title: Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs.
abstract: The zona pellucida surrounding ovulated mouse eggs contains three glycoproteins, two of which (ZP2 and ZP3) are reported sperm receptors. After fertilization, the zona pellucida is modified ad minimus by cleavage of ZP2, and sperm no longer bind. Crosstaxa sperm binding is limited among mammals, and human sperm do not bind to mouse eggs. Using transgenesis to replace mouse ZP2 and/or ZP3 with human homologs, mouse lines with human-mouse chimeric zonae pellucidae have been established. Unexpectedly, mouse, but not human, sperm bind to huZP2 and huZP2/huZP3 rescue eggs, eggs fertilized in vitro with mouse sperm progress to two-cell embryos, and rescue mice are fertile. Also unanticipated, human ZP2 remains uncleaved after fertilization, and mouse sperm continue to bind early rescue embryos. These observations are consistent with a model in which the supramolecular structure of the zona pellucida necessary for sperm binding is modulated by the cleavage status of ZP2.
authors.affiliation: Laboratory of Cellular and Developmental Biology, NIDDK, Suburban Hospital, 20892, Bethesda, MD, USA
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Rankin
authors.forename: Jenell S
authors.initials: JS
authors.lastname: Coleman
authors.forename: Olga
authors.initials: O
authors.lastname: Epifano
authors.forename: Tanya
authors.initials: T
authors.lastname: Hoodbhoy
authors.forename: Scott G
authors.initials: SG
authors.lastname: Turner
authors.forename: Philip E
authors.initials: PE
authors.lastname: Castle
authors.forename: Eric
authors.initials: E
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Gore-Langton
authors.forename: Jurrien
authors.initials: J
authors.lastname: Dean
mesh_terms: D000818:Animals; D002460:Cell Line; D002678:Chimera; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000235:genetics*; D005307:Fertilization in Vitro; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013045:Species Specificity; D013094:Spermatozoa / Q000378:metabolism*; D019076:Transgenes; D015044:Zona Pellucida / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
chemical_list: D004527:Egg Proteins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C000606515:ZP2 protein, human; C000606517:ZP3 protein, human; D000072216:Zona Pellucida Glycoproteins; C000606520:Zp2 protein, mouse; C000606521:Zp3 protein, mouse