title: Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones.
abstract: BACKGROUND
  In early pregnancy, increased plasma levels of the endocannabinoid anandamide (AEA) are associated with miscarriage through mechanisms that might affect the developing placenta or maternal decidua.
  
  
  METHODS
  In this study, we compare AEA levels in failed and viable pregnancies with the levels of the trophoblastic hormones (beta-human chorionic gonadotrophin (beta-hCG), progesterone (P4) and (pregnancy-associated placental protein-A (PAPP-A)) essential for early pregnancy success and relate that to the expression of the cannabinoid receptors and enzymes that modulate AEA levels.
  
  
  RESULTS
  The median plasma AEA level in non-viable pregnancies (1.48 nM; n = 20) was higher than in viable pregnancies (1.21 nM; n = 25; P = 0.013), as were progesterone and beta-hCG levels (41.0 vs 51.5 ng/mL; P = 0.052 for P4 and 28,650 vs 6,560 mIU/L; P = 0.144 for beta-hCG, respectively, but were not statistically significant). Serum PAPP-A levels in the viable group were approximately 6.8 times lower than those in the non-viable group (1.82 vs 12.25 mg/L; P = 0.071), but again these differences were statistically insignificant. In the spontaneous miscarriage group, significant correlations between P4 and beta-hCG, P4 and PAPP-A and AEA and PAPP-A levels were observed. Simultaneously, immunohistochemical distributions of the two main cannabinoid receptors and the AEA-modifying enzymes, fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), changed within both the decidua and trophoblast.
  
  
  CONCLUSIONS
  The association of higher AEA levels with early pregnancy failure and with beta-hCG and PAPP-A, but not with progesterone concentrations suggest that plasma AEA levels and pregnancy failure are linked via a mechanism that may involve trophoblastic beta-hCG, and PAPP-A, but not, progesterone production. Although the trophoblast, decidua and embryo contain receptors for AEA, the main AEA target in early pregnancy failure remains unknown.
authors: Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK. aht3@le.ac.uk
authors: Anthony H
authors: AH
authors: Taylor
authors: Mark
authors: M
authors: Finney
authors: Patricia Mw
authors: PM
authors: Lam
authors: Justin C
authors: JC
authors: Konje
mesh_terms: D000028:Abortion, Induced; D000022:Abortion, Spontaneous / Q000097:blood / Q000378:metabolism; D000328:Adult; D000581:Amidohydrolases / Q000378:metabolism; D001095:Arachidonic Acids / Q000097:blood*; D063385:Cannabinoid Receptor Modulators / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D003656:Decidua / Q000378:metabolism; D063388:Endocannabinoids; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D010739:Phospholipase D / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000097:blood*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D043882:Receptors, Cannabinoid / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D018997:Chorionic Gonadotropin, beta Subunit, Human; D063388:Endocannabinoids; D006728:Hormones; D010739:Phospholipase D; D053284:Polyunsaturated Alkamides; D011266:Pregnancy-Associated Plasma Protein-A; D011374:Progesterone; D043882:Receptors, Cannabinoid; D000099252:Fatty Acid Amide Hydrolases; C078814:anandamide