The mammalian zona pellucida is composed of 3 major glycoproteins, ZP1, ZP2, and ZP3. ZP3, the
molecule responsible for the major sperm-receptor activity of the zona, plays a significant role in fertilization. ZP2 is implicated as a secondary sperm receptor that binds sperm only after the induction of the sperm acrosome reaction. Immediately after fertilization, there are 2 major changes that prevent polyspermy: a rapid electrical
depolarization of the egg plasma membrane that blocks additional sperm in the perivitelline space from fusing with the
egg, and biochemical modifications of the zona pellucida. Both ZP2 and ZP3 are modified by the zona
reaction: ZP2 undergoes a proteolytic cleavage and ZP3 loses its ability to induce the acrosome reaction and its sperm
receptor activity.( Wassarman ; Dean et al 1997 ).
The sperm receptor function of the ZP3 molecule plays a key role in the first step of the fertilization process.
Following sperm-oocyte binding, ZP3 triggers the sperm acrosome reaction that releases the protein machinery enabling
a spermatozoon to penetrate the zona pellucida. van Duin et al. (1992) identified a second polymorphic locus encoding zona pellucida
glycoprotein 3. The variation in the second locus consisted of an extra G residue in exon 8, predicted to encode a
truncated protein of 372 amino acids. The frequency of the ZP3-372 allele in Caucasian and Japanese populations was
69 and 21%, respectively. Provided that ZP3-372 mRNA is translated in vivo, corresponding differences in the
ZP3-372 protein levels might have an impact on human zona pellucida composition and function.