Nomikos, M, Yu, Y, Elgmati, K, et al. Phospholipase Cζ rescues failed oocyte activation in a protptype of male factor infertility. Fert Steril 2013; 99: 76–85.CrossRefGoogle Scholar
Phillips, SV, Yu, Y, Rossbach A, et al. Divergent effect of mammalian PLCζ in generating Ca2+ oscillations in somatic cells compared with eggs. Biochem J 2011; 438: 545–53.CrossRefGoogle Scholar
Yoshida, N, Amani, M, Kajikawa, E, et al. Broad, extopic expression of the sperm protein PLCZ1 induces parthenogenesis and ovarian tumours in mice. Development 2007; 134: 3941–52.CrossRefGoogle Scholar
Yu, Y, Nomikos, M, Theodoridou, M, et al. PLCζ causes Ca2+ oscillations in mouse eggs by targeting intracellular and not plasma membrane PI(4,5)P(2). Mol Biol Cell 2012; 23: 371–80.CrossRefGoogle Scholar
Kashir, J, Heindryckx, B, Jones, C, et al. Oocyte activation, phospholipase C zeta and human infertility. Hum Reprod Update 2010; 16: 690–703.CrossRefGoogle ScholarPubMed
Larman, MG, Saunders, CM, Carroll, J, Lai, FA, Swann, K.Cell cycle-dependent Ca2+ oscillations in mouse embryos are regulated by nuclear targeting of PLCzeta. J Cell Sci 2004; 117: 2513–21.CrossRefGoogle ScholarPubMed
Ito, M, Shikano, T, Oda, S, et al. Difference in Ca2+ oscillation-inducing activity and nuclear translocation ability of PLCZ1, an egg-activating sperm factor candidate, between mouse, rat, human, and medaka fish. Biol Reprod 2008; 78: 1081–90.CrossRefGoogle ScholarPubMed
Cuthbertson, KS, Whittingham, DG, Cobbold, PH.Free Ca2+ increases in exponential phases during mouse oocyte activation. Nature 1981; 294: 754–7.CrossRefGoogle ScholarPubMed
Halet, G, Tunwell, R, Parkinson, SJ, Carroll, J.Conventional PKCs regulate the temporal pattern of Ca2+ oscillations at fertilisation in mouse eggs. J Cell Biol 2004; 164: 1033–44.CrossRefGoogle ScholarPubMed
Oancea, E, Meyer, T.Protein, kinase Cas a molecular machine for decoding calcium and diacylglycerol signals. Cell 1998; 95: 307–18.CrossRefGoogle ScholarPubMed
Gallicano, GI, McGaughey, RW, Capco, DG.Activation of protein kinase C after fertilization is required for remodelling in the mouse egg into thezygote. Mol Reprod Dev 1997; 46: 587–601.3.0.CO;2-T>CrossRefGoogle Scholar
Tatone, C, DelleMonarche, S, Francione, A, et al. Ca2+-independent protein kinase C signalling in mouse eggs during the early phases of fertilization. Int J Dev Biol 2003; 47: 327–33.Google ScholarPubMed
Kalive, M, Faust, JJ, Koeneman, BA, Capco, DG.Involvement of the PKC family in regulation of early development. Mol Reprod Dev 2010 77: 95–104.Google ScholarPubMed
Viveiros, MM, Hirao, Y, Eppig, JJ.Evidence that protein kinase C (PKC) participates in the meiosis I to meiosis II transition in mouse oocytes. Dev Biol 2001; 235: 330–42.CrossRefGoogle ScholarPubMed
Viveiros, MM, O’Brien, M, Wigglesworth, K, Eppig, JJ.Characterization of protein kinase C-δ in mouse oocytes throughout meiotic maturation and following egg activation. Biol Reprod 2003; 69: 1494–9.CrossRefGoogle ScholarPubMed
Gonzalez-Garcia, JR, Machaty, Z, Lai, FA, Swann, K.The dynamics of PKC-induced phosphorylation triggered by Ca2+ oscillations in mouse eggs. J Cell Physiol 2013; 228: 110–19.CrossRefGoogle ScholarPubMed
Halet, G.PKC signaling at fertilization in mammalian eggs. Biochem Biophys Acta 2004; 1742: 185–9.CrossRefGoogle ScholarPubMed
Jones, KT.Protein, kinase Caction at fertilization: overstated or undervalued?Rev Reprod 1998; 3: 7–12.CrossRefGoogle ScholarPubMed
Yu, Y, Halet, G, Lai, FA, Swann, K.Regulation of diacylglycerol production and protein kinase C stimulation during sperm- and PLCzeta-mediated mouse egg activation. Biol Cell 2008; 100: 633–43.CrossRefGoogle ScholarPubMed
Lorca, T, Cruzalegui, FH, Fesquet, D, et al. Calmodulin-dependent protein kinase II mediates inactivation of MPF and CSF upon fertilization of Xenopus eggs. Nature 1993; 366: 270–3.CrossRefGoogle ScholarPubMed
Whitaker, M.Sharper than a needle. Nature 1993; 366: 211–12.CrossRefGoogle Scholar
Winston, NJ, Maro, B.Calmodulin-dependent protein kinase II is activated transiently in ethanol-stimulated mouse oocytes. Dev Biol 1995; 170: 350–2.CrossRefGoogle ScholarPubMed
Johnson, J, Bierle, BM, Gallicano, GI, Capco, DG.Calcium/calmodulin-dependent protein kinase II and calmodulin: regulators of the meiotic spindle in mouse eggs. Dev Biol 1998; 204: 464–77.CrossRefGoogle ScholarPubMed
