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The state of the union: the cell biology of fertilization

Nature Medicine volume 8, pages S57–S63 (2002)Cite this article

Abstract

Look at songs, hidden in eggs. Carl Sandburg in Prairie

Fertilization is the process by which sperm and egg unite. An expanded understanding of the mechanisms that underlie these events has provided insights into an important aspect of early development and also has proven to be a valuable model in which to study cellular function. In addition, many emerging strategies for contraception and for the treatment of infertility are based on the mechanism of gamete interaction. Here, we discuss the cell and molecular biology of mammalian fertilization, highlight selected recent breakthroughs and attempt to identify key unanswered questions.

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Figure 1: The sequence of early events in mammalian fertilization.
Figure 2: Triggering of the acrosome reaction.
Figure 3: Gamete membrane interactions and egg activation

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References

  1. Wilson, E.B. The cell in development and heredity 1–1232 (Macmillan, New York 1925).

  2. Maller, J.L. Maturation promoting factor in the early days. Trends Biochem. Sci. 20, 524–528 (1995).

    Article  CAS  PubMed  Google Scholar 

  3. Drewett, J.G. & Garbers, D.L. The family of guanylyl cyclase receptors and their ligands. Endocr. Rev. 15, 135–162 (1994).

    Article  CAS  PubMed  Google Scholar 

  4. Chen, Y. et al. Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289, 625–628 (2000).

    Article  CAS  PubMed  Google Scholar 

  5. Primakoff, P. & Myles, D.G. The ADAM gene family: surface proteins with adhesion and protease activity. Trends Genet. 16, 83–87 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. U.S. Census Bureau World Popclock. http://www.census.gov/cgi-bin/ipc/popclockw (2002).

  7. Wassarman, P.M., Jovine, L. & Litscher, E.S. A profile of fertilization in mammals. Nature Cell Biol. 3, E59–E64 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Wassarman, P.M. & Florman, H.M. Cellular mechanisms during mammalian fertilization. Handbook of Physiology: Section 14- Cell Physiology 885–938 (Oxford University Press, New York, 1997).

    Google Scholar 

  9. Yanagimachi, R. The Physiology of Reproduction 189–317 (Raven Press, New York 1994).

    Google Scholar 

  10. Myles, D.G. & Primakoff, P. Why did the sperm cross the cumulus – to get to the oocyte: functions of the sperm surface proteins PH-20 and fertilin in arriving at and fusing with the egg. Biol.Reprod. 56, 320–327 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Snell, W.J. & White, J.M. The molecules of mammalian fertilization. Cell 85, 629–637 (1996).

    Article  CAS  PubMed  Google Scholar 

  12. Vacquier, V.D. Evolution of gamete recognition proteins. Science 281, 1995–1998 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Visconti, P.E. et al. The molecular basis of sperm capacitation. J. Androl. 19, 242–248 (1998).

    CAS  PubMed  Google Scholar 

  14. Florman, H.M., Arnoult, C., Kazam, I.G., Li, C. & O'Toole, C.M.B. An intimate biochemistry: egg-regulated acrosome reactions of mammalian sperm. Adv. Devel. Biochem. 5, 147–186 (1999).

    Google Scholar 

  15. Visconti, P.E. et al. Novel signaling pathways involved in sperm acquisition of fertilizing capacity. J. Reprod. Immunol. 53, 133–150 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Wiesner, B. et al. Cyclic nucleotide-gated channels on the flagellum control Ca2+ entry into sperm. J. Cell Biol. 142, 473–484 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Ho, H.C. & Suarez, S.S. Hyperactivation of mammalian spermatozoa: function and regulation. Reproduction 122, 519–526 (2001).

    Article  CAS  PubMed  Google Scholar 

  18. Arnoult, C. et al. Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation. Proc.Natl Acad. Sci. USA 96, 6757–6762 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Visconti, P.E. et al. Cholesterol efflux-mediated signal transduction in mammalian sperm: cholesterol release signals an increase in protein tyrosine phosphorylation during mouse sperm capacitation. Dev. Biol. 214, 429–443 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. Contreras, H.R. & Llanos, M.N. Detection of progesterone receptors in human spermatozoa and their correlation with morphological and functional properties. Int. J. Androl. 24, 246–252 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Bleil, J.D. & Wassarman, P.M. Autoradiographic visualization of the mouse egg's sperm receptor bound to sperm. J. Cell Biol. 102, 1363–1371 (1986).

