Characterization of the Endocannabinoid System in Early Human Pregnancy

Abstract

In recent years, it has been demonstrated that high circulating levels of the endogenous cannabinoid anandamide, resulting from low expression of its metabolizing enzyme fatty acid amide hydrolase (FAAH), may contribute to spontaneous miscarriage and poor outcome in women undergoing in vitro fertilization. The site of action of this compound, however, has not been determined. In this study, we examined the distribution of the cannabinoid receptors, CB1 and CB2, and the endocannabinoid-metabolizing enzyme FAAH in first trimester human placenta. Here, we show that FAAH is expressed throughout the human first trimester placenta, in extravillous trophoblast columns, villous cytotrophoblasts, syncytiotrophoblasts, and macrophages. Furthermore, FAAH mRNA levels appear to be regulated during gestation, with levels peaking at 11 wk before declining again. The immune system-associated cannabinoid CB2 receptors were localized only to placental macrophages. Interestingly, the cannabinoid receptor CB1 was not identified in first trimester placenta despite having previously been shown to be present in placental tissues at term. These findings suggest that the placenta may form a barrier preventing maternal-fetal transfer of anandamide and/or modulate local levels of anandamide by regulation of FAAH expression with gestation.

The role of endocannabinoids in pregnancy

“…It has been shown that the expression of placental CB1 receptor protein is elevated 2.5-fold in spontaneous miscarriage in the first trimester compared with levels observed in voluntary termination ). In addition, Trabucco et al found that the immunostaining of the CB1 receptor is poorly detected in placental villi from elective surgical terminations, which supports earlier observations from our laboratory that the expression of CB1 receptor mRNA and protein is not readily detected in the first-trimester placentae (weeks 9-13 of gestation; Helliwell et al 2004). However, for gestational age-matched placentae of weeks 7-8, the expression of CB1 receptor protein in the trophoblast, mesenchymal core and decidua was approximately twofold lower in spontaneous miscarriage than in elective surgical termination (Taylor et al 2011).…”

Induction of Krox-24 by Endogenous Cannabinoid Type 1 Receptors in Neuro2A Cells Is Mediated by the MEK-ERK MAPK Pathway and Is Suppressed by the Phosphatidylinositol 3-Kinase Pathway

“…PCR primers were as follows: CB1 forward, 5Ј-atgaagtcgatcctagatggccttgcaga-3Ј, and CB1 reverse, 5Ј-tcacagagcctcggcagacgtg-3Ј (27). CB1 primers amplify the 1.5-kb coding region of the CB1 receptor.…”

Effect of social isolation on CB1 and D2 receptor and fatty acid amide hydrolase expression in rats

“…The antibody was affinity purified and recognized recombinant FAAH expressed in HEK293 cells, but exhibited no detectable immunoreactivity to wild-type cells and recognized a single band by Western immunoblot (data not shown). Additionally, Helliwell et al (2004) have demonstrated the utility of this antibody for immunocytochemistry (Harkany et al, 2003;Helliwell et al, 2004). All three antibodies were generated in the laboratory of authors CK and KM at the University of Washington.…”