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- Transient receptor potential vanilloid 1 is expressed in human cytotrophoblasts: Induction of cell apoptosis and impairment of syncytializationPublication . Costa, M. A.; Fonseca, B. M.; Keating, E.; Teixeira, N. A.; Correia-da-Silva, G.The normal development of placenta relies essentially on a balanced proliferation, differentiation andapoptosis of cytotrophoblasts. These processes are tightly regulated by several hormones, cytokines,lipids and other molecules and anomalies in these events are associated with gestational complications.The cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed in several organs andtissues and it participates in cellular events like nociception, inflammation and cell death. However, theexpression and importance of this receptor in human placenta still remains unknown. In this work, wefound that TRPV1 is expressed in human cytotrophoblasts and syncytiotrophoblasts. Furthermore, theTRPV1 agonists capsaicin and anandamide decreased cytotrophoblast viability and induced morpho-logical alterations, such as chromatin condensation and fragmentation, which suggest the occurrenceof apoptosis. Also, both TRPV1 agonists induced a loss of mitochondrial membrane potential and anincrease of caspase 3/7 activity and production of reactive species of oxygen and nitrogen. Furthermore,capsaicin (10 M) impaired the spontaneous in vitro differentiation of cytotrophoblasts into syncytiotro-phoblasts by triggering TRPV1, as observed by the decrease in placental alkaline phosphatase activity andin human chorionic gonadotropin secretion. On the other hand, anandamide decreased placental alkalinephosphatase activity via a TRPV1-independent mechanism but did not influence the secretion of humanchorionic gonadotropin. In conclusion, we showed that TRPV1 is expressed in human cytotrophoblastsand syncytiotrophoblasts and also reported the involvement of this receptor in cytotrophoblast apoptosisand differentiation.
- 2-Arachidonoylglycerol impairs human cytotrophoblast cells syncytialization: influence of endocannabinoid signalling in placental developmentPublication . Costa, M. A.; Keating, E.; Fonseca, B. M.; Teixeira, N. A.; Correia-da-Silva, G.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.