期刊
ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY
卷 293, 期 2, 页码 298-309出版社
WILEY
DOI: 10.1002/ar.21042
关键词
CB1-R; anandamide; sperm; male reproduction; SR141716
资金
- Associazione Educazione e Ricerca Medica Salernitana, ERMES
- PRIN-MIUR
- Ex 60%-2007
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-arachidonoylethanol-amine) 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 mu M 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, 293:298-309, 2010. (C) 2009 Wiley-Liss, Inc.
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