Abstract 543: Local Uterine Ang-(1-7) Infusion Augments Expression of Cannabinoid Receptors and Differentially Alters Endocannabinoid Metabolizing Enzymes in the Decidualized Uterus of Pseudopregnant Rats

Abstract

Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamine (AEA), the endogenous ligand for the CB 1 and CB 2 receptor (R), interfere with receptivity of the blastocyst. Ang-(1-7) is present in the decidualized zones of the implantation site (IS) at early pregnancy and is down-regulated in the IS in normal pregnancy. We determined the effects of intra-uterine Ang-(1-7) on the EC system in the decidualized uterus. Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment. Decidualization was induced by infusion of phosphate buffered saline into the left horn (infused); the right horn was non-infused. Ang-(1-7) (24 μg/kg/hr) or vehicle was given into one of the two uterine horns. CB 1 R mRNA was reduced by decidualization but increased in the presence of Ang-(1-7) . CB 2 R mRNA was increased by decidualization and by Ang-(1-7) ( Figure). The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (1.0 ± 0.07 vs. 0.13 ± 0.03 U, p<0.01) and remained reduced by Ang-(1-7), whereas the enzyme metabolizing 2-arachidonylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (1.06 ± 0.11 vs. 1.34 ± 0.13 U, ns) and increased by Ang-(1-7) (1.32 ± 0.19 vs. 2.27 ± 0.23 U, p<0.01). These findings report for the first time that Ang-(1-7) augments the expression of CB 1 R, CB 2 R and MAGL in the decidualized uterus. The effects of Ang-(1-7) to disrupt regulation of the EC system may interfere with the early events of decidualization, including alterations in angiogenesis, apoptosis, permeability, and receptivity.