title: Anandamide modulates human sperm motility: implications for men with asthenozoospermia and oligoasthenoteratozoospermia.
abstract: OBJECTIVE
  What are the levels of anandamide (N-arachidonoylethanolamide, AEA) in human seminal plasma and how are these related to abnormal spermatozoa?
  
  
  CONCLUSIONS
  Seminal plasma AEA levels were lower in men with asthenozoospermia and oligoasthenoteratozoospermia compared with normozoospermic men.
  
  
  BACKGROUND
  AEA, a bioactive lipid, synthesized from membrane phospholipids may signal through cannabinoid receptors (CB1 and CB2) to regulate human sperm functions and male reproduction by modulating sperm motility, capacitation and the acrosome reaction in vitro. Local AEA levels are regulated by the synthetic and degradative enzymes, NAPE-PLD and FAAH, respectively. How the deregulation of this endogenous signalling pathway affects human sperm function(s) is not clear.
  
  
  METHODS
  This was a cross-sectional study of 86 men presenting at an infertility clinic for semen analysis over a period of 2 years.
  
  
  METHODS
  AEA was quantified, by ultra-high performance liquid chromatography-tandem mass spectrometry, in seminal plasma from 86 volunteers. Using qRT-PCR, CB1, CB2, NAPE-PLD and FAAH transcript levels were determined in spermatozoa from men with normozoospermia, asthenozoospermia, oligoasthenoteratozoospermia and teratozoospermia. Normal spermatozoa were exposed in vitro to methanadamide (meth-AEA) to determine its effect on sperm motility, viability and mitochondrial activity.
  
  
  RESULTS
  Seminal plasma AEA levels (mean ± SEM) were significantly lower in men with asthenozoospermia (0.080 ± 0.01 nM; P < 0.05) or oligoasthenoteratozoospermia (0.083 ± 0.01 nM; P < 0.05) compared with normozoospermic men (0.198 ± 0.03 nM). In addition, the levels of spermatozoal CB1 mRNA were significantly decreased in men with asthenozoospermia (P < 0.001) or oligoasthenoteratozoospermia (P < 0.001) compared with normozoospermic controls. Supra-physiological levels of meth-AEA decreased sperm motility and viability, probably through CB1-mediated inhibition of mitochondrial activity.
  
  
  CONCLUSIONS
  The inhibitory effect of meth-AEA was only shown in vitro and may not reflect what happens in vivo.
  
  
  CONCLUSIONS
  As the regulation of the endocannabinoid system appears to be necessary for the preservation of normal sperm function and male fertility, there may be implications for the adverse reproductive consequences of marijuana use. Exocannabinoids, such as Δ(9)-THC, are likely to compete with endocannabinoids at the cannabinoid receptors, upsetting the finely balanced endocannabinoid signalling system. The importance of the endocannabinoid system makes it an attractive target for pharmacological interventions to control male fertility.
  
  
  BACKGROUND
  This work was funded in part by miscellaneous educational funds from the University Hospitals of Leicester National Health Services Trust to support the Endocannabinoid Research Laboratory of University of Leicester. The authors declare no competing interests.
authors.affiliation: Endocannabinoid Research Group, Reproductive Science Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester LE2 7LX, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Amoako
authors.forename: T H
authors.initials: TH
authors.lastname: Marczylo
authors.forename: E L
authors.initials: EL
authors.lastname: Marczylo
authors.forename: J
authors.initials: J
authors.lastname: Elson
authors.forename: J M
authors.initials: JM
authors.lastname: Willets
authors.forename: A H
authors.initials: AH
authors.lastname: Taylor
authors.forename: J C
authors.initials: JC
authors.lastname: Konje
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D063388:Endocannabinoids / Q000378:metabolism / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007248:Infertility, Male / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism; D012661:Semen / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D053719:Tandem Mass Spectrometry; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063388:Endocannabinoids; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000099252:Fatty Acid Amide Hydrolases; C581518:NAPEPLD protein, human; C078814:anandamide
keywords: anandamide; endocannabinoid system; male infertility; seminal plasma; spermatozoa