{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T01:06:57Z","timestamp":1791767217945,"version":"4.3.4"},"reference-count":123,"publisher":"Rockefeller University Press","issue":"10","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2022,4,4]],"date-time":"2022-04-04T00:00:00Z","timestamp":1649030400000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-153281"],"award-info":[{"award-number":["PJT-153281"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007189","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021716","name":"Universit\u00e9 de Paris","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100021716","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale pour la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE18-0005-02"],"award-info":[{"award-number":["ANR-17-CE18-0005-02"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-024197"],"award-info":[{"award-number":["INV-024197"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Frontiers in Research Fund","award":["NFRFE-2019-00230"],"award-info":[{"award-number":["NFRFE-2019-00230"]}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10,4]]},"abstract":"<jats:p>Fertilization is defined as the union of two gametes. During fertilization, sperm and egg fuse to form a diploid zygote to initiate prenatal development. In mammals, fertilization involves multiple ordered steps, including the acrosome reaction, zona pellucida penetration, sperm\u2013egg attachment, and membrane fusion. Given the success of in vitro fertilization, one would think that the mechanisms of fertilization are understood; however, the precise details for many of the steps in fertilization remain a mystery. Recent studies using genetic knockout mouse models and structural biology are providing valuable insight into the molecular basis of sperm\u2013egg attachment and fusion. Here, we review the cell biology of fertilization, specifically summarizing data from recent structural and functional studies that provide insights into the interactions involved in human gamete attachment and fusion.<\/jats:p>","DOI":"10.1083\/jcb.202102146","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T02:22:00Z","timestamp":1629166920000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":74,"title":["The cell biology of fertilization: Gamete attachment and fusion"],"prefix":"10.1083","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0005-8566","authenticated-orcid":true,"given":"Karen K.","family":"Siu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9398-2941","authenticated-orcid":true,"given":"Vitor Hugo B.","family":"Serr\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9724-3831","authenticated-orcid":true,"given":"Ahmed","family":"Ziyyat","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, Institut Cochin, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Centre National de la Recherche Scientifique, Paris, France 2"},{"name":"Service d\u2019Histologie, d\u2019Embryologie, Biologie de la Reproduction, Assistance Publique - H\u00f4pitaux de Paris, H\u00f4pital Cochin, Paris, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2172-6586","authenticated-orcid":true,"given":"Jeffrey E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathobiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"2023072407324074200_bib1","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1172\/JCI33873","article-title":"As the world grows: contraception in the 21st century","volume":"118","author":"Aitken","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2023072407324074200_bib2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.mce.2016.03.039","article-title":"The spatiotemporal hormonal orchestration of human folliculogenesis, early embryogenesis and blastocyst implantation","volume":"430","author":"Atwood","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072407324074200_bib3","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/170326a0","article-title":"The capacitation of the mammalian sperm","volume":"170","author":"Austin","year":"1952","journal-title":"Nature."},{"key":"2023072407324074200_bib4","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature18595","article-title":"Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex","volume":"534","author":"Aydin","year":"2016","journal-title":"Nature."},{"key":"2023072407324074200_bib5","doi-asserted-by":"publisher","first-page":"5335","DOI":"10.1038\/s41598-020-62091-y","article-title":"Sperm SPACA6 protein is required for mammalian Sperm-Egg Adhesion\/Fusion","volume":"10","author":"Barbaux","year":"2020","journal-title":"Sci. Rep."},{"key":"2023072407324074200_bib6","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1021\/pr100745u","article-title":"Proteomic analysis of seminal plasma from normal volunteers and post-vasectomy patients identifies over 2000 proteins and candidate biomarkers of the urogenital system","volume":"10","author":"Batruch","year":"2011","journal-title":"J. Proteome Res."