Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T08:48:32.350Z Has data issue: false hasContentIssue false

Sperm–egg adhesion and fusion in mammals

Published online by Cambridge University Press:  01 April 2009

Peter Sutovsky
Affiliation:
Division of Animal Sciences and Department of Obstetrics, Gynecology and Women's Health, University of Missouri-Columbia, S141 ASRC, 920 East Campus Drive, Columbia, MO 65211-5300, USA. Tel: +1 573 882 3329; Fax: +1 573 884 5540; E-mail: sutovskyp@missouri.edu

Abstract

Fertilisation is an orchestrated, stepwise process during which the participating male and female gametes undergo irreversible changes, losing some of their structural components while contributing others to the resultant zygote. Following sperm penetration through the egg coat, the sperm plasma membrane fuses with its oocyte counterpart, the oolemma. At least two plasma membrane proteins essential for sperm–oolemma fusion – IZUMO and CD9 on the male and female gametes, respectively – have been identified recently by classical cell biology approaches and confirmed by gene deletion. Oolemma-associated tetraspanin CD81, closely related to CD9, also appears to have an essential role in fusion. Additional proteins that may have nonessential yet still facilitating roles in sperm–oolemma adhesion and fusion include oolemma-anchored integrins and oocyte-expressed retroviral envelope proteins, sperm disintegrins, and sperm-borne proteins of epididymal origin such as CRISP1 and CRISP2. This review discusses these components of the gamete fusion mechanism within the framework of gamete structure, membrane biology, cell signalling and cytoskeletal dynamics, and revisits the topic of antipolyspermy defence at the oolemma level. Harnessing the mechanisms of sperm–egg fusion is of importance to animal biotechnology and to human assisted fertilisation, wherein male patients with reduced sperm fusibility have been identified.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Suarez, S.S. and Pacey, A.A. (2006) Sperm transport in the female reproductive tract. Human Reproduction Update 12, 23-37CrossRefGoogle ScholarPubMed
2Primakoff, P. and Myles, D.G. (2007) Cell-cell membrane fusion during mammalian fertilization. FEBS Letters 581, 2174-2180CrossRefGoogle ScholarPubMed
3Inoue, N. et al. (2007) Sperm-egg interaction and gene manipulated animals. Society of Reproduction and Fertility Supplement 65, 363-371Google ScholarPubMed
4Vjugina, U. and Evans, J.P. (2008) New insights into the molecular basis of mammalian sperm-egg membrane interactions. Frontiers in Bioscience 13, 462-476CrossRefGoogle ScholarPubMed
5Wu, G.M. et al. (2004) Birth of piglets by in vitro fertilization of zona-free porcine oocytes. Theriogenology 62, 1544-1556CrossRefGoogle ScholarPubMed
6Sathananthan, A.H., ed. (1996) Visual Atlas of Human Sperm Structure and Function for Assisted Reproductive Technology, Department of Obstetrics & Gynaecology, National University of Singapore, SingaporeGoogle Scholar
7Yu, Y. et al. (2006) The extracellular protein coat of the inner acrosomal membrane is involved in zona pellucida binding and penetration during fertilization: characterization of its most prominent polypeptide (IAM38). Developmental Biology 290, 32-43CrossRefGoogle ScholarPubMed
8Yanagimachi, R. (1994) Mammalian fertilization. In The Physiology of Reproduction (2nd edn) (Knobil, E. and Neill, J., eds), pp. 189-317, Raven Press, New York, USAGoogle Scholar