    Article  CAS  PubMed  Google Scholar 

  22. Bleil, J.D. & Wassarman, P.M. Mammalian sperm–egg interaction: identification of a glycoprotein in mouse egg zonae pellucidae possessing receptor activity for sperm. Cell 20, 873–882 (1980).

    Article  CAS  PubMed  Google Scholar 

  23. Florman, H.M. & Wassarman, P.M. O-linked oligosaccharides of mouse egg ZP3 account for its sperm receptor activity. Cell 41, 313–324 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wassarman, P.M. & Litscher, E.S. Towards the molecular basis of sperm and egg interaction during mammalian fertilization. Cells Tissues Organs 168, 36–45 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Easton, R.L. et al. Structural analysis of murine zona pellucida glycans. Evidence for the expression of core 2-type O-glycans and the Sda antigen. J. Biol. Chem. 275, 7731–7742 (2000).

    Article  CAS  PubMed  Google Scholar 

  26. Hardy, D.M. & Garbers, D.L. A sperm membrane protein that binds in a species-specific manner to the egg extracellular matrix is homologous to von Willebrand factor. J. Biol. Chem. 270, 26025–26028 (1995).

    Article  CAS  PubMed  Google Scholar 

  27. Hardy, D.M. & Garbers, D.L. Species-specific binding of sperm proteins to the extracellular matrix (zona pellucida) of the egg. J. Biol. Chem. 269, 19000–19004 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Chen, J., Litscher, E.S. & Wassarman, P.M. Inactivation of the mouse sperm receptor, mZP3, by site-directed mutagenesis of individual serine residues located at the combining site for sperm. Proc. Natl Acad. Sci. USA 95, 6193–6197 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Macek, M.B., Lopez, L.C. & Shur, B.D. Aggregation of β-1,4-galactosyltransferase on mouse sperm induces the acrosome reaction. Dev. Biol. 147, 440–444 (1991).

    Article  CAS  PubMed  Google Scholar 

  30. Gong, X., Dubois, D.H., Miller, D.J. & Shur, B.D. Activation of a G protein complex by aggregation of β-1,4-galactosyltransferase on the surface of sperm. Science 269, 1718–1721 (1995).

    Article  CAS  PubMed  Google Scholar 

  31. Koyota, S., Wimalasiri, K.M. & Hoshi, M. Structure of the main saccharide chain in the acrosome reaction-inducing substance of the starfish, Asterias amurensis. J. Biol. Chem. 272, 10372–10376 (1997).

    Article  CAS  PubMed  Google Scholar 

  32. Hirohashi, N. & Vacquier, V.D. High molecular mass egg fucose sulfate polymer is required for opening both Ca2+ channels involved in triggering the sea urchin sperm acrosome reaction. J. Biol. Chem. 277, 1182–1189 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Arnoult, C., Cardullo, R.A., Lemos, J.R. & Florman, H.M. Activation of mouse sperm T-type Ca2+ channels by adhesion to the egg zona pellucida. Proc. Natl Acad. Sci. USA 93, 13004–13009 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ward, C.R., Storey, B.T. & Kopf, G.S. Selective activation of Gi1 and Gi2 in mouse sperm by the zona pellucida, the egg's extracellular matrix. J. Biol. Chem. 269, 13254–13258 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Tomes, C.N., McMaster, C.R. & Saling, P.M. Activation of mouse sperm phosphatidylinositol-4,5 bisphosphate-phospholipase C by zona pellucida is modulated by tyrosine phosphorylation. Mol. Reprod. Dev. 43, 196–204 (1996).

    Article  CAS  PubMed  Google Scholar 

  36. Fukami, K. et al. Requirement of phospholipase Cδ4 for the zona pellucida-induced acrosome reaction. Science 292, 920–923 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Roldan, E.R.S., Murase, T. & Shi, Q.-X. Exocytosis in spermatozoa in response to progesterone and zona pellucida. Science 266, 1578–1581 (1994).

    Article  CAS  PubMed  Google Scholar 

  38. Florman, H.M., Tombes, R.M., First, N.L. & Babcock, D.F. An adhesion-associated agonist from the zona pellucida activates G protein-promoted elevations of internal Ca and pH that mediate mammalian sperm acrosomal exocytosis. Dev. Biol. 135, 133–146 (1989).

