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 mumol 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 mumol 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 mumol 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 mumol 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 mumol 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.
España
F
F
Research Center, La Fe University Hospital, Valencia, Spain.
Sánchez-Cuenca
J
J
Fernández
P J
PJ
Gilabert
J
J
Romeu
A
A
Estellés
A
A
Royo
M
M
Muller
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D018046:Protein C Inhibitor / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013084:Sperm-Ovum Interactions / Q000187:drug effects* / Q000502:physiology; D015044:Zona Pellucida / Q000502:physiology
D010446:Peptide Fragments; D018046:Protein C Inhibitor