Fertility and Taxon-Specific Sperm Binding Persist after Replacement of Mouse Sperm Receptors with Human Homologs

• Published in: Developmental cell Vol. 5; no. 1; pp. 33 - 43
• Main Authors: Rankin, Tracy L, Coleman, Jenell S, Epifano, Olga, Hoodbhoy, Tanya, Turner, Scott G, Castle, Philip E, Lee, Eric, Gore-Langton, Robert, Dean, Jurrien
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2003
• Subjects: Animals; Cell Line; Chimera; Egg Proteins - chemistry; Egg Proteins - genetics; Egg Proteins - metabolism; Female; Fertility - genetics; Fertilization in Vitro; Humans; Male; Membrane Glycoproteins - metabolism; Mice; Mice, Knockout; Mice, Transgenic; Models, Biological; Receptors, Cell Surface - metabolism; Species Specificity; Spermatozoa - metabolism; Transgenes; Zona Pellucida - metabolism; Zona Pellucida Glycoproteins
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(03)00195-3

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 hu
ZP2 and hu
ZP2/hu
ZP3 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.