Model of gamete recognition on the surface of the zona pellucida. The mouse zona pellucida (aquamarine) is composed of ZP1, ZP2, and ZP3, and surrounds ovulated eggs and early embryos. Sperm, capacitated by passage through the female reproductive tract, bind on the surface of the zona pellucida to an N-terminal domain of ZP2 in unfertilized eggs. After sperm acrosome exocytosis and penetration of the zona matrix, gametes fuse at fertilization and activate the egg. This triggers egg cortical granule migration and fusion with the plasma membrane, which releases ovastacin, a zinc metalloendoprotease that cleaves ZP2 at ¹⁶⁶LA↓DE¹⁶⁹. The immediate postfertilization block to polyspermy prevents additional sperm from fusing with eggs or penetrating through the zona pellucida matrix. The most definitive block is secondary to the proteolytic destruction of the sperm binding domain at the N terminus of ZP2. If sperm do not bind, they will not penetrate nor fuse with the egg’s plasma membrane.