Mammalian eggs are surrounded by a zona pellucida (ZP) that regulates egg-sperm teractions during fertilization. The ZP consists of long filaments composed of two glycoproteins, ZP2 and ZP3, that are crosslinked by a third glycoprotein, ZP1. The presence of both ZP2 and ZP3 is essential for assembling a ZP around growing oocytes, as well as for fertility of females. Acrosome-intact sperm recognize and bind to O-linked oligosaccharides linked to Ser residues at the sperm combining-site of ZP3. Structural differences in oligosaccharides on ZP3 from different species may account for whether or not sperm are able to bind to the ZP. Bound sperm undergo the acrosome reaction, penetrate the ZP, and can then fuse with egg plasma membrane. Following fertilization, sperm are unable to bind to either ZP3 or the ZP of one-cell embryos.