    Article  CAS  PubMed  Google Scholar 

  39. Arnoult, C., Zeng, Y., & Florman, H.M. ZP3-dependent activation of sperm cation channels regulates acrosomal secretion during mammalian fertilization. J. Cell Biol. 134, 637–645 (1996).

    Article  CAS  PubMed  Google Scholar 

  40. Florman, H.M. Sequential focal and global elevations of sperm intracellular Ca2+ are initiated by the zona pellucida during acrosomal exocytosis. Dev. Biol. 165, 152–164 (1994).

    Article  CAS  PubMed  Google Scholar 

  41. Minke, B. & Cook, B. TRP Channel Proteins and Signal Transduction. Physiol. Rev. 82, 429–472 (2002).

    Article  CAS  PubMed  Google Scholar 

  42. Wissenbach, U., Schroth, G., Phillipp, S. & Flockerzi, V. Structure and mRNA expression of a bovine trp homologue related to mammalian trp2 transcripts. FEBS Lett. 429, 61–66 (1998).

    Article  CAS  PubMed  Google Scholar 

  43. Jungnickel, M.K., Marrero, H., Birnbaumer, L., Lemos, J.R. & Florman, H.M. Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nature Cell Biol. 5, 499–502 (2001).

    Article  CAS  Google Scholar 

  44. Trevino, C.L., Serrano, C.J., Beltran, C., Felix, R. & Darszon, A. Identification of mouse trp homologs and lipid rafts from spermatogenic cells and sperm. FEBS Lett. 509, 119–125 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Walensky, L.D. & Snyder, S.H. Inositol 1,4,5-trisphosphate receptors selectively localized to the acrosomes of mammalian sperm. J. Cell Biol. 130, 857–869 (1995).

    Article  CAS  PubMed  Google Scholar 

  46. Wes, P.D. et al. TRPC1, a human homolog of a Drosophila store-operated channel. Proc. Natl Acad. Sci. USA 92, 9652–9656 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vannier, B. et al. Mouse trp2, the homologue of the human trpc2 pseudogene, encodes mTrp2, a store depletion-activated capacitative Ca2+ channel. Proc. Natl Acad. Sci. USA 96, 2060–2064 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hutt, D.M., Cardullo, R.A., Baltz, J.M. & Kgsee, J.K. Synaptotagmin VIII Is localized to the mouse sperm head and may function in acrosomal exocytosis. Biol. Reprod. 66, 50–56 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Schulz, J.R., Wessel, G.M. & Vacquier, V.D. The exocytosis regulatory proteins syntaxin and VAMP are shed from sea urchin sperm during the acrosome reaction. Dev. Biol. 191, 80–87 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Michaut, M., Tomes, C.N., De Blas, G., Yunes, R. & Mayorga, L.S. Calcium-triggered acrosomal exocytosis in human spermatozoa requires the coordinated activation of Rab3A and N-ethylmaleimide-sensitive factor. Proc. Natl Acad. Sci. USA 97, 9996–10001 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Cummins, J.M. & Yanagimachi, R. Development of ability to penetrate the cumulus oophorus by hamster spermatozoa capacitated in vitro, in relation to the timing of the acrosome reaction. Gamete Res. 15, 187–212 (1986).

    Article  Google Scholar 

  52. Evans, J.P. Sperm disintegrins, egg integrins, and other cell adhesion molecules of mammalian gamete plasma membrane interactions. Front. Biosci. 4, D114–D131 (1999).

    CAS  PubMed  Google Scholar 

  53. Cuasnicu, P.S. et al. Molecular mechanisms involved in mammalian gamete fusion. Arch. Med. Res. 32, 614–618 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Cho, C. et al. Fertilization defects in sperm from mice lacking fertilin β. Science 281, 1857–1859 (1998).

    Article  CAS  PubMed  Google Scholar 

  55. Nishimura, H., Cho, C., Branciforte, D.R., Myles, D.G. & Primakoff, P. Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin β. Dev. Biol. 233, 204–213 (2001).

