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

OBJECTIVE: To investigate whether nitric oxide (NO) may attract human spermatozoa via activation of the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway. DESIGN: Prospective study. SETTING: Academic 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.