Endocannabinoid System in First Trimester Placenta: Low FAAH and High CB1 Expression Characterize Spontaneous Miscarriage

• Published in: Placenta (Eastbourne) 2009-06, Vol.30 (6), p.516-522
• Main Authors: Trabucco, E, Acone, G, Marenna, A, Pierantoni, R, Cacciola, G, Chioccarelli, T, Mackie, K, Fasano, S, Colacurci, N, Meccariello, R, Cobellis, G, Cobellis, L
• Format: Article
• Language: English
• Subjects: Abortion, Induced; Abortion, Spontaneous - genetics; Abortion, Spontaneous - metabolism; Adult; Amidohydrolases - metabolism; Animals; Biological and medical sciences; Cannabinoid Receptor Modulators - genetics; Cannabinoid Receptor Modulators - metabolism; Cannabinoid Receptor Modulators - physiology; Case-Control Studies; CB1; Embryology: invertebrates and vertebrates. Teratology; Endocannabinoid system; Endocannabinoids; FAAH; Female; Fundamental and applied biological sciences. Psychology; Humans; Internal Medicine; Male; Mice; Miscarriage; Obstetrics and Gynecology; Phospholipase D - genetics; Phospholipase D - metabolism; Placenta; Placenta - metabolism; Pregnancy; Pregnancy Trimester, First - genetics; Pregnancy Trimester, First - metabolism; Receptor, Cannabinoid, CB1 - metabolism; Young Adult
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2009.03.015

Abstract Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were the first endocannabinoids to be characterized, that bind two G protein-coupled receptors, CB1 and CB2. AEA synthesized by multiple pathways, including NAPE-specific phospholipase D (NAPE-PLD) and degraded by the fatty acid amide hydrolase (FAAH). AEA levels are critical in regulating embryo development and the “window” of implantation. We examined the expression of nape-pld mRNA, CB1 and FAAH in human placenta hypothesizing that their altered signaling may contribute to spontaneous miscarriage. First trimester placentas from women with spontaneous miscarriage (group 1) were matched with placentas from women who underwent termination (group 2). Nape-pld expression was analyzed by RT-PCR; CB1 and FAAH expression by Western blot and immunohistochemistry. Nape-pld mRNA expression was higher in group 2 than in group 1. Western blot analysis revealed higher CB1 expression and lower or absent FAAH in group 1 than in group 2. Immunohistochemistry confirmed CB1 and FAAH signals in group 1 and group 2 placentas, respectively. Human placenta contains the enzymes to synthesize AEA. Moreover, placental tissue represents a target for endocannabinoids whose activity may regulate pregnancy outcome. In particular, very low or absent FAAH and high CB1 levels correspond with spontaneous miscarriage.