Inhibition of human sperm-zona-free hamster oocyte binding and penetrationby protein C inhibitor

Protein C inhibitor is a heparin-dependent serine protease inhibitor presen t in plasma at about 0.08 mu mol l(-1). Protein C inhibitor inhibits activa ted protein C and other coagulation factors. Previously, we described the p resence of high protein C inhibitor levels in human semen (3.1 mu mol l(-1) ) and showed potential roles of the inhibitor in human reproduction. Here, we show that protein C inhibitor is present in an active form in follicular fluid at about 0.1 mu mol l(-1) and that purified, functionally active hum an plasma-derived and inactive, semen-derived protein C inhibitor and a syn thetic peptide derived from its sequence inhibited both binding and penetra tion of zona-free hamster oocytes by human sperm. The binding inhibition by protein C inhibitor was dose dependent, with 50% inhibition at 0.037 mu mo l l(-1) inhibitor (45+/-17 sperm per egg versus 90+/-23 in control experime nts). The inhibitor also blocked in a dose-dependent manner the penetration of zona-free hamster eggs by human sperm (20+/-7% fertilized eggs at 0.1 m u mol l(-1) protein C inhibitor versus 55+/-10% in control experiments). Po lyclonal antiprotein C inhibitor or antipeptide antibodies partially abolis hed the effect of protein C inhibitor and peptide on the inhibition of the binding and penetration of zona-free hamster oocytes by human sperm. The ef fect of the protein C inhibitor was not dependent on its antiprotease activ ity since purified semen-derived protein C inhibitor which did not have ant iprotease activity gave comparable results. We conclude that protein C inhi bitor may be involved in human reproduction at several steps, including the fertilization process.