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Title: The Role of the Endocannabinoid System in the Regulation of Human Sperm Function and Male Fertility
Authors: Amoako, Akwasi Atakora
Supervisors: Konje, Justin
Marczylo, Timothy
Willets, Jonathon
Award date: 1-Jan-2013
Presented at: University of Leicester
Abstract: Anandamide (AEA) signalling through the cannabinoid receptors regulates human sperm functions and male reproduction. This signalling pathway is the main mechanism through which Δ9-tetrahydrocannabinol, the active principle of marijuana exerts its adverse effects on male fertility. How deregulation of this endogenous signalling pathway affects human sperm functions remains largely unexplored. The purpose of this study was to elucidate the pathophysiological role of the endocannabinoid system in male fertility. Seminal plasma levels of Anandamide (AEA), Palmitoylethanolamide (PEA) and Oleoylethanolamide (OEA) were quantified by UHPLC-tandem mass spectrometry from 90 semen samples provided by men with normal and abnormal semen parameters. Using qRT-PCR, CB1, CB2, GPR55, NAPEPLD and FAAH mRNA expression profiles were characterized in human spermatozoa from men with normal and abnormal semen parameters. The effects of in-vitro exposure of human spermatozoa to Methanandamide (Meth-AEA), PEA, OEA and Lysophosphatidylinositol (LPI), a potent GPR55 agonist, were evaluated with respect to sperm motility, viability and mitochondrial membrane potential Seminal plasma concentrations (nM) of AEA, PEA and OEA were significantly decreased (P< 0.05) in men with asthenozoospermia (AEA = 0.080 ± 0.01, PEA = 5.45 ± 0.87, OEA = 0.70 ± 0.89), oligoasthenoteratozoospermia (AEA = 0.083 ± 0.01, PEA = 5.27 ± 0.95, OEA = 0.61 ± 0.07) and azoospermia (AEA = 0.056 ± 0.01, OEA = 0.30 ± 0.03) compared to the normozoospermic controls (AEA = 0.198 ± 0.03, PEA = 15.32 ± 2.47, OEA = 1.75 ± 0.25) respectively. CB1 and GPR55 mRNA were significantly decreased (p<0.05) in asthenozoospermia, OAT and teratozoospermic samples compared to the normozoospermic controls. On the other hand, there was no significant difference in the expression of CB2, NAPEPLD and FAAH mRNA between the groups. Meth-AEA significantly decreased sperm motility and viability through inhibition of mitochondrial membrane potential in a dose-dependent manner which was blocked by the CB1 receptor antagonist AM 251. In contrast, PEA, LPI and OEA resulted in significant increases in sperm motility and maintained viability most likely through the GPR55 receptor. The results of this study show that regulation of a normal endocannabinoid-tone may be necessary for the preservation of normal sperm function and male fertility. These observations have potential implications for the role of the exocannabinoid (marijuana) in male fertility.
Type: Thesis
Level: Doctoral
Qualification: PhD
Rights: Copyright © the author. All rights reserved.
Description: Checking document version on request of author 2015-01-28
Appears in Collections:Theses, Dept. of Cancer Studies & Molecular Medicine
Leicester Theses

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