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 se veral physiological systems, including the reproductive system, Howeve r when generated in excessive amounts for long periods, mainly during immunological reactions. NO is cytotoxic and cytostatic for invading m icrobes, as well as for the cells generating it and the tissues presen t around it, Since infertility associated with urogenital tract infect ion in males and females is also accompanied by reduced sperm motility and viability, it is possible that reduced fertility in these patient s is due to NO-induced sperm toxicity. We therefore evaluated the dire ct effects of NO, chemically derived from S-nitroso-N-acetylpenicillam ine (SNAP 0.012-0.6 mM) and sodium nitroprusside (SNP, 0.25-2.5 mM), o n the motility and viability of human spermatozoa. Furthermore, we tes ted whether inhibition of NO synthesis prevents sperm motility and via bility by incubating washed total cells present in the semen (spermato zoa, round cells) with N-nitro-L-arginine-methyl-ester (L-NAME), a NO synthesis inhibitor. Treatment of purified spermatozoa with SNAP or SN P decreased forward progressive sperm motility and straight line veloc ity, and also increased the percentage of immotile spermatozoa in a co ncentration-dependent manner. Furthermore, the percentage of immotile spermatozoa positively correlated with the percentage of dead spermato zoa, In contrast to freshly prepared SNAP, SNAP preincubated for 48 h had no effect on the motility and viability of the spermatozoa, Furthe rmore, as compared to untreated controls, a significantly higher perce ntage of forward progressive sperm motility as well as viability (P < 0.05) was maintained in washed semen incubated with L-NAME (0.15 mM). Seminal plasma concentrations of nitrite-nitrate (stabile metabolites of N0)/10(6) spermatozoa correlated positively (P < 0.05) with the per centage of immotile spermatozoa, Our results suggest that NO can cause sperm toxicity as wed as inhibit sperm motility. In conclusion, exces sive NO synthesis in response to infection and inflammation could be a n important factor contributing to functional change of the spermatozo a, leading to their dysfunction and to infertility.