COEXPRESSION OF MANNOSE-LIGAND AND NONNUCLEAR PROGESTERONE RECEPTORS ON MOTILE HUMAN SPERM IDENTIFIES AN ACROSOME-REACTION INDUCIBLE SUBPOPULATION

PROBLEM: To determine whether surface expression of receptors for prog esterone and mannose can be used to identify spermatozoa likely to und ergo an acrosome reaction after zona binding and to compare the reacti vity of these receptors with naturally occurring sperm head-directed a nti-sperm antibodies (ASAs). METHOD: Progesterone binding sites on the surface of fresh and capacitated motile human sperm in relation to ac rosome status were visualized using a cell-impermeant progesterone, Fr ee progesterone and/or mannose ligands were compared for percent sperm binding and ability to induce an acrosome reaction. Western blots of sperm proteins localized to the plasma membrane and surface proteins p recipitated following passive transfer of serum ASAs were probed with progesterone-horseradish peroxidase. The effects of the same ASAs on l igand binding and on the induced acrosome reaction were examined. RESU LTS: The two receptors are located in close proximity on a subset of c apacitated motile sperm and are coordinately cleared from the plasma m embrane overlying the acrosomal cap prior to exocytosis, The surface a ppearance of functional binding sites for each ligand, however, is reg ulated by different mechanisms and the progesterone receptor alone is specifically precipitated by ASAs. Passive transfer of ASAs to capacit ated sperm selectively inhibits the progesterone-stimulated acrosome r eaction but not the ionomycin-induced acrosome reaction or the ability of sperm to bind mannose ligands. CONCLUSIONS: Sperm from fertile don ors incubated under capacitating conditions in vitro can be subdivided into acrosome reaction inducible and noninducible subpopulations on t he basis of the co-expression or total absence of these receptors. The combined data indicate that reaction of sperm surface progesterone re ceptors with ASAs contributes to the acrosome reaction insufficiency o bserved in anti-sperm immune infertility.