Gamete recognition requires ZP2 for sperm binding to the zona pellucida in mice and humans

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIDDK	DEV-1

* FARE Award Winner

Authors

• M A Avella
• B Baibakov
• J Dean

Abstract

Despite the presence of only three glycoproteins in the zona pellucida surrounding ovulated eggs, the identification of the zona ligand for gamete recognition has been controversial. Using loss-of-function assays with eggs from mice lacking ZP1, ZP2 or ZP3, we have documented that ZP1 is not required for mouse sperm binding. However, mice lacking either ZP2 or ZP3 do not form a zona matrix and nothing could be concluded as to their role in gamete recognition. Human sperm are fastidious and do not bind to the mouse zona pellucida. We have established transgenic mice in which the three mouse proteins are replaced with human homologues plus ZP4 that is not expressed in mouse. Both mouse and human sperm bind and penetrate the ‘humanized’ zona. In mice lacking huZP3, no zona matrix is formed. However, mice lacking huZP2 form a matrix composed of huZP1, huZP3 and huZP4. Neither human nor mouse sperm bind to their zonae pellucidae in vitro and the mouse line is sterile. These loss-of-function assays document that ZP2 is essential for gamete recognition and complement gain-of-function assays in mice in which human sperm bind to a ‘humanized’ zona pellucida when huZP2 replaces endogenous moZP2.

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