Abstract
BackgroundEndocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1–7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation. We determined the effects of intra-uterine angiotensin-(1–7) [Ang-(1–7)] (24 microg/kg/h) or vehicle given into the left uterine horn on the ECs in the decidualized uterus.MethodsOvariectomized rats were sensitized for the decidual cell reaction by steroid treatment and decidualization was induced by a bolus of oil injected into the left horn; the right horn served as a control.ResultsDecidualization increased endometrial permeability (3.1+/−0.2 vs. 7.1+/−0.5 uterus/muscle of cpm of (125)I-BSA, p < 0.0001). VEGF mRNA was increased by the decidualization (1.4-fold, p < 0.05) and by Ang-(1–7) (2.0-fold, p < 0.001). CB1R mRNA was reduced by decidualization (2.7-fold, p < 0.001), but increased by Ang-(1–7) (1.9-fold, p < 0.05). CB2R mRNA was increased by decidualization (4-fold, p < 0.05) and by Ang-(1–7) (2.4-fold, p < 0.001). The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (7.8 fold, p < 0.001) and unchanged by Ang-(1–7) (p > 0.05), whereas the enzyme metabolizing 2-arachidonoylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (p > 0.05) and increased by Ang-(1–7) (1.7 fold, p < 0.001).ConclusionsThese findings report for the first time that Ang-(1–7) augments the expression of CB1R, CB2R and MAGL in the decidualized uterus and thus may interfere with the early events of decidualization.
Highlights
Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy
The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (7.8 fold, p < 0.001) and unchanged by Ang-(1–7) (p > 0.05), whereas the enzyme metabolizing 2-arachidonoylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (p > 0.05) and increased by Ang-(1–7) (1.7 fold, p < 0.001). These findings report for the first time that Ang-(1–7) augments the expression of CB1R, Endocannabinoid receptors (CB2R) and MAGL in the decidualized uterus and may interfere with the early events of decidualization
Permeability measured as the ratio of radiolabeled I(125)-albumin in the uterus relative to the radioactivity of skeletal muscle albumin increased with decidualization, but this increase was unchanged with Ang-(1–7) treatment
Summary
Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. We discovered that in early normotensive pregnancy the renin-angiotensin system (RAS) [Ang–(1–7) and Ang II] was down-regulated in the uterus as compared to virgin animals and in the implantation site (IS) as compared to associated with the IS as compared to the IIS and are required for the receptivity of the blastocyst’s attachment to the uterus [4]. Our hypothesis is that Ang-(1–7) exerts an important regulatory role on the endocannabinoid system in the decidualization process of early gestation. In order to uncover this role, Ang-(1–7) was infused locally into one decidualized uterine horn of a pseudopregnant rat and its effects on the expression of the endocannabinoid receptors, CB1R and CB2R, and the enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), and the enzyme metabolizing another endogenous endocannabinoid, 2arachidonoylglycerol (2-AG), monoacyl glycerol lipase (MAGL), were evaluated, together with other markers of decidualization
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