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Human Sperm Express Cannabinoid Receptor Cb₁, the Activation of Which Inhibits Motility, Acrosome Reaction, and Mitochondrial Function

Department of Medical and Surgical Sciences, Clinica Medica 3 (M.R.); Department of Biological Chemistry (F.I.P., G.C.); and Department of Histology, Microbiology, and Medical Biotechnologies, Center of Male Gamete Cryopreservation (M.F., C.F.), University of Padova, Padova, Italy

Address all correspondence and requests for reprints to: Dr. M. Rossato, Department of Medical and Surgical Sciences, Clinica Medica 3, University of Padova, Via Ospedale 105, 35128 Padova, Italy. E-mail: marco.rossato{at}unipd.it.

Cannabinoids and endocannabinoids negatively influence sperm functions. These substances have been demonstrated in many mammalian tissues, including male and female reproductive tracts, and previous studies have shown the presence of functional receptors for cannabinoids in human sperm. The present study, by means of RT-PCR and Western blot techniques, demonstrates that human sperm express the CB₁, but not CB₂, cannabinoid receptor (CB-R) subtype located in the head and middle piece of the sperm. The activation of this receptor by anandamide reduces sperm motility and inhibits capacitation-induced acrosome reaction. Activation of the CB₁-R did not induce any variation in sperm intracellular calcium concentrations, but produced a rapid plasma membrane hyperpolarization that was reduced by the K⁺ channel blocker tetraethylammonium. The effects of anandamide on human sperm motility were dependent on the reduction of sperm mitochondrial activity as determined by rhodamine 123 fluorescence. The specificity of anandamide effects in human sperm were confirmed by the effects of the CB₁-R antagonist SR141716. These findings provide additional evidence that human sperm express functional CB₁-R, the activation of which negatively influences important sperm functions, and suggest a possible role for the cannabinoid system in the pathogenesis of some forms of male infertility.

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