CEFYBO   02669
CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Anandamide and Cyclooxigenase-2 Regulate Uterine Stromal Fibroblasts Behavior
Autor/es:
SORDELLI, MS; RIBEIRO, ML; CAÑUMIL, VA; FRANCHI, AM; BELTRAME, JS; MERESMAN G
Lugar:
París
Reunión:
Congreso; Society for Reproductive Investigation; 2019
Resumen:
Anandamide (AEA) is a lipid mediator from the group of endocannabinoids that participates in embryo implantation. AEA tone is regulated by its degrading enzyme, fatty acid amide hydrolase (FAAH) and dysregulations in AEA production are correlated with implantation failure and recurrent abortion. Also, cyclooxigenase-2 derived prostaglandins play a crucial role at implantation sites. During early pregnancy the endometrial stroma is mainlyformed by fibroblasts, and later when embryo invasion begins, these fibroblasts develop into decidual cells. Yet, the role of stromal fibroblasts during early gestation remains unexplored. It has been described that anandamide and prostaglandins regulate fibroblast behavior in many biological systems.Using in vitro and in vivo models we investigated the action of anandamide in stromal fibroblasts behavior at the maternal?fetal interface. As day 5 pregnant rat uterus (day of implantation) is principally composed by stromal fibroblasts, Wistar females were sacrificed in this day of gestation. Uterine horns were excised and incubated for 1 h with AEA 1 nM alone or in the presence of indomethacin (a non-selective cyclooxigenase-1 and 2inhibitor) or meloxicam (a highly selective cyclooxigenase-2 inhibitor). We determined the production of prostaglandins by radioimmunoassay. For the in vivo approach, rats in day 5 of gestation received an intra-uterine injection of URB-597 (a FAAH selective inhibitor). Parameters related to implantation events and cyclooxigenase-2 protein level (western blot) were studied in day 8 of pregnancy. In order to validate the results in human stromal fibroblasts, T-hESC cells were seeded in 24 well plates, incubated for 12 h with AEA (1 nM - 1000 nM) or URB-597 (1 nM - 100 nM) and the percentage of wound healing was determined.AEA increased the production of prostaglandins E2 and F2 alpha (p