Effects of nitric oxide on human spermatozoa: evidence that nitric oxide decreases sperm motility and induces sperm toxicity.
Endogenous nitric oxide (NO) is an important functional mediator in several physiological systems, including the reproductive system. However, when generated in excessive amounts for long periods, mainly during immunological reactions, NO is cytotoxic and cytostatic for invading microbes, as well as for the cells generating it and the tissues present around it. Since infertility associated with urogenital tract infection in males and females is also accompanied by reduced sperm motility and viability, it is possible that reduced fertility in these patients is due to NO-induced sperm toxicity. We therefore evaluated the direct effects of NO, chemically derived from S-nitroso-N-acetylpenicillamine (SNAP, 0.012-0.6 mM) and sodium nitroprusside (SNP, 0.25-2.5 mM), on the motility and viability of human spermatozoa. Furthermore, we tested whether inhibition of NO synthesis prevents sperm motility and viability by incubating washed total cells present in the semen (spermatozoa, round cells) with N-nitro-L-arginine-methyl-ester (L-NAME), a NO synthesis inhibitor. Treatment of purified spermatozoa with SNAP or SNP decreased forward progressive sperm motility and straight line velocity, and also increased the percentage of immotile spermatozoa in a concentration-dependent manner. Furthermore, the percentage of immotile spermatozoa positively correlated with the percentage of dead spermatozoa. In contrast to freshly prepared SNAP, SNAP preincubated for 48 h had no effect on the motility and viability of the spermatozoa. Furthermore, as compared to untreated controls, a significantly higher percentage of forward progressive sperm motility as well as viability (P < 0.05) was maintained in washed semen incubated with L-NAME (0.15 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
Rosselli
M
M
Department of Obstetrics and Gynaecology, University Hospital, Zurich, Switzerland.
Dubey
R K
RK
Imthurn
B
B
Macas
E
E
Keller
P J
PJ
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D012661:Semen / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000502:physiology
D009566:Nitrates; D009573:Nitrites; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester