Dose-dependent insulin-mediated regulation of AQP9 in Human placenta

CASTRO-PARODI MAURICIO; FARINA MARIANA; DIETRICH VALERIA; LEVI LORENA; IBARRA CRISTINA; DAMIANO ALICIA E

Los Cocos, Córdoba- Argentina

Simposio; III Latin-American Symposium on Maternal-Fetal Interaction and Placenta:Basic & Clinical Research; 2007

Placental Association of America

Preeclampsia (PE) is a hypertensive disorder associated with an altered placental villous angiogenesis that can affect the transport functions of the syncytiotrophoblast (hST). Human term placenta hST is a continuous multinucleated structure with minimal tight junctions. Thus, the transport of metabolites, ions, and water from mother to fetus could take place primarily via transcellular routes. Water transport across hST may be facilitated by aquaporins (AQPs). Previously we reported that in preeclamptic placentas AQP9 molecular expression is increased. AQP9 promoter gene contains a negative insulin response element (-TGTTTTC-) suggesting that it may be modulated by insulin. Recently, we observed in women who develop PE that plasma insulin concentration is augmented, and AQP9 protein is over expressed in hST. Objective: The aim of our work was to investigate if in human placentas insulin regulates AQP9 in a dose-dependent manner. Methods: Explants from normal term placentas were cultured at different concentration of insulin during 24 h. Treatment with TNF-a 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 AQP9 expression. Results: Insulin treatment produced dose-dependent decreases of AQP9 expression in hST. Explants treated with TNF-a and different insulin doses did not show changes in AQP9 expression. Conclusions: Our results suggest that in human placenta AQP9 regulation is mediated by insulin in a dose-dependent way. Moreover, in preeclamptic placentas it seems to be ineffective to down regulate AQP9 expression probably as a consequence of the immunological dysfunction that occurs in this syndrome.