A molecular membrane model of sperm capacitation and the acrosome reaction of mammalian spermatozoa

Abstract

The abundance of data pertaining to the metabolism of lipids in relation to mammalian fertilization has warranted an effort to assemble a molecular membrane model for the comprehensive visualization of the biochemical events involved in sperm capacitation and the acrosome reaction. Derived both from earlier models as well as from current concepts, our membrane model depicts a lipid bilayer assembly of space-filling molecular models of sterols and phospholipids in dynamic equilibrium with peripheral and integral membrane proteins. A novel feature is the possibility of visualizing individual lipid molecules such as phosphatidylcholine, phosphatidylethanolamine, lysophospholipids, fatty acids, and free or esterified cholesterol. The model illustrates enzymatic reactions which are believed to regulate the permeability and integrity of the plasma membrane overlying the acrosome during interactions between the male gamete and capacitation factors present in fluids of the female genital tract. The use of radioactive lipids as molecular probes for monitoring the metabolism of cholesterol and phosphatidylcholine revealed the presence of 1) steroid sulfatase in hamster cumulus cells, 2) lecithin: cholesterol acyltransferase in human follicular fluid, 3) phospholipase A*, and 4) lysophospholipase in human spermatozoa. These enzymatic reactions can be integrated into a pathway that provides a link between the concepts of lysophospholipid accumulation in the sperm membranes and alteration of the cholesterol/phospholipid ratio as factors involved in the preparation of the membranes for the acrosome reaction. Capacitation is viewed as a reversible phenomenon which, upon completion, results in a decrease in negative surface charge, an efflux of membrane cholesterol, and an influx of calcium between the plasma and outer acrosomal membranes. Triggered by the entry of calcium, the acrosome reaction involves phospholipase A2 activation followed by a transient accumulation of unsaturated fatty acids and lysophospholipids implicated in membrane fusion which occurs during the formation of membrane vesicles in spermatozoa undergoing the acrosome reaction.

Semen Analysis at the Turn of the Century: An Evaluation of Potential Uses of New Sperm Function Assays

“…Sperm capacitation includes an influx of calcium ions, efflux hydrogen ions, and extensive membrane remodeling to a less stable, more fluid membrane status [38]. Capacitation is necessary for sperm to undergo acrosome reaction.…”

Suppression of progesterone-enhanced hyperactivation in hamster spermatozoa by estrogen

“…Albumin promotes capacitation by removing cholesterol from the sperm plasma membrane (Langlais & Roberts 1985). Calcium and bicarbonate are involved in several intracellular signals such as the stimulation of adenylate cyclase, production of cAMP, and protein phosphorylation (Okamura et al 1985, Ho & Suarez 2001, Ho et al 2002.…”

Capacitation, acrosome function and chromatin structure in stallion sperm

“…The most important aspects of capacitation are the changes that enable a sperm to recognize the ZP and undergo the AR in response to ZP-binding; these changes include the facilitation of calcium entry into the cell (Baldi et al, 1991;Okamura et al, 1993;Parrish et al, 1999), increased intracellular calcium and cAMP levels (Visconti and Kopf, 1998;Florman et al, 1989;Visconti et al, 1990), increased membrane fluidity secondary to alterations in lipid composition and architecture (Bearer and Friend, 1982;Langlais and Roberts, 1985;Harrison et al, 1996;Flesch and Gadella, 2000;Harrison and Gadella, 2005) and changes in metabolic activity leading to the acquisition of hypermotility (Yanagimachi, 1994;Nassar et al, 1999). Once capacitated, a sperm cell can bind to the ZP and respond to this binding by undergoing the AR, an exocytotic event that is instrumental to ZP-penetration and subsequent fusion of the sperm plasma membrane with the oolemma.…”