title: The effect of mifepristone (RU486) on the endocannabinoid system in human plasma and first-trimester trophoblast of women undergoing termination of pregnancy.
abstract: BACKGROUND
  High anandamide (AEA) concentrations are detrimental for implantation and early pregnancy. Progesterone, essential for pregnancy, may keep AEA levels low by increasing fatty acid amide hydrolase (FAAH) expression. Here the effect of RU486, a P4 antagonist used to initiate medical termination of pregnancy (MTOP), on plasma AEA concentrations and the endocannabinoid system (ECS) in trophoblasts was examined.
  
  
  OBJECTIVE
  Quantification of the endocannabinoid concentrations and expression of the ECS in trophoblast tissue of MTOP women and women undergoing surgical termination of pregnancy (STOP).
  
  
  METHODS
  A prospective study at the University Hospitals of Leicester National Health Service Trust.
  
  
  METHODS
  AEA, N-oleoylethanolamine (OEA), and N-palmitolylethanolamine (PEA) concentrations in trophoblast tissues and blood samples from 68 MTOP and 15 STOP were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry. ECS expression was determined by immunohistochemistry, quantitative RT-PCR, and Western blotting.
  
  
  RESULTS
  Concentrations of AEA, OEA, and PEA were significantly higher in MTOP than STOP trophoblasts (P = .0062, P = .016, and P = .0029, respectively), whereas no significant differences in plasma AEA, OEA, and PEA concentrations were observed even though plasma AEA and PEA concentrations were significantly (P = .005 and P = .025, respectively) increased the day after RU486 administration in women undergoing MTOP. Changes in the immunohistochemical densities of the AEA modifying enzymes N-acylphophatidylethanolamine-phospholipase D (NAPE-PLD) and FAAH, and the cannabinoid receptors (CB1 and CB2) were observed with increased NAPE-PLD, FAAH, and CB1 expression seen in the trophoblast of MTOP patients.
  
  
  CONCLUSIONS
  Trophoblast after MTOP demonstrated high AEA concentrations with increased expression of NAPE-PLD, FAAH, and CB1.
authors.affiliation: Endocannabinoid Research Group (T.K., T.H.M., A.H.T., J.C.K.), Reproductive Sciences, Leicester Royal Infirmary, Leicester, Leicestershire, LE2 7LX, United Kingdom; Systems Toxicology (E.L.M.), Medical Research Council Toxicology Unit, Hodgkin Building, Lancaster Road, Leicester, LE1 9HN, United Kingdom; and Contraception, Sexual, and Reproductive Health Services (E.O.), University Hospitals of Leicester National Health Service (NHS) Trust, St Peters Health Centre, Leicester, LE2 0TA, United Kingdom.
authors.forename: Tülay
authors.initials: T
authors.lastname: Karasu
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Marczylo
authors.forename: Emma L
authors.initials: EL
authors.lastname: Marczylo
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Taylor
authors.forename: Emeka
authors.initials: E
authors.lastname: Oloto
authors.forename: Justin C
authors.initials: JC
authors.lastname: Konje
mesh_terms: D000028:Abortion, Induced / Q000379:methods; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D063388:Endocannabinoids / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D015735:Mifepristone / Q000008:administration & dosage*; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects* / Q000378:metabolism; D055815:Young Adult
chemical_list: D063388:Endocannabinoids; D015735:Mifepristone