Egg Activation


Egg activation is the process of converting the female gamete, known as an oocyte or egg, into a cell that can support embryogenesis. In many organisms, this process is triggered by the fertilising sperm, but some organisms trigger egg activation by other mechanisms. Here we review the physiological state of the egg before activation, the mechanisms used to initiate egg activation, and the downstream cellular changes that must occur for a successful transition into a developing embryo. We will consider egg activation as it occurs in both invertebrate and vertebrate model systems, highlighting key similarities and differences between them.

Key Concepts

  • Animal eggs must undergo a process of ‘activation’ to allow them to initiate embryo development.
  • Egg activation transitions a mature – but arrested – oocyte to a totipotent cell that can initiate mitosis and embryogenesis.
  • Activation is triggered by a rise in calcium that sweeps across the egg in wave(s).
  • The calcium wave is triggered by fertilisation in vertebrates, echinoderms, and molluscs and by sperm‐independent mechanical triggers in insects.
  • The calcium wave is propagated through release of calcium from internal stores.
  • The calcium rise triggers events including completion of meiosis, reorganisation of the sperm nucleus into a male pronucleus, translation of some stored maternal mRNAs and destruction of others in the egg, modulation of the phosphoproteome of the egg, and modification of the egg's membranes and external coverings to block fertilisation by additional sperm.

Keywords: oocyte; embryo; fertilisation; egg activation; calcium; meiosis; cortical granule; phospholipase C; IP3

Figure 1. Sperm‐induced calcium oscillations in the mouse egg. Changes in intracellular calcium were monitored with the fluorescent calcium indicator fura 2.
Figure 2. The calcium wave during Drosophila egg activation. The figure shows stills from a movie of a mature Drosophila oocyte as it is undergoing egg activation in vitro. The oocyte contains the calcium indicator GCaMP3, which was deposited into it by a female who expressed it in her germline. Initially the oocyte swells. Then, calcium levels (false‐coloured here; scale at right) increase at the oocyte poles (particularly the posterior pole, which is the one that shows the rise in vivo). A wave of increased calcium then sweeps across the egg, propagated although the action of IP3‐mediated calcium release from stores. The centre of the egg has lower calcium levels because it is the site of the yolk. Scale bar, 200 µm. Reproduced from Kaneuchi et al. 2015 © PNAS.
Figure 3. Schematic diagram showing conserved major regulators of meiosis II arrest and resumption in vertebrates. Some details differ among vertebrates. For example, *Mos is required for both the establishment and maintenance of the metaphase II arrest in Xenopus, but only for the maintenance of the arrest in mouse. **p90RSK is dispensable for the metaphase II arrest in mouse. Also, in mouse, WEE1B, CDC25A and CDC25B (not shown) regulate the stability of CDK1; this has not been tested in Xenopus.


Aarhus R, Graeff RM, Dickey DM, Walseth TF and Lee HC (1995) ADP‐ribosyl cyclase and CD38 catalyze the synthesis of a calcium‐mobilizing metabolite from NADP. Journal of Biological Chemistry 270: 30327–30333.

Backs J, Stein P, Backs T, et al. (2010) The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proceedings of the National Academy of Sciences of the United States of America 107: 81–86.

Barckmann B, Pierson S, Dufourt J, et al. (2015) Aubergine iCLIP reveals piRNA‐dependent decay of mRNAs involved in germ cell development in the early embryo. Cell Reports 12: 1205–1216.

Benoit P, Papin C, Kwak JE, Wickens M and Simonelig M (2008) PAP‐ and GLD‐2‐type poly(A) polymerases are required sequentially in cytoplasmic polyadenylation and oogenesis in Drosophila. Development 135: 1969–1979.

Bernhardt ML, Kong BY, Kim AM, O'Halloran TV and Woodruff TK (2012) A zinc‐dependent mechanism regulates meiotic progression in mammalian oocytes. Biology of Reproduction 86: 114.

Bernhardt ML, Zhang Y, Erxleben CF, et al. (2015) CaV3.2 T‐type channels mediate Ca(2)(+) entry during oocyte maturation and following fertilization. Journal of Cell Science 128: 4442–4452.

Bianchi E, Doe B, Goulding D and Wright GJ (2014) Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature 508: 483–487.

Burkart AD, Xiong B, Baibakov B, Jimenez‐Movilla M and Dean J (2012) Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy. Journal of Cell Biology 197: 37–44.

