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.


METHODS
Prospective study.


METHODS
Academic research institution.


METHODS
Seven normozoospermic patients belonging to couples presenting for infertility evaluation.


METHODS
Sperm samples were processed by the swim-up technique.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Miraglia
Erica
E
Department of Genetics, Biology and Biochemistry, University of Torino, 10126 Torino, Italy.
Rullo
Maria Luisa
ML
Bosia
Amalia
A
Massobrio
Marco
M
Revelli
Alberto
A
Ghigo
Dario
D
D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000819:agonists / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology*
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006152:Cyclic GMP