Recently, the endocannabinoid (EC) system and the presence of CB1 receptor (CB1‐R), have been identified in human sperm. However, the effects of EC receptor ligands such as anandamide (N‐arachidonoylethanolamine) and the role of EC system in male fertility is still largely unexplored. In the present study, we investigated the ultrastructural compartmentalization of CB1‐R and analyzed the effects of its stimulation by using a stable analog of anandamide, 2‐methylarachidonyl‐2′‐fluoro‐ethylamide (MET‐F‐AEA). We focused particularly on sperm survival and acrosin activity. The study of human sperm anatomy by transmission electron microscopy with immunogold analysis revealed the location of the CB1‐R prevalently in the sperm membranes of the head and interestingly on the mitochondria. The effect of different concentrations of MET‐F‐AEA from 100 nM to 1 μM evidenced a significant decrease of sperm survival. Interestingly, we analyzed this negative effect at molecular level, testing the EC action on different known sperm survival targets. MET‐F‐AEA‐treatment decreased both pBCL2 and pAkt, two prosurvival proteins, and increased pPTEN expression which is the main regulator of the PI3K/Akt pathway. Moreover, a biphasic effect was observed with increasing MET‐F‐AEA concentrations on the acrosin activity. The blockage of the CB1‐R by using its selective antagonist SR141716 (rimonabant) induced an opposite action on sperm survival supporting a role for this receptor in the biology of the male gamete. Anat Rec, 2010.
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Aquila et al. (2009) studied this question.
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