9Manandhar, G. and Toshimori, K. (2001) Exposure of sperm head equatorin after acrosome reaction and its fate after fertilization in mice. Biology of Reproduction 65, 1425-1436CrossRefGoogle ScholarPubMed
10Toshimori, K. et al. (1998) An MN9 antigenic molecule, equatorin, is required for successful sperm-oocyte fusion in mice. Biology of Reproduction 59, 22-29CrossRefGoogle ScholarPubMed
11Yoshinaga, K. et al. (2001) Inhibition of mouse fertilization in vivo by intra-oviductal injection of an anti-equatorin monoclonal antibody. Reproduction 122, 649-655CrossRefGoogle ScholarPubMed
12Yamatoya, K. et al. (2008) Mammalian sperm MN9 antigen N-, O-sialoglycoprotin EQUATORIN: biochemical characterization and identification of the gene. Presented at the 41st Annual Meeting of the Society for the Study of Reproduction (27–30 May 2008; Kailua-Kona, Big Island, Hawaii), http://www.ssr.org/Documents/2008-05-25_058abstracts.pdfGoogle Scholar
13Okabe, M. et al. (1987) Capacitation-related changes in antigen distribution on mouse sperm heads and its relation to fertilization rate in vitro. Journal of Reproductive Immunology 11, 91-100CrossRefGoogle ScholarPubMed
14Inoue, N. et al. (2005) The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434, 234-238CrossRefGoogle ScholarPubMed
15Aricescu, A.R. and Jones, E.Y. (2007) Immunoglobulin superfamily cell adhesion molecules: zippers and signals. Current Opinion in Cell Biology 19, 543-550CrossRefGoogle ScholarPubMed
16Tarrant, J.M. et al. (2003) Tetraspanins: molecular organisers of the leukocyte surface. Trends in Immunology 24, 610-617CrossRefGoogle ScholarPubMed
17Lazo, P.A. (2007) Functional implications of tetraspanin proteins in cancer biology. Cancer Science 98, 1666-1677CrossRefGoogle ScholarPubMed
18Yunta, M. and Lazo, P.A. (2003) Tetraspanin proteins as organisers of membrane microdomains and signalling complexes. Cellular Signalling 15, 559-564CrossRefGoogle ScholarPubMed
19Espenel, C. et al. (2008) Single-molecule analysis of CD9 dynamics and partitioning reveals multiple modes of interaction in the tetraspanin web. Journal of Cell Biology 182, 765-776CrossRefGoogle ScholarPubMed
20Chen, M.S. et al. (1999) Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin alpha6beta1: implications for murine fertilization. Proceedings of the National Academy of Sciences of the United States of America 96, 11830-11835CrossRefGoogle ScholarPubMed
21Le Naour, F. et al. (2000) Severely reduced female fertility in CD9-deficient mice. Science 287, 319-321CrossRefGoogle ScholarPubMed
22Kaji, K. et al. (2000) The gamete fusion process is defective in eggs of Cd9-deficient mice. Nature Genetics 24, 279-282CrossRefGoogle ScholarPubMed
23Miyado, K. et al. (2000) Requirement of CD9 on the egg plasma membrane for fertilization. Science 287, 321-324CrossRefGoogle ScholarPubMed
24Rubinstein, E. et al. (2006) Reduced fertility of female mice lacking CD81. Developmental Biology 290, 351-358CrossRefGoogle ScholarPubMed
25Kaji, K. et al. (2002) Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm-egg fusion. Developmental Biology 247, 327-334CrossRefGoogle ScholarPubMed
26Flint, M. et al. (1999) Characterization of hepatitis C virus E2 glycoprotein interaction with a putative cellular receptor, CD81. Journal of Virology 73, 6235-6244CrossRefGoogle ScholarPubMed
27Tanigawa, M. et al. (2008) Possible involvement of CD81 in acrosome reaction of sperm in mice. Molecular Reproduction and Development 75, 150-155CrossRefGoogle ScholarPubMed
