Alberto Revelli,
Dario Ghigo,
Federica Moffa,
Marco Massobrio and
Ilan Tur-Kaspa
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 cyclasefamily is responsible for the long-distance interaction betweengametes, as its activation allows sperm chemotaxis toward egg-derivedsubstances, gamete encounter, and fertilization. In specieswith internal fertilization, guanylate cyclase-activating substances,which are secreted by several tissues in the genital tractsof both sexes, deeply affect sperm motility, capacitation, andacrosomal reactivity, stimulating sperm metabolism and promotingthe ability of the sperm to approach the oocyte, interact withit, and finally fertilize it. A complex system of intracellularpathways is activated by guanylate cyclase agonists in spermatozoa.Sperm motility appears to be affected mainly through an increasein intracellular cAMP, whereas the acrosome reaction dependsmore directly on cyclic GMP synthesis. Both cyclic nucleotidesactivate specific kinases and ion signals. A complex cross-talkbetween cAMP- and cyclic GMP-generating systems occurs, resultingin an upward shift in sperm function. Excessive amounts of certainguanylate cyclase activators might exert opposite, antireproductiveeffects, increasing the oxidative stress on sperm membranes.In view of the marked influence exerted by guanylate cyclase-activatingsubstances on sperm function, it seems likely that guanylatecyclase activation or inhibition may represent a new approachfor the diagnosis and treatment of male and/or female infertility.
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