Regulation of membrane stability and the acrosome reaction in mammalian sperm.

Membrane destabilization is an essential step in the process of membrane fusion. In many cell types, exocytotic fusion may occur sporadically at microscopically localized sites on the surface of the cell, making it difficult to study the chemical and physical features of the membrane (or membranes) that promote fusion. In the sperm cell, exocytosis occurs synchronously at a distinct region on the sperm head. This localization of function makes the sperm cell a useful model to investigate the structural features of the bilayers that control membrane fusion. During sperm maturation, the anterior head membranes undergo a well-defined series of chemical, physical, and functional changes that are necessary to produce a fertile gamete. These changes include the addition of highly unsaturated phosphatidylcholine, a decrease in general membrane stability, and an increase in the ability to respond to physiological and pharmacological inducers of exocytosis. Concomitant addition of cholesterol and an actively maintained asymmetric transmembrane phospholipid distribution modulate these effects to stabilize the membrane of the mature sperm for storage. The environment of the female tract provides conditions that promote efflux of cholesterol from the sperm plasma membrane as well as the loss of membrane asymmetry. The cholesterol-poor, lipid-symmetric plasma membrane has a destabilized inner leaflet that facilitates membrane fusion upon binding of the sperm to the appropriate egg coat receptors. We summarize these features in a mechanistic model in which the sperm membrane contains destabilizing components to confer fusogenic potential as well as stabilizing components organized to maximize membrane integrity. This combination prevents premature fusion in the male tract. After deposition in the female tract and removal of the stabilizing components, followed by reorganization of the fusogenic components, the membrane becomes poised to fuse upon receipt of the final biological stimulus.