},{"key":"2023072407324074200_bib7","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1152\/ajplegacy.1962.202.1.179","article-title":"Removal of decapacitation factor from seminal plasma by high-speed centrifugation","volume":"202","author":"Bedford","year":"1962","journal-title":"Am. J. Physiol."},{"key":"2023072407324074200_bib8","first-page":"199","article-title":"The maturation of spermatozoa in the human epididymis","volume":"18","author":"Bedford","year":"1973","journal-title":"J. Reprod. Fertil. Suppl."},{"key":"2023072407324074200_bib10","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2014.0101","article-title":"Cross-species fertilization: the hamster egg receptor, Juno, binds the human sperm ligand, Izumo1","volume":"370","author":"Bianchi","year":"2015","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2023072407324074200_bib11","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/nature13203","article-title":"Juno is the egg Izumo receptor and is essential for mammalian fertilization","volume":"508","author":"Bianchi","year":"2014","journal-title":"Nature."},{"key":"2023072407324074200_bib12","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/S0022-2836(84)71582-8","article-title":"The immunoglobulin fold. Structural classification, sequence patterns and common core","volume":"242","author":"Bork","year":"1994","journal-title":"J. Mol. Biol."},{"key":"2023072407324074200_bib13","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1083\/jcb.201112094","article-title":"Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy","volume":"197","author":"Burkart","year":"2012","journal-title":"J. Cell Biol."},{"key":"2023072407324074200_bib14","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/mrd.20726","article-title":"Relevance of glycosylation of human zona pellucida glycoproteins for their binding to capacitated human spermatozoa and subsequent induction of acrosomal exocytosis","volume":"75","author":"Chakravarty","year":"2008","journal-title":"Mol. Reprod. Dev."},{"key":"2023072407324074200_bib15","doi-asserted-by":"publisher","first-page":"3732","DOI":"10.1242\/dev.111534","article-title":"Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization","volume":"141","author":"Chalbi","year":"2014","journal-title":"Development."},{"key":"2023072407324074200_bib16","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/168697b0","article-title":"Fertilizing capacity of spermatozoa deposited into the fallopian tubes","volume":"168","author":"Chang","year":"1951","journal-title":"Nature."},{"key":"2023072407324074200_bib17","doi-asserted-by":"publisher","first-page":"3641","DOI":"10.1242\/jcs.154906","article-title":"Tetraspanins at a glance","volume":"127","author":"Charrin","year":"2014","journal-title":"J. Cell Sci."},{"key":"2023072407324074200_bib18","doi-asserted-by":"publisher","first-page":"11830","DOI":"10.1073\/pnas.96.21.11830","article-title":"Role of the integrin-associated protein CD9 in binding between sperm ADAM 2 and the egg integrin alpha6beta1: implications for murine fertilization","volume":"96","author":"Chen","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib19","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1126\/science.289.5479.625","article-title":"Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor","volume":"289","author":"Chen","year":"2000","journal-title":"Science."},{"key":"2023072407324074200_bib20","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1146\/annurev.biochem.72.121801.161504","article-title":"Protein-lipid interplay in fusion and fission of biological membranes","volume":"72","author":"Chernomordik","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"2023072407324074200_bib21","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.cell.2005.10.015","article-title":"Membrane hemifusion: crossing a chasm in two leaps","volume":"123","author":"Chernomordik","year":"2005","journal-title":"Cell."},{"key":"2023072407324074200_bib22","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1016\/j.bbrc.2014.06.051","article-title":"A role for carbohydrate recognition in mammalian sperm-egg binding","volume":"450","author":"Clark","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2023072407324074200_bib23","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1152\/physrev.1972.52.1.198","article-title":"Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal","volume":"52","author":"Clermont","year":"1972","journal-title":"Physiol. Rev."},{"key":"2023072407324074200_bib24","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1093\/humupd\/dmn055","article-title":"New insights into epididymal biology and function","volume":"15","author":"Cornwall","year":"2009","journal-title":"Hum. Reprod. Update."