28Miyado, K. et al. (2008) The fusing ability of sperm is bestowed by CD9-containing vesicles released from eggs in mice. Proceedings of the National Academy of Sciences of the United States of America 105, 12921-12926CrossRefGoogle ScholarPubMed
29Ellerman, D.A. et al. (2003) Direct binding of the ligand PSG17 to CD9 requires a CD9 site essential for sperm-egg fusion. Molecular Biology of the Cell 14, 5098-5103CrossRefGoogle ScholarPubMed
30Runge, K.E. et al. (2007) Oocyte CD9 is enriched on the microvillar membrane and required for normal microvillar shape and distribution. Developmental Biology 304, 317-325CrossRefGoogle ScholarPubMed
31Bronson, R.A. and Fusi, F. (1990) Evidence that an Arg-Gly-Asp adhesion sequence plays a role in mammalian fertilization. Biology of Reproduction 43, 1019-1025CrossRefGoogle Scholar
32Bronson, R.A. and Fusi, F. (1990) Sperm-oolemmal interaction: role of the Arg-Gly-Asp (RGD) adhesion peptide. Fertility and Sterility 54, 527-529CrossRefGoogle ScholarPubMed
33Blobel, C.P. et al. (1992) A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion. Nature 356, 248-252CrossRefGoogle Scholar
34Almeida, E.A. et al. (1995) Mouse egg integrin alpha 6 beta 1 functions as a sperm receptor. Cell 81, 1095-1104CrossRefGoogle ScholarPubMed
35Miller, B.J. et al. (2000) Normal fertilization occurs with eggs lacking the integrin alpha6beta1 and is CD9-dependent. Journal of Cell Biology 149, 1289-1296CrossRefGoogle ScholarPubMed
36Cho, C. et al. (1998) Fertilization defects in sperm from mice lacking fertilin beta. Science 281, 1857-1859CrossRefGoogle ScholarPubMed
37Nishimura, H. et al. (2001) Analysis of loss of adhesive function in sperm lacking cyritestin or fertilin beta. Developmental Biology 233, 204-213CrossRefGoogle ScholarPubMed
38Shamsadin, R. et al. (1999) Male mice deficient for germ-cell cyritestin are infertile. Biology of Reproduction 61, 1445-1451CrossRefGoogle ScholarPubMed
39Roberts, K.P. et al. (2007) Structure and function of epididymal protein cysteine-rich secretory protein-1. Asian Journal of Andrology 9, 508-514CrossRefGoogle ScholarPubMed
40Cohen, D.J. et al. (2007) Participation of epididymal cysteine-rich secretory proteins in sperm-egg fusion and their potential use for male fertility regulation. Asian Journal of Andrology 9, 528-532CrossRefGoogle ScholarPubMed
41Cohen, D.J. et al. (2000) Relationship between the association of rat epididymal protein “DE” with spermatozoa and the behavior and function of the protein. Molecular Reproduction and Development 56, 180-1883.0.CO;2-4>CrossRefGoogle ScholarPubMed
42Rochwerger, L. and Cuasnicu, P.S. (1992) Redistribution of a rat sperm epididymal glycoprotein after in vitro and in vivo capacitation. Molecular Reproduction and Development 31, 34-41CrossRefGoogle ScholarPubMed
43Da Ros, V.G. et al. (2008) Impaired sperm fertilizing ability in mice lacking Cysteine-RIch Secretory Protein 1 (CRISP1). Developmental Biology 320, 12-18CrossRefGoogle ScholarPubMed
44Busso, D. et al. (2007) Evidence for the involvement of testicular protein CRISP2 in mouse sperm-egg fusion. Biology of Reproduction 76, 701-708CrossRefGoogle ScholarPubMed
45Maleszewski, M., Kimura, Y. and Yanagimachi, R. (1996) Sperm membrane incorporation into oolemma contributes to the oolemma block to sperm penetration: evidence based on intracytoplasmic sperm injection experiments in the mouse. Molecular Reproduction and Development 44, 256-2593.0.CO;2-0>CrossRefGoogle Scholar
46Wortzman-Show, G.B. et al. (2007) Calcium and sperm components in the establishment of the membrane block to polyspermy: studies of ICSI and activation with sperm factor. Molecular Human Reproduction 13, 557-565CrossRefGoogle ScholarPubMed
