Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs

Tracy L. Rankin, Jenell S. Coleman, Olga Epifano, Tanya Hoodbhoy, Scott G. Turner, Philip E. Castle, Eric Lee, Robert Gore-Langton, Jurrien Dean

Research output: Contribution to journalArticle

133 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)33-43
Number of pages11
JournalDevelopmental cell
Volume5
Issue number1
DOIs
StatePublished - Jul 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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    Rankin, T. L., Coleman, J. S., Epifano, O., Hoodbhoy, T., Turner, S. G., Castle, P. E., Lee, E., Gore-Langton, R., & Dean, J. (2003). Fertility and taxon-specific sperm binding persist after replacement of mouse sperm receptors with human homologs. Developmental cell, 5(1), 33-43. https://doi.org/10.1016/S1534-5807(03)00195-3