},{"key":"2023072407324074200_bib25","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1530\/jrf.0.0800619","article-title":"Visualization of pig sperm chromosomes by in-vitro penetration of zona-free hamster ova","volume":"80","author":"Creighton","year":"1987","journal-title":"J. Reprod. Fertil."},{"key":"2023072407324074200_bib26","doi-asserted-by":"publisher","first-page":"6036","DOI":"10.1039\/C8NR07269H","article-title":"Nanoscale organization of tetraspanins during HIV-1 budding by correlative dSTORM\/AFM","volume":"11","author":"Dahmane","year":"2019","journal-title":"Nanoscale."},{"key":"2023072407324074200_bib27","doi-asserted-by":"publisher","DOI":"10.3390\/cells9041002","article-title":"A Comparative Analysis of Oocyte Development in Mammals","volume":"9","author":"Dalbies-Tran","year":"2020","journal-title":"Cells."},{"key":"2023072407324074200_bib28","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1097\/GCO.0b013e32835faae5","article-title":"Reproductive outcomes in patients with male infertility because of Klinefelter\u2019s syndrome, Kartagener\u2019s syndrome, round-head sperm, dysplasia fibrous sheath, and \u2018stump\u2019 tail sperm: an updated literature review","volume":"25","author":"D\u00e1vila Garza","year":"2013","journal-title":"Curr. Opin. Obstet. Gynecol."},{"key":"2023072407324074200_bib29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030323","article-title":"Dynamics of SNARE assembly and disassembly during sperm acrosomal exocytosis","volume":"3","author":"De Blas","year":"2005","journal-title":"PLoS Biol."},{"key":"2023072407324074200_bib30","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1210\/er.2009-0012","article-title":"The mammalian ovary from genesis to revelation","volume":"30","author":"Edson","year":"2009","journal-title":"Endocr. Rev."},{"key":"2023072407324074200_bib31","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.devcel.2006.03.011","article-title":"A role for sperm surface protein disulfide isomerase activity in gamete fusion: evidence for the participation of ERp57","volume":"10","author":"Ellerman","year":"2006","journal-title":"Dev. Cell."},{"key":"2023072407324074200_bib32","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1002\/mrd.21092","article-title":"Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm","volume":"76","author":"Ellerman","year":"2009","journal-title":"Mol. Reprod. Dev."},{"key":"2023072407324074200_bib33","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.cell.2017.01.024","article-title":"The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein","volume":"168","author":"F\u00e9dry","year":"2017","journal-title":"Cell."},{"key":"2023072407324074200_bib34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/biolre\/iox065","article-title":"Subfertility in bulls carrying a nonsense mutation in transmembrane protein 95 is due to failure to interact with the oocyte vestments","volume":"97","author":"Fernandez-Fuertes","year":"2017","journal-title":"Biol. Reprod."},{"key":"2023072407324074200_bib35","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.110953","article-title":"Ca2+ signaling in mammalian spermatozoa","volume":"516","author":"Finkelstein","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072407324074200_bib36","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/0012-1606(88)90307-7","article-title":"The regulation of acrosomal exocytosis. I. Sperm capacitation is required for the induction of acrosome reactions by the bovine zona pellucida in vitro","volume":"128","author":"Florman","year":"1988","journal-title":"Dev. Biol."},{"key":"2023072407324074200_bib37","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1538\/expanim.17-0153","article-title":"Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models","volume":"67","author":"Fujihara","year":"2018","journal-title":"Exp. Anim."},{"key":"2023072407324074200_bib38","doi-asserted-by":"publisher","first-page":"9393","DOI":"10.1073\/pnas.1917060117","article-title":"Spermatozoa lacking Fertilization Influencing Membrane Protein (FIMP) fail to fuse with oocytes in mice","volume":"117","author":"Fujihara","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib39","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1111\/rda.12541","article-title":"Signalling Events and Associated Pathways Related to the Mammalian Sperm Capacitation","volume":"50","author":"Gangwar","year":"2015","journal-title":"Reprod. Domest. Anim."},{"key":"2023072407324074200_bib40","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1097\/OGX.0000000000000043","article-title":"Definition and epidemiology of unexplained infertility","volume":"69","author":"Gelbaya","year":"2014","journal-title":"Obstet. Gynecol. Surv."},{"key":"2023072407324074200_bib41","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1071\/RD08158","article-title":"Immunoglobulin superfamily member IgSF8 (EWI-2) and CD9 in fertilisation: evidence of distinct functions for CD9 and a CD9-associated protein in mammalian sperm-egg interaction","volume":"21","author":"Glazar","year":"2009","journal-title":"Reprod. Fertil. Dev."