DOES ENDOTHELIN-1 AFFECT HUMAN SPERMATOZOA FUNCTION

PROBLEM: It has been reported that massive amounts of immunoreactive e ndothelins (ET(s)) exist in human seminal plasma. However, the physiol ogical role of ET(s) in seminal plasma remains to be determined. We sp eculated that ET(s) might affect sperm function. METHOD: The present s tudy was designed to investigate the effect of endothelium-l (ET-1) on : (a) sperm motion parameters, (b) hyperactivated motility, (c) sperm- zona pellucida-binding capacity, (d) sperm-oocyte penetration capacity , (e) acrosome reaction and its prerequisite, an increase in intracell ular Ca2+ concentration ([Ca2+](i)), and to examine (f) the presence o f binding sites for ET-1 in human sperm. Forty-six semen ejaculates fr om 14 fertile men were assessed under capacitating conditions after se paration of the motile sperm The Jones Institute for fraction by wash and swim-up. RESULTS: ET-1 (1 mu m) exhibited significant stimulatory effects on sperm velocity at 30 min (P = 0.01), amplitude of lateral h ead displacement (ALH)(max) (P = 0.05), and ALH(mean) at 60 min (P = 0 .04) in some samples (n = 10). However, these effects were not observe d in experiments using a larger number of samples (n = 39). ET-1 had n o effect on hyperactivated motility of sperm at 30 min to 24 h. Neithe r ET-3 nor IRL 1620, a selective ET(3) receptor agonist, affected sper m motion parameters or hyperactivated motility. ET-1 did not affect sp erm-zona-binding capacity, sperm-oocyte penetration capacity, acrosome reaction, or [Ca2+](i) of sperm. Specific binding sites for ET-1 were not detected on the cell surface of human sperm. CONCLUSIONS: Althoug h ET-1 is present in massive amounts in human seminal plasma and may h ave the capacity to alter the quality of motile sperm in some samples, a physiological role of ET-1 in the modulation of the function of mat ure, ejaculated sperm still remains unknown.