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: a sperm-specific trigger of Ca2+ oscillations in eggs and embryo development
1 Cell Signalling Laboratory, Wales Heart Research Institute, University of Wales College of Medicine, Cardiff CF14 4XN, UK
2 Department of Anatomy and Developmental Biology, University College, London WC1E 6BT, UK
3 Department of Physiology, University College, London WC1E 6BT, UK
*Author for correspondence (e-mail: lait{at}cf.ac.uk)
Accepted 1 May 2002
Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca2+ oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca2+ release. The ‘sperm factor’ hypothesis has not been ratified because a sperm-specific protein that generates repetitive Ca2+ transients and egg activation has not been found. We identify a novel, sperm-specific phospholipase C, PLC
, that triggers Ca2+ oscillations in mouse eggs indistinguishable from those at fertilisation. PLC removal from sperm extracts abolishes Ca2+ release in eggs. Moreover, the PLC content of a single sperm was sufficient to produce Ca2+ oscillations as well as normal embryo development to blastocyst. Our results are consistent with sperm PLC as the molecular trigger for development of a fertilised egg into an embryo.
Key words: Fertilisation, Sperm factor, Phospholipase C, Ca2+ oscillations, Egg activation, Mouse
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O. Lacham-Kaplan, J. Shaw, L. G. Sanchez-Partida, and A. Trounson Oocyte Activation after Intracytoplasmic Injection with Sperm Frozen Without Cryoprotectants Results in Live Offspring from Inbred and Hybrid Mouse Strains Biol Reprod, November 1, 2003; 69(5): 1683 - 1689. [Abstract] [Full Text] [PDF]
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K. Takenaka, K. Fukami, M. Otsuki, Y. Nakamura, Y. Kataoka, M. Wada, K. Tsuji, S.-I. Nishikawa, N. Yoshida, and T. Takenawa Role of Phospholipase C-L2, a Novel Phospholipase C-Like Protein That Lacks Lipase Activity, in B-Cell Receptor Signaling Mol. Cell. Biol., October 15, 2003; 23(20): 7329 - 7338. [Abstract] [Full Text] [PDF]
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K.-i. Sato, A. A. Tokmakov, C.-L. He, M. Kurokawa, T. Iwasaki, M. Shirouzu, R. A. Fissore, S. Yokoyama, and Y. Fukami Reconstitution of Src-dependent Phospholipase C{gamma} Phosphorylation and Transient Calcium Release by Using Membrane Rafts and Cell-free Extracts from Xenopus Eggs J. Biol. Chem., October 3, 2003; 278(40): 38413 - 38420. [Abstract] [Full Text] [PDF]
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M. Kurokawa and R. A. Fissore ICSI-generated mouse zygotes exhibit altered calcium oscillations, inositol 1,4,5-trisphosphate receptor-1 down-regulation, and embryo development Mol. Hum. Reprod., September 1, 2003; 9(9): 523 - 533. [Abstract] [Full Text] [PDF]
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 J. G. Alvarez Nurture vs Nature: How Can We Optimize Sperm Quality? J Androl, September 1, 2003; 24(5): 640 - 648. [Full Text] [PDF]
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 M. R. Wing, D. M. Bourdon, and T. K. Harden PLC-{varepsilon}: A Shared Effector Protein in Ras-, Rho-, and G{alpha}{beta}{gamma}-Mediated Signaling Mol. Interv., August 1, 2003; 3(5): 273 - 280. [Abstract] [Full Text] [PDF]
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P. Marangos, G. FitzHarris, and J. Carroll Ca2+ oscillations at fertilization in mammals are regulated by the formation of pronuclei Development, April 1, 2003; 130(7): 1461 - 1472. [Abstract] [Full Text] [PDF]
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C. Leckie, R. Empson, A. Becchetti, J. Thomas, A. Galione, and M. Whitaker The NO Pathway Acts Late during the Fertilization Response in Sea Urchin Eggs J. Biol. Chem., March 28, 2003; 278(14): 12247 - 12254. [Abstract] [Full Text] [PDF]
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 E. M. Adler, N. R. Gough, and L. B. Ray 2002: Signaling Breakthroughs of the Year Sci. Signal., January 7, 2003; 2003(164): eg1 - eg1. [Full Text] [PDF]
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 G. FitzHarris, P. Marangos, and J. Carroll Cell Cycle-dependent Regulation of Structure of Endoplasmic Reticulum and Inositol 1,4,5-Trisphosphate-induced Ca2+ Release in Mouse Oocytes and Embryos Mol. Biol. Cell, January 1, 2003; 14(1): 288 - 301. [Abstract] [Full Text]
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J. Tesarik Associated editor's comment: Calcium signalling in human oocytes and embryos: two-store model revival Hum. Reprod., November 1, 2002; 17(11): 2948 - 2949. [Full Text] [PDF]
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R. Dumollard, J. Carroll, G. Dupont, and C. Sardet Calcium wave pacemakers in eggs J. Cell Sci., September 15, 2002; 115(18): 3557 - 3564. [Abstract] [Full Text] [PDF]
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 B. Mueller-Roeber and C. Pical Inositol Phospholipid Metabolism in Arabidopsis. Characterized and Putative Isoforms of Inositol Phospholipid Kinase and Phosphoinositide-Specific Phospholipase C Plant Physiology, September 1, 2002; 130(1): 22 - 46. [Abstract] [Full Text] [PDF]
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