A new role of anandamide in human sperm: focus on metabolism

The endocannabinoid system and the presence of CB1 receptor (CB1-R) target of the anandamide were identified in human sperm, however the anandamide action in this context needs to be further elucidated. At this purpose we analyzed the effects of anandamide on human sperm capacitation and motility. Afterwards, we focused on lipid and glucose sperm metabolism and also investigated the interrelationship between anandamide and insulin secretion by sperm. By intracellular free Ca2+ content assay and proteins tyrosine phosphorylation, we evidenced that anandamide did not induce capacitation process and a negative effect was obtained on sperm motility. The blockage of CB1-R by the specific antagonist SR141716 increased both capacitation and sperm motility suggesting an involvement of the CB1-R in the acquisition of sperm fertilizing activity. The evaluation of the triglycerides content, lipase and acyl-CoA dehydrogenase activities, suggest that anandamide exerts a lipogenetic effect on human sperm lipid metabolism. Concerning the glucose metabolism, anandamide increases GSK3 phosphorylation indicating that it is involved in the accumulation of energy substrates. G6PDH activity was not affected by anandamide. Interestingly, AEA is involved in insulin secretion by sperm. As insulin had been demonstrated to be an autocrine factor that triggers capacitation, the endocannabinoid might be inserted in the signaling cascade that induces this process. Altogether these findings highlight a pivotal involvement of the CB1-R in the control of sperm energy homeostasis and propose a new site of action for endocannabinoids in the control of energy metabolism.