Bushati N, Stark A, Brennecke J and Cohen SM (2008) Temporal reciprocity of miRNAs and their targets during the maternal‐to‐zygotic transition in Drosophila. Current Biology 18: 501–506.

Chen J, Melton C, Suh N, et al. (2011) Genome‐wide analysis of translation reveals a critical role for deleted in azoospermia‐like (Dazl) at the oocyte‐to‐zygote transition. Genes & Development 25: 755–766.

Coll O, Villalba A, Bussotti G, Notredame C and Gebauer F (2010) A novel, noncanonical mechanism of cytoplasmic polyadenylation operates in Drosophila embryogenesis. Genes & Development 24: 129–134.

Colledge WH, Carlton MB, Udy GB and Evans MJ (1994) Disruption of c‐mos causes parthenogenetic development of unfertilized mouse eggs. Nature 370: 65–68.

Cui J, Sartain CV, Pleiss JA and Wolfner MF (2013) Cytoplasmic polyadenylation is a major mRNA regulator during oogenesis and egg activation in Drosophila. Developmental Biology 383: 121–131.

Cui J, Sackton KL, Horner VL, Kumar KE and Wolfner MF (2008) Wispy, the Drosophila homolog of GLD‐2, is required during oogenesis and egg activation. Genetics 178: 2017–2029.

Cui J, Lai YW, Sartain CV, Zuckerman RM and Wolfner MF (2016) The Drosophila prage gene, required for maternal transcript destabilization in embryos, encodes a predicted RNA exonuclease. G3 (Bethesda) 6: 1687–1693.

Dahanukar A, Walker JA and Wharton RP (1999) Smaug, a novel RNA‐binding protein that operates a translational switch in Drosophila. Molecular Cell 4: 209–218.

Dingwall C and Laskey RA (1990) Nucleoplasmin: the archetypal molecular chaperone. Seminars in Cell Biology 1: 11–17.

Ducibella T, Huneau D, Angelichio E, et al. (2002) Egg‐to‐embryo transition is driven by differential responses to Ca2+ oscillation number. Developmental Biology 250: 280–291.

Dumont J, Umbhauer M, Rassinier P, Hanauer A and Verlhac MH (2005) p90Rsk is not involved in cytostatic factor arrest in mouse oocytes. Journal of Cell Biology 169: 227–231.

Duncan FE, Que EL, Zhang N, et al. (2016) The zinc spark is an inorganic signature of human egg activation. Scientific Reports 6: 24737.

Eichhorn SW, Subtelny AO, Kronja I, et al. (2016) mRNA poly(A)‐tail changes specified by deadenylation broadly reshape translation in Drosophila oocytes and early embryos. eLife 5: e16955.

Fang G, Yu H and Kirschner MW (1998) The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase‐promoting complex to control anaphase initiation. Genes & Development 12: 1871–1883.

Galione A, Morgan AJ, Arredouani A, et al. (2010) NAADP as an intracellular messenger regulating lysosomal calcium‐release channels. Biochemical Society Transactions 38: 1424–1431.

Giraldez AJ, Mishima Y, Rihel J, et al. (2006) Zebrafish MiR‐430 promotes deadenylation and clearance of maternal mRNAs. Science 312: 75–79.

Guo H, Garcia‐Vedrenne AE, Isserlin R, et al. (2015) Phosphoproteomic network analysis in the sea urchin Strongylocentrotus purpuratus reveals new candidates in egg activation. Proteomics 15: 4080–4095.

Hachem A, Godwin J, Ruas M, et al. (2017) PLCzeta is the physiological trigger of the Ca2+ oscillations that induce embryogenesis in mammals but conception can occur in its absence. Development 144: 2914–2924.

Hashimoto N, Watanabe N, Furuta Y, et al. (1994) Parthenogenetic activation of oocytes in c‐mos‐deficient mice. Nature 370: 68–71.

Horner VL, Czank A, Jang JK, et al. (2006) The Drosophila calcipressin sarah is required for several aspects of egg activation. Current Biology 16: 1441–1446.

Hughes SE, Gilliland WD, Cotitta JL, et al. (2009) Heterochromatic threads connect oscillating chromosomes during prometaphase I in Drosophila oocytes. PLoS Genetics 5(1): e1000348.

Igusa Y and Miyazaki S (1983) Effects of altered extracellular and intracellular calcium concentration on hyperpolarizing responses of the hamster egg. Journal of Physiology 340: 611–632.