},{"key":"2023072407324074200_bib42","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1210\/edrv-17-2-121","article-title":"Regulation of ovarian follicular development in primates: facts and hypotheses","volume":"17","author":"Gougeon","year":"1996","journal-title":"Endocr. Rev."},{"key":"2023072407324074200_bib43","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.619868","article-title":"Human Zona Pellucida Glycoproteins: Binding Characteristics With Human Spermatozoa and Induction of Acrosome Reaction","volume":"9","author":"Gupta","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"2023072407324074200_bib44","doi-asserted-by":"publisher","first-page":"R100","DOI":"10.1016\/j.cub.2015.12.034","article-title":"Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes","volume":"26","author":"Han","year":"2016","journal-title":"Curr. Biol."},{"key":"2023072407324074200_bib45","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1093\/biolreprod\/6.2.300","article-title":"Penetration of zone-free eggs by spermatozoa of different species","volume":"6","author":"Hanada","year":"1972","journal-title":"Biol. Reprod."},{"key":"2023072407324074200_bib46","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1006\/jmbi.1994.1312","article-title":"Many of the immunoglobulin superfamily domains in cell adhesion molecules and surface receptors belong to a new structural set which is close to that containing variable domains","volume":"238","author":"Harpaz","year":"1994","journal-title":"J. Mol. Biol."},{"key":"2023072407324074200_bib47","doi-asserted-by":"publisher","first-page":"361","DOI":"10.3109\/10425179409010186","article-title":"Cloning and characterization of zona pellucida genes and cDNAs from a variety of mammalian species: the ZPA, ZPB and ZPC gene families","volume":"4","author":"Harris","year":"1994","journal-title":"DNA Seq."},{"key":"2023072407324074200_bib48","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.virol.2015.03.043","article-title":"Viral membrane fusion","volume":"479-480","author":"Harrison","year":"2015","journal-title":"Virology."},{"key":"2023072407324074200_bib49","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1538\/expanim.59.105","article-title":"Transgenic mouse sperm that have green acrosome and red mitochondria allow visualization of sperm and their acrosome reaction in vivo","volume":"59","author":"Hasuwa","year":"2010","journal-title":"Exp. Anim."},{"key":"2023072407324074200_bib50","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1111\/dgd.12653","article-title":"Environmental factors for establishment of the dormant state in oocytes","volume":"62","author":"Hayashi","year":"2020","journal-title":"Dev. Growth Differ."},{"key":"2023072407324074200_bib51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-0-387-09597-4_1","article-title":"Spermatogenesis and cycle of the seminiferous epithelium","volume":"636","author":"Hess","year":"2008","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023072407324074200_bib52","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1095\/biolreprod.116.140400","article-title":"The Behavior and Acrosomal Status of Mouse Spermatozoa In Vitro, and Within the Oviduct During Fertilization after Natural Mating","volume":"95","author":"Hino","year":"2016","journal-title":"Biol. Reprod."},{"key":"2023072407324074200_bib53","article-title":"Physiology, Ovulation","volume-title":"StatPearls.","author":"Holesh","year":"2021"},{"key":"2023072407324074200_bib55","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1016\/j.cell.2019.03.047","article-title":"Dual Sensing of Physiologic pH and Calcium by EFCAB9 Regulates Sperm Motility","volume":"177","author":"Hwang","year":"2019","journal-title":"Cell."},{"key":"2023072407324074200_bib56","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature03362","article-title":"The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs","volume":"434","author":"Inoue","year":"2005","journal-title":"Nature."},{"key":"2023072407324074200_bib57","doi-asserted-by":"publisher","first-page":"20008","DOI":"10.1073\/pnas.1116965108","article-title":"Acrosome-reacted mouse spermatozoa recovered from the perivitelline space can fertilize other eggs","volume":"108","author":"Inoue","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib58","doi-asserted-by":"publisher","first-page":"8858","DOI":"10.1038\/ncomms9858","article-title":"Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm-egg fusion in mice","volume":"6","author":"Inoue","year":"2015","journal-title":"Nat. Commun."},{"key":"2023072407324074200_bib59","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66313","article-title":"Evolutionarily conserved sperm factors, DCST1 and DCST2, are required for gamete fusion","volume":"10","author":"Inoue","year":"2021","journal-title":"eLife."