Markoulaki, S, Matson, S, Abbott, AL, Ducibella, T.Oscillatory CaMKII activity in mouse egg activation. Dev Biol 2003; 258: 464–74.CrossRefGoogle ScholarPubMed
Markoulaki, S, Matson, S, Ducibella, T.Fertilization stimulates long-lasting oscillations of CaMKII activity in mouse eggs. Dev Biol 2004; 272: 15–25.CrossRefGoogle ScholarPubMed
Madgwick, S, Levasseur, M, Jones, KT.Calmondulin-dependent protein kinase II, and not protein kinase C, is sufficient for triggering cell-cycle resumption in mammalian eggs. J Cell Sci 2005; 118: 3849–59.CrossRefGoogle Scholar
Knott, JG, Gardner, AJ, Madgwick, S, et al. Calmodulindependent protein kinase II triggers mouse egg activation and embryo development in the absence of Ca2+ oscillations. Dev Biol 2006; 296: 388–95.CrossRefGoogle Scholar
Matson, S, Markoulaki, S, Ducibella, T, Antagonists of myosin light chain kinase and of myosin II inhibit specific events of egg activation in fertilized mouse eggs. Biol Reprod 2006; 74: 169–76.CrossRefGoogle ScholarPubMed
Leguia, M, Conner, S, Berg, L, Wessel, GM.Synaptotagmin 1 is involved in the regulation of cortical granule exocytosis in the sea urchin. Mol Reprod Dev 2006; 73: 895–905.CrossRefGoogle ScholarPubMed
Backs, J, Stein, P, Backs, T, et al. The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proc Natl Acad Sci USA 2010; 107: 81–6.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
Nixon, VL, Levasseur, M, McDougall, A, Jones, KT.Ca2+ oscillations promote APC/C-dependent cyclin B1 degradation during metaphase arrest and completion of meiosis in fertilizing mouse eggs. Curr Biol 2002; 12: 746–50.CrossRefGoogle Scholar
Marangos, P, Carroll, J.Fertilization and InsP3-induced Ca2+ release stimulate a persistent increase in the rate of degradation of cyclin B1 specifically in mature mouse oocytes. Dev Biol 2004; 272: 26–38.CrossRefGoogle ScholarPubMed
Tunquist, BJ, Maller, JL.Under arrest: cytostatic factor (CSF)-mediated metaphase arrest in vertebrate eggs. Genes Dev 2003; 17: 683–710.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Shoji, S, Yoshida, N, Amanai, M, et al. Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J 2006; 25: 834–45.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Tung, JJ, Hansen, DV, Ban, KH, 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Suzuki, T, Suzuki, E, Yoshida, N, et al. Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase. Development 2010; 137: 3281–91.CrossRefGoogle ScholarPubMed
Dupont, G, Heytens, E, Leybaert, L.Oscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach. Int J Dev Biol 2010; 54; 655–65.CrossRefGoogle ScholarPubMed
Rizzuto, R, De Stefani, D, Raffaello, A, Mammucari, C.Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 2012; 13: 566–78.CrossRefGoogle ScholarPubMed
Dumollard, R, Marangos, P, Fitzharris, G, et al. Sperm-triggered [Ca2+] oscillations and Ca2+ homeostasis in the mouse egg have an absolute requirement for mitochondrial ATP production. Development 2004; 131: 3057–67.CrossRefGoogle ScholarPubMed
Campbell, K, Swann, K.Ca2+ oscillations stimulate an ATP increase during fertilization of mouse eggs. Dev Biol 2006; 298: 225–33.CrossRefGoogle ScholarPubMed
Liu, L, Hammar, K, Smith, PJ, Inoue, S, Keefe, DL.Mitochondrial modulation of calcium signaling at the initiation of development. Cell Calcium 2001; 30: 423–33.CrossRefGoogle ScholarPubMed
De Stefani, D, Raffaello, A, Teardo, E, Szabò, I, Rizzuto, R.A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 2011; 476: 336–40.CrossRefGoogle ScholarPubMed
Leese, HJ.Metabolism of the preimplantation embryo: 40 years on. Reproduction 2012; 143: 417–27.CrossRefGoogle Scholar
Ozil, JP, Banrezes, B, Tóth, S, Pan, H, Schultz, RM. Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term. Dev Biol 2006; 300: 534–44.CrossRefGoogle ScholarPubMed
Rogers, NT, Halet, G, Piao, Y, et al. The absence of a Ca2+ signal during mouse egg activation can affect parthenogenetic preimplantation development, gene expression patterns, and blastocyst quality. Reproduction 2006; 132: 45–57.CrossRefGoogle Scholar
Ozil, JP, Huneau, D.Activation of rabbit oocytes: the impact of the Ca2+ signal regime on development. Development 2001; 128: 917–28.Google ScholarPubMed

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