Costa, M. A.Keating, E.Fonseca, B. M.Teixeira, N. A.Correia-da-Silva, G.2015-05-112015-05-112015COSTA, M. A… [et al.] - 2-Arachidonoylglycerol impairs human cytotrophoblast cells syncytialization: Influence of endocannabinoid signalling in placental development. Molecular and Cellular Endocrinology. ISSN 0303-7207. Vol. 399 (2015), p. 386-940303-7207http://hdl.handle.net/10400.14/17535A balanced cytotrophoblast cell turnover is crucial for placental development and anomalies in this process associated with gestational diseases. The endocannabinoid system (ECS) has emerged as a new player in several biological processes. However, its influence during placental development is still unknown. We report here the expression of the endocannabinoid 2-arachidonoylglycerol (2-AG) main metabolic enzymes in human cytotrophoblasts and syncytiotrophoblast. We also showed that 2-AG induced a decrease in placental alkaline phosphatase activity, human chorionic gonadotropin secretion and Leptin mRNA levels. Moreover, 2-AG reduced glial cell missing 1 and syncytin-2 transcription and the number of nuclei in syncytium. These effects were mediated by cannabinoid receptors and may result from 2-AG inhibition of the cAMP/PKA signalling pathway. Our data suggest that 2-AG may interfere with the biochemical and morphological differentiation of human cytotrophoblasts, through a CB receptor-dependent mechanism, shedding light on a role for the ECS in placental development.eng2-arachinoylglycerolEndocannabinoid signallingHuman cytotrophoblastsSyncytializationPlacentajournal article10.1016/j.mce.2014.09.0058491201761525199616000348877700041