},{"key":"2023072407324074200_bib60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020004","article-title":"Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer","volume":"2","author":"Ishino","year":"2004","journal-title":"PLoS Biol."},{"key":"2023072407324074200_bib61","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s12565-015-0323-9","article-title":"Acrosome markers of human sperm","volume":"91","author":"Ito","year":"2016","journal-title":"Anat. Sci. Int."},{"key":"2023072407324074200_bib62","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155377","article-title":"The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction","volume":"21","author":"James","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2023072407324074200_bib63","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/humrep\/dey340","article-title":"JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation","volume":"34","author":"Jean","year":"2019","journal-title":"Hum. Reprod."},{"key":"2023072407324074200_bib64","doi-asserted-by":"publisher","first-page":"10946","DOI":"10.1073\/pnas.1017400108","article-title":"CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization","volume":"108","author":"J\u00e9gou","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib65","doi-asserted-by":"publisher","first-page":"4892","DOI":"10.1073\/pnas.1018202108","article-title":"Most fertilizing mouse spermatozoa begin their acrosome reaction before contact with the zona pellucida during in vitro fertilization","volume":"108","author":"Jin","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib66","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/73502","article-title":"The gamete fusion process is defective in eggs of Cd9-deficient mice","volume":"24","author":"Kaji","year":"2000","journal-title":"Nat. Genet."},{"key":"2023072407324074200_bib67","doi-asserted-by":"publisher","first-page":"598","DOI":"10.14310\/horm.2002.1623","article-title":"Male contraception: a clinically-oriented review","volume":"14","author":"Kanakis","year":"2015","journal-title":"Hormones (Athens)."},{"key":"2023072407324074200_bib68","doi-asserted-by":"publisher","first-page":"12198","DOI":"10.1038\/ncomms12198","article-title":"Structural and functional insights into IZUMO1 recognition by JUNO in mammalian fertilization","volume":"7","author":"Kato","year":"2016","journal-title":"Nat. Commun."},{"key":"2023072407324074200_bib69","doi-asserted-by":"publisher","DOI":"10.3791\/3881","article-title":"Avidity-based extracellular interaction screening (AVEXIS) for the scalable detection of low-affinity extracellular receptor-ligand interactions","volume":"3881","author":"Kerr","year":"2012","journal-title":"J. Vis. Exp."},{"key":"2023072407324074200_bib70","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/rda.12576","article-title":"Transport, Distribution and Elimination of Mammalian Sperm Following Natural Mating and Insemination","volume":"50","author":"K\u00f6lle","year":"2015","journal-title":"Reprod. Domest. Anim."},{"key":"2023072407324074200_bib71","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.ydbio.2016.02.006","article-title":"Mouse sperm begin to undergo acrosomal exocytosis in the upper isthmus of the oviduct","volume":"411","author":"La Spina","year":"2016","journal-title":"Dev. Biol."},{"key":"2023072407324074200_bib72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53913","article-title":"TMEM95 is a sperm membrane protein essential for mammalian fertilization","volume":"9","author":"Lamas-Toranzo","year":"2020","journal-title":"eLife."},{"key":"2023072407324074200_bib73","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1126\/science.287.5451.319","article-title":"Severely reduced female fertility in CD9-deficient mice","volume":"287","author":"Le Naour","year":"2000","journal-title":"Science."},{"key":"2023072407324074200_bib74","doi-asserted-by":"publisher","first-page":"3980","DOI":"10.1021\/bi952722m","article-title":"Characterization of mouse ZP3-derived glycopeptide, gp55, that exhibits sperm receptor and acrosome reaction-inducing activity in vitro","volume":"35","author":"Litscher","year":"1996","journal-title":"Biochemistry."},{"key":"2023072407324074200_bib75","doi-asserted-by":"publisher","first-page":"337","DOI":"10.14670\/HH-22.337","article-title":"Egg extracellular coat proteins: from fish to mammals","volume":"22","author":"Litscher","year":"2007","journal-title":"Histol. Histopathol."},{"key":"2023072407324074200_bib76","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s00335-013-9491-x","article-title":"A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion","volume":"25","author":"Lorenzetti","year":"2014","journal-title":"Mamm. Genome."},{"key":"2023072407324074200_bib77","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/jemt.20303","article-title":"Oocyte-follicle cell interactions during ovarian follicle development, as seen by high resolution scanning and transmission electron microscopy in humans","volume":"69","author":"Makabe","year":"2006","journal-title":"Microsc. Res. Tech."