Anandamide regulates vascular adaptations at the maternal-fetal interface in the rat

CAÑUMIL, VA; BELTRAME JS; SCHEFFER FRIDA; DE LA CRUZ BORTHIRY, FL; BOGETTI E; FRANCHI, AM; MERESMAN G; RIBEIRO, ML

Congreso; X Virtual Meeting Of The Latin American Society Of Maternal-Fetal Interaction And Placenta (SLIMP) 2022; 2022

Aim: Successful implantation and placentation requires vascular transformation of the uterus.Anandamide (AEA) is a potent lipid mediator that regulates embryo implantation and many ofthe placental functions. However, its role in uterine vascular transformations at early gestationremains unknown. Therefore, the aim of this work was to investigate the relevance of AEA invascular adaptations that occur in the uterus at the time of embryo implantation. Also, weevaluated ciclooxigenase-2 (COX-2) participation. COX is the rate limiting enzyme in thesynthesis of prostaglandins, which are angiogenic mediators in mice implantation sites.Methodology: Wistar females received an intrauterine injection of URB-597 in day 5 of gestation(day of implantation). URB-597 is a highly selective inhibitor of fatty acid amide hydrolase(FAAH), AEA degrading enzyme. URB-597 is used as a pharmacological tool to increase AEAlevel. The contralateral horn was treated with vehicle (control). A group of rats were injected with meloxicam i.p. (a highly selective COX-2 inhibitor) 2 h before URB-597. Animals wereeuthanized in day 8 of gestation. Uterine horns were photographed and vascular andhistological analyzes were performed.Results: URB-597 augmented the diameter of the uterine and arcuate arteries. Theseobservations were accompanied by an increase in fetal resorptions, aberrant embryo spacing,abortions and an increase in the thickness of the uterine smooth muscle. When evaluatinguterine microvasculature, we observed that the number of vessels in the resorbed implantationsites was significantly higher compared to control units. The wall:lumen ratio of the vessels and the decidua was not modified. Besides, URB-597 increased the expression of COX-2 inresorbed implantation sites. The treatment with meloxicam prevented all the effects describedfor URB- 597.Conclusion: Our results suggest a new role for AEA in the vascular adaptations at the maternal-fetal interface during early gestation by a mechanism that involves COX-2 isoform.