Aims: In this review, we shall summarize the current knowledge on the endocannabinoid system (ECS), and on its involvement in the multifaceted process of male reproduction. In particular, we shall discuss the role of ECS in sperm biology and Sertoli cell proliferation and death, showing how endocannabinoids may regulate spermatogenesis and reproductive potential. Data synthesis: The available evidence highlights the existence of a distinctive network, including endocannabinoids and sex hormones, that warrants a successful pregnancy in mammals. in particular, it appears that the endocannabinoid-degrading enzyme FAAH (fatty acid amide hydrolase) has a central role in this array of signals, because it controls several steps of sperm biology, from motility to capacitation and acrosome reaction. Since the regulation of FAAH activity and expression by autocrine and paracrine factors may occur through genomic or non-genomic mechanisms mediated by type-1 cannabinoid receptor (CB1R) signaling, we also raise concerns about the use of CB1R agonists (like marijuana) or antagonists (like the anti-obesity drug Acomplia (R)) in subjects of reproductive age. Conclusion: Based on the present data, we point out that FAAH might be a novel and potentially important target for the development of next generation therapeutics against infertility. In particular, a reduced reproductive potential seems to be paralleled by defective FAAH, suggesting that therapeutics able to enhance, rather than inhibit, enzyme activity might be useful fertility enhancers. (C) 2009 Elsevier Ltd. All rights reserved.
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