},{"key":"2023072407324074200_bib78","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1080\/15592294.2019.1646572","article-title":"Epigenetic changes and assisted reproductive technologies","volume":"15","author":"Mani","year":"2020","journal-title":"Epigenetics."},{"key":"2023072407324074200_bib79","doi-asserted-by":"publisher","first-page":"549","DOI":"10.23736\/S0026-4784.18.04274-0","article-title":"Programmed cell death in the human ovary","volume":"70","author":"Marcozzi","year":"2018","journal-title":"Minerva Ginecol."},{"key":"2023072407324074200_bib80","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1126\/science.287.5451.321","article-title":"Requirement of CD9 on the egg plasma membrane for fertilization","volume":"287","author":"Miyado","year":"2000","journal-title":"Science."},{"key":"2023072407324074200_bib81","doi-asserted-by":"publisher","first-page":"14209","DOI":"10.1073\/pnas.0507005102","article-title":"Incorporation of the acrosome into the oocyte during intracytoplasmic sperm injection could be potentially hazardous to embryo development","volume":"102","author":"Morozumi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib82","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/S0014-5793(99)00433-0","article-title":"Real-time observation of acrosomal dispersal from mouse sperm using GFP as a marker protein","volume":"449","author":"Nakanishi","year":"1999","journal-title":"FEBS Lett."},{"key":"2023072407324074200_bib83","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1006\/dbio.2001.0353","article-title":"Alkalinization of acrosome measured by GFP as a pH indicator and its relation to sperm capacitation","volume":"237","author":"Nakanishi","year":"2001","journal-title":"Dev. Biol."},{"key":"2023072407324074200_bib84","doi-asserted-by":"publisher","first-page":"3225","DOI":"10.1016\/j.cub.2015.10.056","article-title":"The Immunoglobulin-like Gene spe-45 Acts during Fertilization in Caenorhabditis elegans like the Mouse Izumo1 Gene","volume":"25","author":"Nishimura","year":"2015","journal-title":"Curr. Biol."},{"key":"2023072407324074200_bib85","doi-asserted-by":"publisher","first-page":"R661","DOI":"10.1016\/j.cub.2016.06.028","article-title":"The structure of sperm Izumo1 reveals unexpected similarities with Plasmodium invasion proteins","volume":"26","author":"Nishimura","year":"2016","journal-title":"Curr. Biol."},{"key":"2023072407324074200_bib86","doi-asserted-by":"publisher","first-page":"11493","DOI":"10.1073\/pnas.1922650117","article-title":"Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice","volume":"117","author":"Noda","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib87","doi-asserted-by":"publisher","first-page":"3259","DOI":"10.3390\/ijms22063259","article-title":"Structure and Function of Ion Channels Regulating Sperm Motility-An Overview","volume":"22","author":"Nowicka-Bauer","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"2023072407324074200_bib88","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nature18596","article-title":"Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization","volume":"534","author":"Ohto","year":"2016","journal-title":"Nature."},{"key":"2023072407324074200_bib89","doi-asserted-by":"publisher","first-page":"646","DOI":"10.4103\/1008-682X.153299","article-title":"Mechanisms of fertilization elucidated by gene-manipulated animals","volume":"17","author":"Okabe","year":"2015","journal-title":"Asian J. Androl."},{"key":"2023072407324074200_bib90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-319-30567-7_1","article-title":"The Acrosome Reaction: A Historical Perspective","volume":"220","author":"Okabe","year":"2016","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"2023072407324074200_bib91","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1002\/1873-3468.13101","article-title":"Beware of memes in the interpretation of your results - lessons from gene-disrupted mice in fertilization research","volume":"592","author":"Okabe","year":"2018","journal-title":"FEBS Lett."},{"key":"2023072407324074200_bib92","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12958-018-0445-8","article-title":"The art of oocyte meiotic arrest regulation","volume":"17","author":"Pan","year":"2019","journal-title":"Reprod. Biol. Endocrinol."},{"key":"2023072407324074200_bib93","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1126\/science.1207438","article-title":"Human sperm binding is mediated by the sialyl-Lewis(x) oligosaccharide on the zona pellucida","volume":"333","author":"Pang","year":"2011","journal-title":"Science."},{"key":"2023072407324074200_bib94","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004044","article-title":"A nonsense mutation in TMEM95 encoding a nondescript transmembrane protein causes idiopathic male subfertility in cattle","volume":"10","author":"Pausch","year":"2014","journal-title":"PLoS Genet."