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

Protein C inhibitor is a heparin-dependent serine protease inhibitor present in plasma at about 0.08 mu mol l(-1). Protein C inhibitor inhibits activated protein C and other coagulation factors. Previously, we described the presence 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 human plasma-derived and inactive, semen-derived protein C inhibitor and a synthetic peptide derived from its sequence inhibited both binding and penetration 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 mol l(-1) inhibitor (45+/-17 sperm per egg versus 90+/-23 in control experiments). 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 mu mol l(-1) protein C inhibitor versus 55+/-10% in control experiments). Polyclonal antiprotein C inhibitor or antipeptide antibodies partially abolished 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 effect of the protein C inhibitor was not dependent on its antiprotease activity since purified semen-derived protein C inhibitor which did not have antiprotease activity gave comparable results. We conclude that protein C inhibitor may be involved in human reproduction at several steps, including the fertilization process.