    Article  CAS  PubMed  Google Scholar 

  56. Zhu, X., Bansal, N.P. & Evans, J.P. Identification of key functional amino acids of the mouse fertilin β (ADAM2) disintegrin loop for cell–cell adhesion during fertilization. J. Biol. Chem. 275, 7677–7683 (2000).

    Article  CAS  PubMed  Google Scholar 

  57. Bigler, D. et al. Sequence-specific interaction between the disintegrin domain of mouse ADAM 2 (fertilin β) and murine eggs. Role of the α6 integrin subunit. J. Biol. Chem. 275, 11576–11584 (2000).

    Article  CAS  PubMed  Google Scholar 

  58. Takahashi, Y., Bigler, D., Ito, Y. & White, J.M. Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of β1 integrin-associated proteins CD9, CD81, and CD98. Mol. Biol. Cell 12, 809–820 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chen, M.S. et al. Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin α6β1: implications for murine fertilization. Proc. Natl Acad. Sci. USA 96, 11830–11835 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Almeida, E.A. et al. Mouse egg integrin α6β1 functions as a sperm receptor. Cell 81, 1095–1104 (1995).

    Article  CAS  PubMed  Google Scholar 

  61. Chen, H. & Sampson, N.S. Mediation of sperm–egg fusion: evidence that mouse egg α6β1 integrin is the receptor for sperm fertilin β. Chem. Biol. 6, 1–10 (1999).

    Article  PubMed  Google Scholar 

  62. Miller, B.J., Georges-Labouesse, E., Primakoff, P. & Myles, D.G. Normal fertilization occurs with eggs lacking the integrin α6β1 and is CD9-dependent. J. Cell Biol. 149, 1289–1296 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Evans, J.P. Fertilin β and other ADAMs as integrin ligands: insights into cell adhesion and fertilization. BioEssays 23, 628–639 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Zhu, X. & Evans, J.P. Analysis of the roles of RGD-binding integrins, α4/α9 integrins, α6 integrins, and CD9 in the interaction of the fertilin β (ADAM2) disintegrin domain with the mouse egg membrane. Biol. Reprod. 66, 1193–1202 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Eto, K. et al. Functional Classification of ADAMs Based on a Conserved Motif for Binding to Integrin α9β1. Implications for sperm–egg binding and other cell interactions. J. Biol. Chem. 277, 17804–17810 (2002).

    Article  CAS  PubMed  Google Scholar 

  66. Le Naour, F., Rubinstein, E., Jasmin, C., Prenant, M. & Boucheix, C. Severely reduced female fertility in CD9-deficient mice. Science 287, 319–321 (2000).

    Article  CAS  PubMed  Google Scholar 

  67. Miyado, K. et al. Requirement of CD9 on the egg plasma membrane for fertilization. Science 287, 321–324 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Kaji, K. et al. The gamete fusion process is defective in eggs of CD9-defective mice. Nature Genet. 24, 279–282 (2000).

    Article  CAS  PubMed  Google Scholar 

  69. Zhu, G.Z. et al. Residues SFQ (173–175) in the large extracellular loop of CD9 are required for gamete fusion. Development 129, 1995–2002 (2002).

    Article  CAS  PubMed  Google Scholar 

  70. Wong, G.E., Zhu, X., Prater, C.E., Oh, E. & Evans, J.P. Analysis of fertilin α (ADAM1)-mediated sperm-egg cell adhesion during fertilization and identification of an adhesion-mediating sequence in the disintegrin-like domain. J. Biol. Chem. 276, 24937–24945 (2001).

    Article  CAS  PubMed  Google Scholar 

  71. Hemler, M.E. Specific tetraspanin functions. J. Cell Biol. 155, 1103–1107 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Boucheix, C. & Rubinstein, E. Tetraspanins. Cell Mol. Life Sci. 58, 1189–1205 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Blobel, C.P. et al. A potential fusion peptide and an integrin ligand domain in a protein active in sperm–egg fusion. Nature 356, 248–252 (1992).