},{"key":"2023072407324074200_bib95","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/35054500","article-title":"Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion","volume":"409","author":"Peters","year":"2001","journal-title":"Nature."},{"key":"2023072407324074200_bib96","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1146\/annurev-cellbio-101512-122422","article-title":"Virus and cell fusion mechanisms","volume":"30","author":"Podbilewicz","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2023072407324074200_bib97","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1093\/jmcb\/mjy005","article-title":"Egg CD9 protein tides correlated with sperm oscillations tune the gamete fusion ability in mammal","volume":"10","author":"Ravaux","year":"2018","journal-title":"J. Mol. Cell Biol."},{"key":"2023072407324074200_bib98","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.semcdb.2006.02.012","article-title":"The molecular players of sperm-egg fusion in mammals","volume":"17","author":"Rubinstein","year":"2006","journal-title":"Semin. Cell Dev. Biol."},{"key":"2023072407324074200_bib99","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.ydbio.2006.12.041","article-title":"Oocyte CD9 is enriched on the microvillar membrane and required for normal microvillar shape and distribution","volume":"304","author":"Runge","year":"2007","journal-title":"Dev. Biol."},{"key":"2023072407324074200_bib100","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/jez.1402090205","article-title":"An ultrastructural study of epididymal mouse spermatozoa binding to zonae pellucidae in vitro: sequential relationship to the acrosome reaction","volume":"209","author":"Saling","year":"1979","journal-title":"J. Exp. Zool."},{"key":"2023072407324074200_bib101","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.devcel.2007.12.008","article-title":"Viral and developmental cell fusion mechanisms: conservation and divergence","volume":"14","author":"Sapir","year":"2008","journal-title":"Dev. Cell."},{"key":"2023072407324074200_bib102","doi-asserted-by":"publisher","first-page":"4985","DOI":"10.1242\/jcs.100867","article-title":"Visualization of the moment of mouse sperm-egg fusion and dynamic localization of IZUMO1","volume":"125","author":"Satouh","year":"2012","journal-title":"J. Cell Sci."},{"key":"2023072407324074200_bib103","doi-asserted-by":"publisher","first-page":"3220","DOI":"10.1016\/j.cub.2015.10.055","article-title":"Forward Genetics Identifies a Requirement for the Izumo-like Immunoglobulin Superfamily spe-45 Gene in Caenorhabditis elegans Fertilization","volume":"25","author":"Singaravelu","year":"2015","journal-title":"Curr. Biol."},{"key":"2023072407324074200_bib104","doi-asserted-by":"publisher","first-page":"21420","DOI":"10.1073\/pnas.1218581109","article-title":"Shape change in the receptor for gliding motility in Plasmodium sporozoites","volume":"109","author":"Song","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072407324074200_bib105","doi-asserted-by":"publisher","first-page":"2741","DOI":"10.1242\/jcs.047225","article-title":"Tssk6 is required for Izumo relocalization and gamete fusion in the mouse","volume":"122","author":"Sosnik","year":"2009","journal-title":"J. Cell Sci."},{"key":"2023072407324074200_bib106","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/978-3-319-30567-7_5","article-title":"Sperm Capacitation and Acrosome Reaction in Mammalian Sperm","volume":"220","author":"Stival","year":"2016","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"2023072407324074200_bib107","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.mce.2008.01.029","article-title":"Zona pellucida components are present in human fetal ovary before follicle formation","volume":"289","author":"T\u00f6rm\u00e4l\u00e4","year":"2008","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072407324074200_bib108","doi-asserted-by":"publisher","first-page":"230","DOI":"10.3389\/fcell.2019.00230","article-title":"Importance of SLC26 Transmembrane Anion Exchangers in Sperm Post-testicular Maturation and Fertilization Potential","volume":"7","author":"Tour\u00e9","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"2023072407324074200_bib109","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1038\/s41467-020-15459-7","article-title":"Structural insights into tetraspanin CD9 function","volume":"11","author":"Umeda","year":"2020","journal-title":"Nat. Commun."},{"key":"2023072407324074200_bib110","doi-asserted-by":"publisher","first-page":"R750","DOI":"10.1016\/j.cub.2020.05.029","article-title":"Virus and eukaryote fusogen superfamilies","volume":"30","author":"Vance","year":"2020","journal-title":"Curr. Biol."