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Guanylate Cyclase Activity and Sperm Function

Department of Obstetrical and Gynecological Sciences (A.R., F.M., M.M.), University of Torino, S. Anna Hospital, Torino, Italy 10126; Department of Genetics, Biology and Biochemistry (D.G.), University of Torino, 10126 Torino, Italy; and In Vitro Fertilization Unit (I.T.-K.), Department of Obstetrics and Gynecology, Barzilai Medical Center, Ben-Gurion University, Askelon, Israel 78306

Correspondence: Address all correspondence and requests for reprints to: Alberto Revelli, M.D., Department of Obstetrical and Gynecological Sciences, University of Torino, S. Anna Hospital, Via Baiardi 43, 10126 Torino, Italy. E-mail: fertisave{at}yahoo.com

In species with external fertilization, the guanylate cyclase family is responsible for the long-distance interaction between gametes, as its activation allows sperm chemotaxis toward egg-derived substances, gamete encounter, and fertilization. In species with internal fertilization, guanylate cyclase-activating substances, which are secreted by several tissues in the genital tracts of both sexes, deeply affect sperm motility, capacitation, and acrosomal reactivity, stimulating sperm metabolism and promoting the ability of the sperm to approach the oocyte, interact with it, and finally fertilize it. A complex system of intracellular pathways is activated by guanylate cyclase agonists in spermatozoa. Sperm motility appears to be affected mainly through an increase in intracellular cAMP, whereas the acrosome reaction depends more directly on cyclic GMP synthesis. Both cyclic nucleotides activate specific kinases and ion signals. A complex cross-talk between cAMP- and cyclic GMP-generating systems occurs, resulting in an upward shift in sperm function. Excessive amounts of certain guanylate cyclase activators might exert opposite, antireproductive effects, increasing the oxidative stress on sperm membranes. In view of the marked influence exerted by guanylate cyclase-activating substances on sperm function, it seems likely that guanylate cyclase activation or inhibition may represent a new approach for the diagnosis and treatment of male and/or female infertility.

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