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Evolving paradigms in gamete recognition and induction of sperm acrosome exocytosis during mice and human fertilization

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • M.A. Avella
  • B. Baibakov
  • J. Dean


The recent observation that human sperm bind to the mouse zona pellucida only when huZP2 replaces the endogenous mouse protein contradicts long-standing models of ZP3 acting as the primary mediator of gametes recognition and inducer of sperm acrosome exocytosis. We now establish loss-of-function assays in transgenic mice that express huZP4 to supplement the structural integrity of the zona matrix. We document that human and mouse sperm do not bind to a zona pellucida lacking huZP2 and moZP2, respectively, and female mice are sterile. Using chimeric human-mouse ZP2 proteins expressed in transgenic mice, we localize the sperm binding domain to the N-terminus. Sperm from transgenic mice in which nuclear protamines are tagged with EGFP and soluble mCherry is released upon acrosome exocytosis were imaged by time-lapse microscopy. Only acrosome-intact sperm bind to the surface of the zona pellucida and only acrosome-reacted sperm are present in the perivitelline space after penetration of the zona pellucida. Intriguingly, in the absence of ZP1, a looser zona matrix is formed to which acrosome-intact sperm bind and penetrate, but remain acrosome-intact. We conclude that the N-terminus of ZP2 is the ligand for gamete recognition and acrosome exocytosis is induced by the zona matrix during sperm penetration.

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