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

Human sperm anatomy: ultrastructural localization of the cannabinoid1 receptor and a potential role of anandamide in sperm survival and acrosome reaction. / Aquila, Saveria; Guido, C; Santoro, A; Perrotta, I; Laezza, C; Bifulco, M; Ando', Sebastiano. - In: THE ANATOMICAL RECORD. - ISSN 1932-8486. - 293:2(2010), pp. 298-309.

Human sperm anatomy: ultrastructural localization of the cannabinoid1 receptor and a potential role of anandamide in sperm survival and acrosome reaction.

AQUILA, Saveria;ANDO', Sebastiano
2010

Abstract

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
male genital tract; human sperm anatomy
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/135101
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