Inoue N, Ikawa M, Isotani A and Okabe M (2005) The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434: 234–238.

Inoue D, Ohe M, Kanemori Y, Nobui T and Sagata N (2007) A direct link of the Mos‐MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs. Nature 446: 1100–1104.

Ivanovska I, Lee E, Kwan KM, Fenger DD and Orr‐Weaver TL (2004) The Drosophila MOS ortholog is not essential for meiosis. Curr. Biol. 14: 75–80.

Jaffe LA (1976) Fast block to polyspermy in sea urchin eggs is electrically mediated. Nature 261: 68–71.

Kaneuchi T, Sartain CV, Takeo S, et al. (2015) Calcium waves occur as Drosophila oocytes activate. Proceedings of the National Academy of Sciences of the United States of America 112: 791–796.

Kang H, Hwang SC, Park YS and Oh JS (2013) Cdc25B phosphatase participates in maintaining metaphase II arrest in mouse oocytes. Molecules and Cells 35: 514–518.

Kim AM, Bernhardt ML, Kong BY, et al. (2011) Zinc sparks are triggered by fertilization and facilitate cell cycle resumption in mammalian eggs. ACS Chemical Biology 6: 716–723.

Kleinschmidt JA, Dingwall C, Maier G and Franke WW (1986) Molecular characterization of a karyophilic, histone‐binding protein: cDNA cloning, amino acid sequence and expression of nuclear protein N1/N2 of Xenopus laevis. EMBO Journal 5: 3547–3552.

Kline D (1988) Calcium‐dependent events at fertilization of the frog egg: injection of a calcium buffer blocks ion channel opening, exocytosis, and formation of pronuclei. Developmental Biology 126: 346–361.

Kline D and Kline JT (1992) Thapsigargin activates a calcium influx pathway in the unfertilized mouse egg and suppresses repetitive calcium transients in the fertilized egg. Journal of Biological Chemistry 267: 17624–17630.

Knott JG, Kurokawa M, Fissore RA, Schultz RM and Williams CJ (2005) Transgenic RNA interference reveals role for mouse sperm phospholipase C zeta in triggering Ca2+ oscillations during fertilization. Biology of Reproduction 72: 992–996.

Krauchunas AR, Horner VL and Wolfner MF (2012) Protein phosphorylation changes reveal new candidates in the regulation of egg activation and early embryogenesis in D. melanogaster. Developmental Biology 370: 125–134.

Kronja I, Whitfield ZJ, Yuan B, et al. (2014) Quantitative proteomics reveals the dynamics of protein changes during Drosophila oocyte maturation and the oocyte‐to‐embryo transition. Proceedings of the National Academy of Sciences of the United States of America 111: 16023–16028.

Lee K, Davis A, Zhang L, et al. (2015) Pig oocyte activation using a Zn(2)(+) chelator, TPEN. Theriogenology 84: 1024–1032.

Li Y, Gorbea C, Mahaffey D, Rechsteiner M and Benezra R (1997) MAD2 associates with the cyclosome/anaphase‐promoting complex and inhibits its activity. Proceedings of the National Academy of Sciences of the United States of America 94: 12431–12436.

Lin CJ, Koh FM, Wong P, Conti M and Ramalho‐Santos M (2014) Hira‐mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote. Developmental Cell 30: 268–279.

Loeb J (1913) Artificial Parthenogenesis and Fertilization. Chicago: University of Chicago Press.

Loppin B, Bonnefoy E, Anselme C, et al. (2005) The histone H3.3 chaperone HIRA is essential for chromatin assembly in the male pronucleus. Nature 437: 1386–1390.

Ma J, Fukuda Y and Schultz RM (2015) Mobilization of dormant Cnot7 mRNA promotes deadenylation of maternal transcripts during mouse oocyte maturation. Biology of Reproduction 93: 48.

McKim KS, Jang JK, Theurkauf WE, and Hawley RS (1993) Mechanical basis of meiosis arrest. Nature 362: 364–366.

Medvedev S, Yang J, Hecht NB and Schultz RM (2008) CDC2A (CDK1)‐mediated phosphorylation of MSY2 triggers maternal mRNA degradation during mouse oocyte maturation. Developmental Biology 321: 205–215.