47Gundersen, G.G. and Shapiro, B.M. (1984) Sperm surface proteins persist after fertilization. Journal of Cell Biology 99, 1343-1353CrossRefGoogle ScholarPubMed
48Gabel, C.A., Eddy, E.M. and Shapiro, B.M. (1979) After fertilization, sperm surface components remain as a patch in sea urchin and mouse embryos. Cell 18, 207-215CrossRefGoogle ScholarPubMed
49Nishioka, D. et al. (1987) Dispersal of sperm surface antigens in the plasma membranes of polyspermically fertilized sea urchin eggs. Experimental Cell Research 173, 628-632CrossRefGoogle ScholarPubMed
50Krukowska, A. et al. (1998) Mouse oocytes and parthenogenetic eggs lose the ability to be penetrated by spermatozoa after fusion with zygotes. Zygote 6, 321-328CrossRefGoogle ScholarPubMed
51Iwao, Y. and Fujimura, T. (1996) Activation of Xenopus eggs by RGD-containing peptides accompanied by intracellular Ca2+ release. Developmental Biology 177, 558-567CrossRefGoogle ScholarPubMed
52Campbell, K.D., Reed, W.A. and White, K.L. (2000) Ability of integrins to mediate fertilization, intracellular calcium release, and parthenogenetic development in bovine oocytes. Biology of Reproduction 62, 1702-1709CrossRefGoogle ScholarPubMed
53Tatone, C. and Carbone, M.C. (2006) Possible involvement of integrin-mediated signalling in oocyte activation: evidence that a cyclic RGD-containing peptide can stimulate protein kinase C and cortical granule exocytosis in mouse oocytes. Reproductive Biology and Endocrinology 4, 48CrossRefGoogle ScholarPubMed
54Fenichel, P. and Durand-Clement, M. (1998) Role of integrins during fertilization in mammals. Human Reproduction 13 Supplement 4, 31-46CrossRefGoogle ScholarPubMed
55Sessions, B.R. et al. (2006) Effects of amino acid substitutions in and around the arginine-glycine-aspartic acid (RGD) sequence on fertilization and parthenogenetic development in mature bovine oocytes. Molecular Reproduction and Development 73, 651-657CrossRefGoogle ScholarPubMed
56McLaughlin, E.A. et al. (2001) Do fertilin beta and cyritestin play a major role in mammalian sperm–oolemma interactions? A critical re-evaluation of the use of peptide mimics in identifying specific oocyte recognition protiens. Molecular Human Reproduction 7, 313-317CrossRefGoogle Scholar
57Longo, F.J. (1985) Fine structure of the mammalian egg cortex. American Journal of Anatomy 174, 303-315CrossRefGoogle ScholarPubMed
58Sutovsky, P., Navara, C.S. and Schatten, G. (1996) Fate of the sperm mitochondria, and the incorporation, conversion, and disassembly of the sperm tail structures during bovine fertilization. Biology of Reproduction 55, 1195-1205CrossRefGoogle ScholarPubMed
59Sutovsky, P. et al. (2003) Interactions of sperm perinuclear theca with the oocyte: implications for oocyte activation, anti-polyspermy defense, and assisted reproduction. Microscopy Research and Technique 61, 362-378CrossRefGoogle ScholarPubMed
60Sutovsky, P. et al. (1997) The removal of the sperm perinuclear theca and its association with the bovine oocyte surface during fertilization. Developmental Biology 188, 75-84CrossRefGoogle ScholarPubMed
61Phillips, D.M. and Shalgi, R. (1982) Sperm penetration into rat ova fertilized in vivo. Journal of Experimental Zoology 221, 373-378CrossRefGoogle ScholarPubMed
62Thompson, R.S., Smith, D.M. and Zamboni, L. (1974) Fertilization of mouse ova in vitro: an electron microscopic study. Fertility and Sterility 25, 222-249CrossRefGoogle ScholarPubMed
