Molecular events that regulate mammalian fertilization

Mammalian fertilization is the net result of a highly programmed sequence of molecular events that collectively result in the union of two radically different looking haploid cells, sperm and egg, to form a diploid zygote. For successful fertilization, sperm cells undergo continuous modifications during their formation in the testis, maturation in the epididymis, and capacitation in the female genital tract. Only capacitated acrosome-intact spermatozoa are capable of binding to the egg's extracellular coat, the zona pellucida (ZP) in a receptor-ligand manner. The species-specific irreversible binding of the opposite gametes elevates intrasperm Ca2+ and triggers a signal transduction cascade that results in the fusion of the sperm plasma membrane and outer acrosomal membrane at multiple sites (i.e., induction of the acrosomal reaction) and the secretion of acrosomal contents. The hydrolytic action of the acrosomal enzymes (i.e., glycohydrolases, proteinases etc.) released at the site of sperm-egg binding along with the hyperactivated beat pattern of the bound spermatozoon, are important factors that regulate its penetration of the ZP and fertilization of the egg. In this article, we intend to discuss data from this and other laboratories that provide useful insights into biology underlying sperm development in the testis, maturation in the epididymis, capacitation in the female genital tract, sperm-egg interaction, and induction of the acrosome reaction (AR) before the acrosome reacted sperm can fertilize an egg. Our intention is also to discuss how Ca2+ signaling cascades regulate sperm functions and male fertility. Finally, we will discuss sperm molecules that are under intensive research to regulate male fertility.