Co‐Expression of Mannose‐Ligand and Non‐Nuclear Progesterone Receptors on Motile Human Sperm Identifies an Acrosome‐Reaction Inducible Subpopulation

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Abstract
PROBLEM: To determine whether surface expression of receptors for progesterone and mannose can be used to identify spermatozoa likely to undergo an acrosome reaction after zona binding and to compare the reactivity of these receptors with naturally occurring sperm head-directed anti-sperm antibodies (ASAs). METHOD: Progesterone binding sites on the surface of fresh and capacitated motile human sperm in relation to acrosome status were visualized using a cell-impermeant progesterone. Free 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 precipitated following passive transfer of serum ASAs were probed with progesterone-horseradish peroxidase. The effects of the same ASAs on ligand binding and on the induced acrosome reaction were examined. RESULTS: The two receptors are located in close proximity on a subset of capacitated motile sperm and are coordinately cleared from the plasma membrane overlying the acrosomal cap prior to exocytosis. The surface appearance of functional binding sites for each ligand, however, is regulated by different mechanisms and the progesterone receptor alone is specifically precipitated by ASAs. Passive transfer of ASAs to capacitated sperm selectively inhibits the progesterone-stimulated acrosome reaction but not the ionomycin-induced acrosome reaction or the ability of sperm to bind mannose ligands. CONCLUSIONS: Sperm from fertile donors incubated under capacitating conditions in vitro can be subdivided into acrosome reaction inducible and noninducible subpopulations on the basis of the co-expression or total absence of these receptors. The combined data indicate that reaction of sperm surface progesterone receptors with ASAs contributes to the acrosome reaction insufficiency observed in anti-sperm immune infertility.