    Article  CAS  PubMed  Google Scholar 

  74. Shamsadin, R. et al. Male mice deficient for germ-cell cyritestin are infertile. Biol. Reprod. 61, 1445–1451 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Ulrich, A.S., Otter, M., Glabe, C.G. & Hoekstra, D. Membrane fusion is induced by a distinct peptide sequence of the sea urchin fertilization protein bindin. J. Biol. Chem. 273, 16748–16755 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Kresge, N., Vacquier, V.D. & Stout, C.D. The crystal structure of a fusagenic sperm protein reveals extreme surface properties. Biochemistry 40, 5407–5413 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Runft, L.L., Jaffe, L.A. & Mehlmann, L.M. Egg activation at fertilization: where it all begins. Dev. Biol. 245, 237–254 (2002).

    Article  CAS  PubMed  Google Scholar 

  78. Stricker, S.A. Comparative biology of calcium signaling during fertilization and egg activation in animals. Dev. Biol. 211, 157–176 (1999).

    Article  CAS  PubMed  Google Scholar 

  79. Jones, K.T., Carroll, J., Merriman, J.A., Whittingham, D.G. & Kono, T. Repetitive sperm-induced Ca2+ transients in mouse oocytes are cell cycle dependent. Development 121, 3259–3266 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Schultz, R.M. & Kopf, G.S. Molecular basis of mammalian egg activation. Curr. Top. Dev. Biol. 30, 21–62 (1995).

    Article  CAS  PubMed  Google Scholar 

  81. Kline, D. & Kline, J.T. Repetitive calcium transients and the role of calcium in exocytosis and cell cycle activation in the mouse egg. Dev. Biol. 145, 80–89 (1992).

    Article  Google Scholar 

  82. Giusti, A.F., Carroll, D.J., Abassi, Y.A. & Foltz, K.R. Evidence that a starfish egg Src family tyrosine kinase associates with PLC-γ1 SH2 domains at fertilization. Dev. Biol. 208, 189–199 (1999).

    Article  CAS  PubMed  Google Scholar 

  83. Giusti, A.F. et al. Requirement of a Src family kinase for initiating calcium release at fertilization in starfish eggs. J. Biol. Chem. 274, 29318–29322 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Giusti, A.F., Xu, W., Hinkle, B., Terasaki, M. & Jaffe, L.A. Evidence that fertilization activates starfish eggs by sequential activation of a Src-like kinase and phospholipase Cγ. J. Biol. Chem. 275, 16788–16794 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Kinsey, W.H. & Shen, S.S. Role of the Fyn kinase in calcium release during fertilization of the sea urchin egg. Dev. Biol. 225, 253–264 (2000).

    Article  CAS  PubMed  Google Scholar 

  86. Runft, L.L. & Jaffe, L.A. Sperm extract injection into ascidian eggs signals Ca2+ release by the same pathway as fertilization. Development 127, 3227–3236 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Carroll, D.J. et al. Calcium release at fertilization in starfish eggs is mediated by phospholipase Cγ. J. Cell Biol. 138, 1303–1311 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Carroll, D.J., Albay, D.T., Terasaki, M., Jaffe, L.A. & Foltz, K.R. Identification of PLCγ-dependent and -independent events during fertilization of sea urchin eggs. Dev.Biol. 206, 232–247 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Mehlmann, L.M., Carpenter, G., Rhee, S.G. & Jaffe, L.A. SH2 domain-mediated activation of phospholipase Cγ is not required to initiate Ca2+ release at fertilization of mouse eggs. Dev. Biol. 203, 221–232 (1998).

    Article  CAS  PubMed  Google Scholar 

  90. Mehlmann, L.M., Chattopadhyay, A., Carpenter, G., & Jaffe, L.A. Evidence that phospholipase C from the sperm is not responsible for initiating Ca2+ release at fertilization in mouse eggs. Dev. Biol. 236, 492–501 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Moore, G.D., Ayabe, T., Visconti, P.E., Schultz, R.M. & Kopf, G.S. Roles of heterotrimeric and monomeric G proteins in sperm-induced activation of mouse eggs. Development 120, 3313–3323 (1994).

    Article  CAS  PubMed  Google Scholar 

  92. Williams, C.J., Mehlmann, L.M., Jaffe, L.A., Kopf, G.S. & Schultz, R.M. Evidence that Gq family G proteins do not function in mouse egg activation at fertilization. Dev. Biol. 198, 116–127 (1998).

    CAS  PubMed  Google Scholar 

  93. Campbell, K.D., Reed, W.A. & White, K.L. Ability of integrins to mediate fertilization, intracellular calcium release, and parthenogenetic development in bovine oocytes. Biol. Reprod. 62, 1702–1709 (2000).