Miao YL, Stein P, Jefferson WN, Padilla‐Banks E and Williams CJ (2012) Calcium influx‐mediated signaling is required for complete mouse egg activation. Proceedings of the National Academy of Sciences of the United States of America 109: 4169–4174.

Miyazaki S, Yuzaki M, Nakada K, et al. (1992) Block of Ca2+ wave and Ca2+ oscillation by antibody to the inositol 1,4,5‐trisphosphate receptor in fertilized hamster eggs. Science 257: 251–255.

Mochida S and Hunt T (2007) Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature 449: 336–340.

Morin N, Abrieu A, Lorca T, Martin F and Doree M (1994) The proteolysis‐dependent metaphase to anaphase transition: calcium/calmodulin‐dependent protein kinase II mediates onset of anaphase in extracts prepared from unfertilized Xenopus eggs. EMBO Journal 13: 4343–4352.

Nishiyama T, Ohsumi K and Kishimoto T (2007) Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature 446: 1096–1099.

Ogawa Y (1994) Role of ryanodine receptors. Critical Reviews in Biochemistry and Molecular Biology 29: 229–274.

Oh JS, Susor A, Schindler K, Schultz RM and Conti M (2013) Cdc25A activity is required for the metaphase II arrest in mouse oocytes. Journal of Cell Science 126: 1081–1085.

Paillard L, Omilli F, Legagneux V, et al. (1998) EDEN and EDEN‐BP, a cis element and an associated factor that mediate sequence‐specific mRNA deadenylation in Xenopus embryos. EMBO Journal 17: 278–287.

Paillard L, Maniey D, Lachaume P, Legagneux V and Osborne HB (2000) Identification of a C‐rich element as a novel cytoplasmic polyadenylation element in Xenopus embryos. Mechanisms of Development 93: 117–125.

Paillard L, Legagneux V and Beverley OH (2003) A functional deadenylation assay identifies human CUG‐BP as a deadenylation factor. Biology of the Cell 95: 107–113.

Patel S, Marchant JS and Brailoiu E (2010) Two‐pore channels: regulation by NAADP and customized roles in triggering calcium signals. Cell Calcium 47: 480–490.

Payne C, Rawe V, Ramalho‐Santos J, Simerly C and Schatten G (2003) Preferentially localized dynein and perinuclear dynactin associate with nuclear pore complex proteins to mediate genomic union during mammalian fertilization. Journal of Cell Science 116: 4727–4738.

Perreault SD, Wolff RA and Zirkin BR (1984) The role of disulfide bond reduction during mammalian sperm nuclear decondensation in vivo. Developmental Biology 101: 160–167.

Pesin JA and Orr‐Weaver TL (2007) Developmental role and regulation of cortex, a meiosis‐specific anaphase‐promoting complex/cyclosome activator. PLoS Genetics 3: e202.

Philpott A, Leno GH and Laskey RA (1991) Sperm decondensation in Xenopus egg cytoplasm is mediated by nucleoplasmin. Cell 65: 569–578.

Potireddy S, Vassena R, Patel BG and Latham KE (2006) Analysis of polysomal mRNA populations of mouse oocytes and zygotes: dynamic changes in maternal mRNA utilization and function. Developmental Biology 298: 155–166.

Ray‐Gallet D, Quivy JP, Scamps C, et al. (2002) HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis. Molecular Cell 9: 1091–1100.

Renault AD, Zhang XH, Alphey LS, et al. (2003) Giant nuclei is essential in the cell cycle transition from meiosis to mitosis. Development 130: 2997–3005.

Rouget C, Papin C, Boureux A, et al. (2010) Maternal mRNA deadenylation and decay by the piRNA pathway in the early Drosophila embryo. Nature 467: 1128–1132.

Roux MM, Townley IK, Raisch M, et al. (2006) A functional genomic and proteomic perspective of sea urchin calcium signaling and egg activation. Developmental Biology 300: 416–433.

Sackton KL, Lopez JM, Berman CL and Wolfner MF (2009) YA is needed for proper nuclear organization to transition between meiosis and mitosis in Drosophila. BMC Developmental Biology 9: 43.

Satouh Y, Nozawa K, Yamagata K, Fujimoto T and Ikawa M (2017) Viable offspring after imaging of Ca2+ oscillations and visualization of the cortical reaction in mouse eggs. Biology of Reproduction 96: 563–575.

Saunders CM, Larman MG, Parrington J, et al. (2002) PLC zeta: a sperm‐specific trigger of Ca2+ oscillations in eggs and embryo development. Development 129: 3533–3544.

