title: N-Acylethanolamines in human reproductive fluids.
abstract: N-Acylethanolamines (NAEs) are an important family of lipid-signaling molecules. Arachidonylethanolamide (anandamide) (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA) are co-produced from similar phospholipid precursors when neurons are stimulated. AEA is an endogenous agonist (endocannabinoid) for cannabinoid receptors. It binds with higher affinity to type CB1 than to type CB2 cannabinoid receptors. PEA does not bind to CB1, while the hypothesis that it reacts with putative CB2-like receptors has been questioned. OEA does not activate currently known cannabinoid receptors, but it mimics the effects of AEA and cannabinoids in reducing the fertilizing capacity of sea urchin sperm. OEA and PEA also act as entourage compounds by inhibiting the hydrolysis of AEA by fatty acid amide hydrolase. Cannabinoid receptors and/or AEA are present in mammalian reproductive organs including the testis, epididymis, prostate, ovary, uterus, sperm, preimplantation embryo and placenta, as well as prostatic and mammary carcinomas. We now report that analysis by high-performance liquid chromatography/mass spectrometry (HPLC/MS) shows the presence of AEA, PEA, and OEA in human seminal plasma, mid-cycle oviductal fluid, follicular fluid, amniotic fluid, milk, and fluids from malignant ovarian cysts. Previous studies showed that AEA-signaling via cannabinoid receptors regulates capacitation and fertilizing potential of human sperm, early embryonic development and blastocyst implantation into the uterine mucosa of rodents, as well as proliferation of human mammary and prostatic carcinomas. Current results imply that NAEs also may modulate follicular maturation and ovulation, normal and pathological ovarian function, placental and fetal physiology, lactation, infant physiology, and behavior. Collectively, these findings suggest that NAEs in human reproductive fluids may help regulate multiple physiological and pathological processes in the reproductive system, and imply that exogenous cannabinoids delivered by marijuana smoke might impact these processes. This study has potential medical and public policy ramifications because of the incidence of marijuana abuse by adolescents and adults in our society, previously documented reproductive effects of marijuana, and the ongoing debate about medicinal use of marijuana and cannabinoids.
authors.affiliation: Department of Pathology and Anatomical Sciences, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA. schuel@acsu.buffalo.edu
authors.forename: Herbert
authors.initials: H
authors.lastname: Schuel
authors.forename: Lani J
authors.initials: LJ
authors.lastname: Burkman
authors.forename: Jack
authors.initials: J
authors.lastname: Lippes
authors.forename: Kent
authors.initials: K
authors.lastname: Crickard
authors.forename: Ellyn
authors.initials: E
authors.lastname: Forester
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Giuffrida
mesh_terms: D000653:Amniotic Fluid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D063385:Cannabinoid Receptor Modulators; D004983:Ethanolamines / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D005187:Fallopian Tubes / Q000737:chemistry; D005260:Female; D015571:Follicular Fluid / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D008895:Milk, Human / Q000737:chemistry; D006080:Ovarian Follicle / Q000378:metabolism / Q000473:pathology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism; D012661:Semen / Q000737:chemistry / Q000378:metabolism*
chemical_list: D063385:Cannabinoid Receptor Modulators; D004983:Ethanolamines; C022203:N-acylethanolamines; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug