CONICET | Buscador de Institutos y Recursos Humanos

Normal fetal growth and development is critically dependent on sufficient transport of nutrients, metabolites, ions and water across the placenta. The syncytiotrophoblast of term human placenta (hST) is a continuous multinucleated structure with minimal tight junctions, which results from the fusion of the underlying cytotrophoblast cells. Thus, the transport of metabolites, ions and water from mother to fetus could take place primarily via transcellular routes. Transcellular water transport across hST may be facilitated by aquaporins (AQPs). We previously observed an increase of AQP9 expression in preeclamptic placenta with a lack of functionality of AQP9 for water and mannitol. We also observed high serum levels of insulin in Preeclamptic women. There is strong evidence that cystic fibrosis transmembrane conductance regulator (CFTR) regulates the AQP9 functionality. We observed that CFTR localizes in the apical plasma membrane in normal placentas, but it decreases in preeclamptic placentas where there AQP9 is significantly augmented.Explants from normal term placentas were cultured at different concentration of insulin during 24 h. Treatment with TNF-alfa was used to induce serine/threonine phosphorylation of insulin receptor resulting in a desensitization of insulin action. Western blot assays and immunohistochemistry were used to quantify CFTR expression.RESULTS: Insulin treatment produced dose-dependent decreases of CFTR expression in hST. Explants treated with TNF-alfa and insulin 100 uI/mL showed no changes in CFTR expression possibly due to the insulin-receptor phosphorilation. Conclusions: Our results suggest that insulin may play a role in the CFTR expression in human placenta. High levels of insulin may be implicated in the lack of CFTR expression. However, the molecular mechanisms are not clarified yet. Futhrer more studies are needed to elucidate them.

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