Shearer J, De Nadai C, Emily‐Fenouil F, et al. (1999) Role of phospholipase C gamma at fertilization and during mitosis in sea urchin eggs and embryos. Development 126: 2273–2284.

Swan A and Schüpbach T (2007) The Cdc20 (Fzy)/Cdh1‐related protein, Cort, cooperates with Fzy in cyclin destruction and anaphase progression in meiosis I and II in Drosophila. Development 134: 891–899.

Tadros W, Houston SA, Bashirullah A, et al. (2003) Regulation of maternal transcript destabilization during egg activation in Drosophila. Genetics 164: 989–1001.

Tadros W, Goldman AL, Babak T, et al. (2007) SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase. Developmental Cell 12: 143–155.

Takeo S, Tsuda M, Akahori S, Matsuo T and Aigaki T (2006) The calcineurin regulator Sra plays an essential role in female meiosis in Drosophila. Current Biology 16: 1435–1440.

Takeo S, Hawley RS and Aigaki T (2010) Calcineurin and its regulation by Sra/RCAN is required for completion of meiosis in Drosophila. Developmental Biology 344: 957–967.

Takeo S, Swanson SK, Nandanan K, et al. (2012) Shaggy/glycogen synthase kinase 3 beta and phosphorylation of Sarah/regulator of calcineurin are essential for completion of Drosophila female meiosis. Proceedings of the National Academy of Sciences of the United States of America 109: 6382–6389.

Tosca L, Glass R, Bronchain O, Philippe L and Ciapa B (2012) PLCgamma, G‐protein of the G alpha q type and cADPr pathway are associated to trigger the fertilization Ca2+ signal in the sea urchin egg. Cell Calcium 52: 388–396.

Tsurumi C, Hoffmann S, Geley S, Graeser R and Polanski Z (2004) The spindle assembly checkpoint is not essential for CSF arrest of mouse oocytes. Journal of Cell Biology 167: 1037–1050.

Tunquist BJ, Eyers PA, Chen LG, Lewellyn AL and Maller JL (2003) Spindle checkpoint proteins Mad1 and Mad2 are required for cytostatic factor‐mediated metaphase arrest. Journal of Cell Biology 163: 1231–1242.

Vacquier VD (2012) The quest for the sea urchin egg receptor for sperm. Biochemical and Biophysical Research Communications 425: 583–587.

Voeltz GK and Steitz JA (1998) AUUUA sequences direct mRNA deadenylation uncoupled from decay during Xenopus early development. Molecular and Cellular Biology 18: 7537–7545.

Xu Z, Kopf GS and Schultz RM (1994) Involvement of inositol 1,4,5‐trisphosphate‐mediated Ca2+ release in early and late events of mouse egg activation. Development 120: 1851–1859.

York‐Andersen AH, Parton RM, Bi CJ, et al. (2015) A single and rapid calcium wave at egg activation in Drosophila. Biology Open 4: 553–560.

Zhang N, Duncan FE, Que EL, O'Halloran TV and Woodruff TK (2016) The fertilization‐induced zinc spark is a novel biomarker of mouse embryo quality and early development. Scientific Reports 6: 22772.

Further Reading

Kashir J, Deguchi R, Jones C, Coward K and Stricker SA (2013) Comparative biology of sperm factors and fertilization‐induced calcium signals across the animal kingdom. Molecular Reproduction and Development 80: 787–815.

Krauchunas AR and Wolfner MF (2013) Molecular changes during egg activation. Current Topics in Developmental Biology 102: 267–292.

Miao YL and Williams CJ (2012) Calcium signaling in mammalian egg activation and embryo development: the influence of subcellular localization. Molecular Reproduction and Development 79: 742–756.

Swann K and Lai FA (2016) Egg activation at fertilization by a soluble sperm protein. Physiological Reviews 96: 127–149.

Walser CB and Lipshitz HD (2011) Transcript clearance during the maternal‐to‐zygotic transition. Current Opinion in Genetics & Development 21: 431–443.

Von Stetina JR and Orr‐Weaver TL (2011) Developmental control of oocyte maturation and egg activation in metazoan models. Cold Spring Harbor Perspectives in Biology 3: a005553.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Zhang, Zijing, Wolfner, Mariana F, and Williams, Carmen J(Jan 2018) Egg Activation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0003300.pub2]