Human sperm activation during capacitation and acrosome reaction: role of calcium, protein phosphorylation and lipid remodelling pathways

Abstract

Two processes, namely capacitation and acrosome reaction, are of fundamental importance in the fertilization of oocyte by spermatozoon. Physiologically occurring in the female genital tract, capacitation is a complex process, which renders the sperm cell capable for specific interaction with the oocyte. During capacitation, modification of membrane characteristics, enzyme activity and motility property of spermatozoa render these cells responsive to stimuli that induce acrosome reaction prior to fertilization. Physiological acrosome reaction occurs upon interaction of the spermatozoon with the zona pellucida protein ZP3. This is followed by liberation of several acrosomal enzymes and other constituents that facilitate penetration of the zona and exposes molecules on the sperm equatorial segment that allows fusion of sperm membrane with the oolemma. The molecular mechanisms and the signal transduction pathways mediating the processes of capacitation and acrosome reaction are only partially defined, and appear to involve modifications of intracellular calcium and other ions, lipid transfer and phospholipid remodelling in sperm plasma membrane as well as changes in protein phosphorylation. The human and mouse sperm receptor for ZP3 has been recently sequenced and cloned. This receptor exhibits sequence homology with proto-oncogenes that mediate proliferation and differentiation in somatic cells. This review summarizes the main signal transduction pathways involved in capacitation and acrosome reaction.