    Article  CAS  PubMed  Google Scholar 

  94. Iwao, Y. & Fujimura, T. Activation of Xenopus eggs by RGD-containing peptides accompanied by intracellular Ca2+ release. Dev. Biol. 177, 558–567 (1996).

    Article  CAS  PubMed  Google Scholar 

  95. Shilling, F.M., Magie, C.R. & Nuccitelli, R. Voltage-dependent activation of frog eggs by a sperm surface disintegrin peptide. Dev. Biol. 202, 113–124 (1998).

    Article  CAS  PubMed  Google Scholar 

  96. Tesarik, J. & Mendoza, C. In vitro fertilization by intracytoplasmic sperm injection. BioEssays 21, 791–801 (1999).

    CAS  Google Scholar 

  97. Kuretake, S., Kimura, Y., Hoshi, K. & Yanagimachi, R. Fertilization and development of mouse oocytes injected with isolated sperm heads. Biol.Reprod. 55, 789–795 (1996).

    Article  CAS  PubMed  Google Scholar 

  98. Kimura, Y. et al. Analysis of mouse oocyte activation suggests the involvement of sperm perinuclear material. Biol.Reprod. 58, 1407–1415 (1998).

    Article  CAS  PubMed  Google Scholar 

  99. Parrington, J., Swann, K., Shevchenko, V.I., Sesay, A.K. & Lai, F.A. Calcium oscillations in mammalian eggs triggered by a soluble sperm protein. Nature 379, 364–368 (1996).

    Article  CAS  PubMed  Google Scholar 

  100. Sette, C., Bevilacqua, A., Geremia, R., & Rossi, P. Involvement of phospholipase Cγ1 in mouse egg activation induced by a truncated form of the C-kit tyrosine kinase present in spermatozoa. J. Cell Biol. 142, 1063–1074 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Wolosker, H. et al. Molecularly cloned mammalian glucosamine-6-phosphate deaminase localizes to transporting epithelium and lacks oscillin activity. FASEB J. 12, 91–99 (1998).

    CAS  PubMed  Google Scholar 

  102. Wolny, Y.M. et al. Human glucosamine-6-phosphate isomerase, a homologue of hamster oscillin, does not appear to be involved in Ca2+ release in mammalian oocytes. Mol. Reprod. Dev. 52, 277–287 (1999).

    Article  CAS  PubMed  Google Scholar 

  103. Kuo, R.C. et al. NO is necessary and sufficient for egg activation at fertilization. Nature 406, 633–636 (2000).

    Article  CAS  PubMed  Google Scholar 

  104. Hyslop, L.A., Carroll, M., Nixon, V.L., McDougall, A. & Jones, K.T. Simultaneous measurement of intracellular nitric oxide and free calcium levels in chordate eggs demonstrates that nitric oxide has no role at fertilization. Dev. Biol. 234, 216–230 (2001).

    Article  CAS  PubMed  Google Scholar 

  105. Rice, A., Parrington, J., Jones, K.T. & Swann, K. Mammalian sperm contain a Ca2+-sensitive phospholipase C activity that can generate InsP(3) from PIP(2) associated with intracellular organelles. Dev. Biol. 228, 125–135 (2000).

    Article  CAS  PubMed  Google Scholar 

  106. Heyers, S. et al. Activation of mouse oocytes requires multiple sperm factors but not sperm PLCγ1. Mol. Cell Endocrinol. 166, 51–57 (2000).

    Article  CAS  PubMed  Google Scholar 

  107. Wu, H. et al. Sperm factor induces intracellular free calcium oscillations by stimulating the phosphoinositide pathway. Biol. Reprod. 64, 1338–1349 (2001).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the members of our laboratories for valuable discussions and the National Institutes of Health for supporting our efforts.

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  1. Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, 21205, MD, USA

    Janice P. Evans

  2. Department of Cell Biology, University of Massachusetts Medical School, Worcester, 01655, MA, USA

    Harvey M. Florman

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Correspondence to Janice P. Evans or Harvey M. Florman.

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Evans, J., Florman, H. The state of the union: the cell biology of fertilization. Nat Med 8 (Suppl 10), S57–S63 (2002). https://doi.org/10.1038/nm-fertilityS57

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