Stimulation of the nitric oxide/cyclic guanosine monophosphate signaling pathway elicits human sperm chemotaxis in vitro

ObjectiveTo investigate whether nitric oxide (NO) may attract human spermatozoa via activation of the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway.DesignProspective study.SettingAcademic research institution.Patient(s)Seven normozoospermic patients belonging to couples presenting for infertility evaluation.Intervention(s)Sperm samples were processed by the swim-up technique.Main Outcome Measure(s)Sperm chemotaxis detected by a choice device (specially designed three-well plexiglass chamber), intracellular level of cGMP (by radioimmunoassay), and sperm motility parameters (by computer-assisted sperm analysis).Result(s)After a 20-minute incubation, the NO donor S-nitrosoglutathione (GSNO) increased the synthesis of cGMP and exerted a significant chemoattraction on human spermatozoa. The GSNO-induced migration of sperm was inhibited by PTIO (a NO scavenger), ODQ (an sGC inhibitor), and Rp-8-Br-cGMPS (an inhibitor of cGMP-dependent protein kinases). The cell-permeating cGMP analog 8-Br-cGMP acted as a potent chemoattractant per se: this effect was inhibited by Rp-8-Br-cGMPS.Conclusion(s)These data suggest that NO may exert a chemoattractant effect on human spermatozoa and that the signal transduction involves the activation of sGC, the synthesis of cGMP, and the activation of cGMP-dependent protein kinases.