PROTEIN-C INHIBITOR MAY MODULATE HUMAN SPERM-OOCYTE INTERACTIONS

Protein C inhibitor (PCI) is a heparin-binding plasma si pine protease inhibitor that was originally identified as an inhibitor of activated protein C. PCI has a broad protease specificity, inhibiting several p roteases in hemostasis and fibrinolysis by acting as a suicide substra te. Recently it has been reported that proteases of the reproductive s ystem, such as acrosin, prostate-specific antigen, and tissue kallikre in, can also be effectively inhibited by PCB. However, a direct relati on between PCI and physiological events during fertilization has not y et been established. an attempt was made to monitor and localize the i nhibition of the sperm protease acrosin by PCI. Localization experimen ts for PCI on epididymal spermatozoa showed that PCI is present on the acrosomal cap of human spermatozoa, which demonstrates the early pres ence of PCI in the male reproductive tract. induction of the acrosome reaction in ejaculated human spermatozoa resulted in the disappearance of PCI from the plasma membrane overlying the acrosomal head and the appearance of a strict distribution at the equatorial segment of human spermatozoa, The activity of acrosin In sperm extracts could be effec tively inhibited by PCI, Zona-binding assays showed that active PCI is able to block sperm-egg binding in a concentration-dependent manner. The combination of the potent inhibition of acrosin and sperm-egg bind ing by PCI and the localization studies suggested that PCI may protect spermatozoa against premature acrosome reaction and degradation, ther eby modulating the acrosin activity so that it can coincide with bindi ng to the oocyte.