Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormo
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RESEARCH
Open Access
Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones Anthony H Taylor*, Mark Finney, Patricia MW Lam and Justin C Konje
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 (pregnancyassociated 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 AEAmodifying 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. Keywords: Anandamide, cannabinoid receptor, endocannabinoid, miscarriage, PAPP-A, progesterone, β-hCG
Background Successful implantation and maintenance of pregnancy occurs through a complex interaction between fetal and maternal tissues that involves several factors including the hormones estrogen and progesterone [1,2], human chorionic gonadotrophin [3-6], inhibin [5,7,8], pregnancy associated plasma protein (PAPP)-A [6,8,9], and a balance between type 1 T-helper (Th1) * Correspondence: [email protected] Endocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK
and type 2 T-helper (Th2) cytokines [10]. Although a unique immunological interplay is essential for the lack of rejection of the fetus by the mother, little is known about the precise fa
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