The Molecular Biology of Fertilization

Monospermic fertilization is essential for the onset of development. One sperm is required, but two are embryonic lethal. A major arbiter of this constricted window of opportunity is the zona pellucida that surrounds ovulated eggs and pre-implantation embryos. Using mouse transgenesis, we document that the N-terminus of ZP2 is necessary and sufficient for sperm binding to the zona matrix, independent of O- or N-glycans. Immediately following fertilization, high concentrations of zinc are released from cortical granules to inhibit forward motility of sperm which prevents passage through the zona matrix. This transient block to zona penetration provides a temporal window for ovastacin, a metalloendopeptidase exocytosed from cortical granule, to complete cleavage of ZP2 which precludes additional sperm binding and ensures monospermic fertilization.