63McAvey, B.A. et al. (2002) Involvement of calcium signaling and the actin cytoskeleton in the membrane block to polyspermy in mouse eggs. Biology of Reproduction 67, 1342-1352CrossRefGoogle ScholarPubMed
64Terada, Y., Simerly, C. and Schatten, G. (2000) Microfilament stabilization by jasplakinolide arrests oocyte maturation, cortical granule exocytosis, sperm incorporation cone resorption, and cell-cycle progression, but not DNA replication, during fertilization in mice. Molecular Reproduction and Development 56, 89-983.0.CO;2-I>CrossRefGoogle Scholar
65Wolf, J.P. et al. (1995) High levels of sperm-associated antibodies impair human spermoolemma interaction after subzonal insemination. Fertility and Sterility 63, 584-590CrossRefGoogle ScholarPubMed
66Wolf, J.P. et al. (1995) Influence of sperm movement parameters on human sperm-oolemma fusion. Journal of Reproduction and Fertility 105, 185-192CrossRefGoogle ScholarPubMed
67Eliyahu, E. et al. (2006) Association between myristoylated alanin-rich C kinase substrate (MARCKS) translocation and cortical granule exocytosis in rat eggs. Reproduction 131, 221-231CrossRefGoogle ScholarPubMed
68Yi, Y.J. et al. (2007) Ubiquitin C-terminal hydrolase-activity is involved in sperm acrosomal function and anti-polyspermy defense during porcine fertilization. Biology of Reproduction 77, 780-793CrossRefGoogle ScholarPubMed
69Susor, A. et al. (2007) Proteomic analysis of porcine oocytes during in vitro maturation reveals essential role for the ubiquitin C-terminal hydrolase-L1. Reproduction 134, 559-568CrossRefGoogle ScholarPubMed
70Sekiguchi, S. et al. (2006) Localization of ubiquitin C-terminal hydrolase L1 in mouse ova and its function in the plasma membrane to block polyspermy. American Journal of Pathology 169, 1722-1729CrossRefGoogle ScholarPubMed
71Komada, M. (2008) Controlling receptor downregulation by ubiquitination and deubiquitination. Current Drug Discovery Technologies 5, 78-84CrossRefGoogle ScholarPubMed
72Glickman, M.H. and Ciechanover, A. (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiological Reviews 82, 373-428CrossRefGoogle ScholarPubMed
73Longo, F.J. et al. (1986) Correlative ultrastructural and electrophysiological studies of sperm-egg interactions of the sea urchin, Lytechinus variegatus. Developmental Biology 118, 155-166CrossRefGoogle ScholarPubMed
74McCulloh, D.H., Rexroad, C.E. Jr and Levitan, H. (1983) Insemination of rabbit eggs is associated with slow depolarization and repetitive diphasic membrane potentials. Developmental Biology 95, 372-377CrossRefGoogle ScholarPubMed
75Jaffe, L.A., Sharp, A.P. and Wolf, D.P. (1983) Absence of an electrical polyspermy block in the mouse. Developmental Biology 96, 317-323CrossRefGoogle ScholarPubMed
76Sun, Q.Y. (2003) Cellular and molecular mechanisms leading to cortical reaction and polyspermy block in mammalian eggs. Microscopy Research and Technique 61, 342-348CrossRefGoogle ScholarPubMed
77Hayasaka, S. et al. (2007) Positive expression of the immunoglobulin superfamily protein IZUMO on human sperm of severely infertile male patients. Fertility and Sterility 88, 214-216CrossRefGoogle ScholarPubMed
78Wang, D.G. et al. (2008) Investigation of recombinant mouse sperm protein izumo as a potential immunocontraceptive antigen. American Journal of Reproductive Immunology 59, 225-234CrossRefGoogle ScholarPubMed
79Naz, R.K. (2008) Immunocontraceptive effect of Izumo and enhancement by combination vaccination. Molecular Reproduction and Development 75, 336-344CrossRefGoogle ScholarPubMed
