title: 2-arachidonoylglycerol levels are increased in leukocytospermia and correlate with seminal macrophages.
abstract: Evidence has been produced that macrophages can actively generate endocannabinoids (eCBs) in response to inflammatory stimuli. As eCBs are involved in the control of several physiological processes, including reproduction, here, we explored whether seminal levels of the eCBs, N-arachidonoylethanolamine (AEA), and 2-arachidonoylglycerol (2-AG), were higher in the presence of leukocytospermia, and were correlated with semen concentration of macrophages. The content of AEA and 2-AG was measured by high-performance liquid chromatography/mass spectrometry in seminal plasma of ejaculates from 18 leukocytospermic patients (>1 × 106leukocytes/mL) and 21 normozoospermic controls. In the same ejaculates, round cells were phenotyped by flow-cytometry as leukocytes (CD45+), macrophages (CD14+), and activated macrophages (CD14+, HLA-DR+). The levels of 2-AG, but not of AEA, were significantly higher in ejaculates from leukocytospermic patients than in controls and exhibited a significant correlation with semen concentration of macrophages and activated macrophages. Significant associations of 2-AG with macrophages and activated macrophages persisted after adjustment for semen volume and sperm concentration. In conclusion, here we provide evidence that seminal plasma levels of 2-AG are higher in the presence of leukocytospermia, as a marker of macrophages activation. Further studies are warranted to elucidate possible clinical implications.
authors.affiliation: San Raffaele Sulmona Institute, Sulmona, Italy.|Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Barbonetti
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy.|Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Bisogno
authors.affiliation: Faculty of Bioscience and Technology for Food, Agriculture and Environment, University of Teramo, Teramo, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Battista
authors.affiliation: Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Pozzuoli, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piscitelli
authors.affiliation: Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Micillo
authors.affiliation: Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Francavilla
authors.affiliation: Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Andrology Unit, Department of Life, Health and Environment Sciences, University of L'Aquila, L'Aquila, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Francavilla
mesh_terms: D001095:Arachidonic Acids / Q000378:metabolism*; D063388:Endocannabinoids / Q000378:metabolism*; D005434:Flow Cytometry; D005989:Glycerides / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008297:Male; D053284:Polyunsaturated Alkamides; D012661:Semen / Q000166:cytology / Q000378:metabolism*; D055101:Semen Analysis; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C078814:anandamide
keywords: 2-arachidonoylglycerol; anandamide; endocannabinoids; flow-cytometry; leukocytes