The identity of zona pellucida receptor on spermatozoa: An unresolved issue in developmental biology

Mammalian oocytes are surrounded by an acellular zona pellucida (ZP). Fertilization begins when a capacitated spermatozoon binds to the ZP. Defective sperm-ZP interaction is a cause of male infertility and reduced fertilization rates in clinical assisted reproduction treatment. Despite the importance of spermatozoa-ZP binding, the mechanisms and regulation of the interaction are unclear partly due to the failure in the identification of ZP receptor on spermatozoa. Most of the previous studies assumed that the sperm ZP receptor is a single molecular species, and a number of potential candidates had been suggested. Yet none of them can be considered as the sole sperm ZP receptor. Accumulated evidence suggested that the sperm ZP receptor is a dynamic multi-molecular structure requiring coordinated action of different proteins that are assembled into a functional complex during post-testicular maturation and capacitation. The complex components may include carbohydrate-binding, protein-binding and acrosomal matrix proteins which work as a suite to mediate spermatozoa-ZP interaction. This article aims to review the latest insights in the identification of the sperm ZP receptor. Continued investigation of the area will provide considerable understanding of the regulation of fertilization that will be useful for practical application in human contraception and reproductive medicine.