Article ID Journal Published Year Pages File Type
2195980 Molecular and Cellular Endocrinology 2015 9 Pages PDF
Abstract

•Cytotrophoblasts and syncytiotrophoblast express 2-AG main metabolic enzymes.•2-AG impairs functional and morphological differentiation of human cytotrophoblasts.•2-AG effects are mediated by the activation of cannabinoid receptors.•2-AG effects may result from the inhibition of cAMP/PKA signalling pathway.

A 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.

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