The multifunctional zona pellucida and mammalian fertilization.

An early step in mammalian fertilization is species-restricted binding of sperm to the oocyte's zona pellucida (ZP), a thick extracellular coat. Sperm bind to the ZP of unfertilized oocytes, but not to the ZP of fertilized oocytes. Shortly after binding to the unfertilized oocyte ZP, sperm undergo the acrosome reaction (AR). Three mouse ZP glycoproteins, called mZP1-3, constitute the mouse oocyte's ZP and participate in the process of fertilization. For example, sperm exposed to unfertilized oocyte mZP3 at nanomolar concentrations are inhibited from binding to oocytes and undergo the AR; mZP1 and mZP2 have no effect. mZP3 from fertilized oocytes has no effect on sperm binding and is unable to induce the AR. These properties of mZP3 strongly suggest that it is a receptor for sperm and inducer of the AR. Mapping of the mZP3 combining-site for sperm suggests that it is located near the C-terminus of the polypeptide, in a region encoded by exon-7 of the mZP3 gene. This region of mZP3 is a site of positive Darwinian selection. When mZP3 exon-7 is fused to the Fc fragment of human IgG and sperm are exposed to the chimeric protein, the sperm are inhibited from binding to oocytes, suggesting that the inhibitory activity of mZP3 is dependent on this region of its polypeptide.