Inhibition of human sperm penetration into zona-free hamster oocytes by proteinase inhibitors.
The potential role of serine proteinase in the penetration of human spermatozoa into denuded (zona-free) hamster oocytes was investigated. Aryl 4-guanidinobenzoates (10(-4) to 10(-6) M) and 4-aminobenzamidines (10(-3) and 10(-4) M) decreased oocyte penetration when present throughout the assay system. More detailed studies with 8-quinolyl 4-guanidinobenzoate showed that this inhibitor also caused a large decrease in the penetration rate even when only present during the preincubation period of the spermatozoa to induce capacitation. Much smaller decreases were observed when this inhibitor was only present during sperm/egg incubation. By contrast, 4-aminobenzamidine caused a large decrease in the penetration rate when present during sperm/egg incubation but a much smaller one when present during the sperm's preincubation period. The primary action of the inhibitors was not due to a visible effect on sperm motility or forward progression, or to an effect on the oocyte, although treatment of oocytes with inhibitor caused a small decrease in penetration. Inhibition of sperm binding to the oolemma occurred also at times, but this was not directly correlated to the decrease in oocyte penetration. The results are consistent with the fact that a serine proteinase, presumably acrosin, is important for the capacitation, acrosome reaction, and/or oocyte penetration of human spermatozoa. The synthesized aryl 4-guanidinobenzoates are of interest as contraceptive agents because they possess phenols approved by the Food and Drug Administration (United States) for human use and should be relatively nontoxic.
D000818:Animals; D001550:Benzamidines / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D006224:Cricetinae; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008297:Male; D009865:Oocytes / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013084:Sperm-Ovum Interactions / Q000187:drug effects*; D013094:Spermatozoa / Q000502:physiology*
D001550:Benzamidines; D001565:Benzoates; D006146:Guanidines; D011480:Protease Inhibitors; C006500:4-aminobenzamidine