80Naz, R. and Aleem, A. (2007) Effect of immunization with six sperm peptide vaccines on fertility of female mice. Society of Reproduction and Fertility Supplement 63, 455-464Google ScholarPubMed
81Prather, R.S. (2007) Nuclear remodeling and nuclear reprogramming for making transgenic pigs by nuclear transfer. Advances in Experimental Medicine and Biology 591, 1-13CrossRefGoogle ScholarPubMed
82Oren-Suissa, M. and Podbilewicz, B. (2007) Cell fusion during development. Trends in Cell Biology 17, 537-546CrossRefGoogle ScholarPubMed
83Harrison, S.C. (2008) Viral membrane fusion. Nature Structural and Molecular Biology 15, 690-698CrossRefGoogle ScholarPubMed
84Rizo, J. and Rosenmund, C. (2008) Synaptic vesicle fusion. Nature Structural and Molecular Biology 15, 665-674CrossRefGoogle ScholarPubMed
85Nilsson, B.O. et al. (1999) Expression of envelope proteins of endogeneous C-type retrovirus on the surface of mouse and human oocytes at fertilization. Virus Genes 18, 115-120CrossRefGoogle ScholarPubMed
86Ramalho-Santos, J. et al. (2000) SNAREs in mammalian sperm: possible implications for fertilization. Developmental Biology 223, 54-69CrossRefGoogle ScholarPubMed
87Doherty, K.R. et al. (2005) Normal myoblast fusion requires myoferlin. Development 132, 5565-5575CrossRefGoogle ScholarPubMed
88Washington, N.L. and Ward, S. (2006) FER-1 regulates Ca2+-mediated membrane fusion during C. elegans spermatogenesis. Journal of Cell Science 119, 2552-2562CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

Recent review articles on sperm–oolemma fusion:

Websites with useful information on fertilisation mechanisms in animals:

Primakoff, P. and Myles, D.G. (2007) Cell-cell membrane fusion during mammalian fertilization. FEBS Letters 581, 2174-2180CrossRefGoogle ScholarPubMed
Inoue, N. et al. (2007) Sperm-egg interaction and gene manipulated animals. Society of Reproduction and Fertility Supplement 65, 363-371Google ScholarPubMed
Vjugina, U. and Evans, J.P. (2008) New insights into the molecular basis of mammalian sperm-egg membrane interactions. Frontiers in Bioscience 13, 462-476CrossRefGoogle ScholarPubMed
Suarez, S.S. and Pacey, A.A. (2006) Sperm transport in the female reproductive tract. Human Reproduction Update 12, 23-37CrossRefGoogle ScholarPubMed
http://www.stanford.edu/group/Urchin/path.html (Sea Urchin Embryology, Stanford University)Google Scholar
http://8e.devbio.com/chapter.php?ch=7 (DevBio: Companion to Developmental Biology by S. Gilbert)Google Scholar
http://zygote.swarthmore.edu/chap4.html (Zygote, a virtual library of developmental biology)Google Scholar
Primakoff, P. and Myles, D.G. (2007) Cell-cell membrane fusion during mammalian fertilization. FEBS Letters 581, 2174-2180CrossRefGoogle ScholarPubMed
Inoue, N. et al. (2007) Sperm-egg interaction and gene manipulated animals. Society of Reproduction and Fertility Supplement 65, 363-371Google ScholarPubMed
Vjugina, U. and Evans, J.P. (2008) New insights into the molecular basis of mammalian sperm-egg membrane interactions. Frontiers in Bioscience 13, 462-476CrossRefGoogle ScholarPubMed
Suarez, S.S. and Pacey, A.A. (2006) Sperm transport in the female reproductive tract. Human Reproduction Update 12, 23-37CrossRefGoogle ScholarPubMed
http://www.stanford.edu/group/Urchin/path.html (Sea Urchin Embryology, Stanford University)Google Scholar
http://8e.devbio.com/chapter.php?ch=7 (DevBio: Companion to Developmental Biology by S. Gilbert)Google Scholar
http://zygote.swarthmore.edu/chap4.html (Zygote, a virtual library of developmental biology)Google Scholar