},{"key":"2023072407324074200_bib111","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.mce.2013.08.012","article-title":"Role of anti-M\u00fcllerian hormone and bone morphogenetic proteins in the regulation of FSH sensitivity","volume":"382","author":"Visser","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"2023072407324074200_bib112","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/10409230802058320","article-title":"Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme","volume":"43","author":"White","year":"2008","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"2023072407324074200_bib113","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1111\/and.12068","article-title":"Assessment of sperm hyperactivated motility and acrosome reaction can discriminate the use of spermatozoa for conventional in vitro fertilisation or intracytoplasmic sperm injection: preliminary results","volume":"46","author":"Wiser","year":"2014","journal-title":"Andrologia."},{"key":"2023072407324074200_bib114","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1002\/mrd.23180","article-title":"An update of the regulatory factors of sperm migration from the uterus into the oviduct by genetically manipulated mice","volume":"86","author":"Xiong","year":"2019","journal-title":"Mol. Reprod. Dev."},{"key":"2023072407324074200_bib115","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.immuni.2007.04.017","article-title":"Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor","volume":"27","author":"Yamaguchi","year":"2007","journal-title":"Immunity."},{"key":"2023072407324074200_bib116","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1095\/biolreprod.108.074021","article-title":"Disruption of ADAM3 impairs the migration of sperm into oviduct in mouse","volume":"81","author":"Yamaguchi","year":"2009","journal-title":"Biol. Reprod."},{"key":"2023072407324074200_bib117","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/B978-0-12-416022-4.00009-3","article-title":"Spermatogonial stem cell functions in physiological and pathological conditions","volume":"107","author":"Yang","year":"2014","journal-title":"Curr. Top. Dev. Biol."},{"key":"2023072407324074200_bib118","doi-asserted-by":"publisher","first-page":"708","DOI":"10.4103\/1008-682X.156119","article-title":"Phosphorylation of Izumo1 and Its Role in Male Infertility","volume":"17","author":"Young","year":"2015","journal-title":"Asian J. Androl."},{"key":"2023072407324074200_bib119","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.575126","article-title":"Male Decapacitation Factor SPINK3 Blocks Membrane Hyperpolarization and Calcium Entry in Mouse Sperm","volume":"8","author":"Zalazar","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2023072407324074200_bib120","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1007\/s00018-012-0954-0","article-title":"Tetraspanins and cell membrane tubular structures","volume":"69","author":"Zhang","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"2023072407324074200_bib121","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.gene.2015.09.026","article-title":"Identification of novel alternative splicing transcript and expression analysis of bovine TMEM95 gene","volume":"575","author":"Zhang","year":"2016","journal-title":"Gene."},{"key":"2023072407324074200_bib122","doi-asserted-by":"publisher","first-page":"2523","DOI":"10.1038\/s41467-021-22829-2","article-title":"Oocyte-derived microvilli control female fertility by optimizing ovarian follicle selection in mice","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"2023072407324074200_bib123","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1242\/dev.129.8.1995","article-title":"Residues SFQ (173-175) in the large extracellular loop of CD9 are required for gamete fusion","volume":"129","author":"Zhu","year":"2002","journal-title":"Development."},{"key":"2023072407324074200_bib124","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.cell.2016.09.056","article-title":"Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket","volume":"167","author":"Zimmerman","year":"2016","journal-title":"Cell."},{"key":"2023072407324074200_bib125","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1242\/jcs.02730","article-title":"CD9 controls the formation of clusters that contain tetraspanins and the integrin alpha 6 beta 1, which are involved in human and mouse gamete fusion","volume":"119","author":"Ziyyat","year":"2006","journal-title":"J. Cell Sci."}],"container-title":["Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202102146\/1632031\/jcb_202102146.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202102146\/1632031\/jcb_202102146.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T03:33:50Z","timestamp":1690169630000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/220\/10\/e202102146\/212606\/The-cell-biology-of-fertilization-Gamete"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":123,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10,4]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.202102146","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]},"article-number":"e202102146"}}