Role of leptin in the molecular physiology of the placenta

MALENA SCHANTON; AYELÉN TORO; PAULA BALESTRINI; JULIETA L. MAYMÓ; RIEDEL, RODRIGO; ANTONIO PÉREZ PÉREZ; BERNARDO MASKIN; VÍCTOR SÁNCHEZ-MARGALET; CECILIA L. VARONE

Simposio; VII SLIMP- Latin American Symposium on Maternal Fetal Interaction & Placenta; 2017

Role of leptin in the molecular physiology of the placentaMalena Schantona, Ayelén Toroa, Paula Balestrinia, Julieta Maymóa, Rodrigo Riedela, Antonio Pérez-Pérezb, Bernardo Maskinc, Víctor Sánchez-Margaletb and Cecilia VaroneaaDepartamento de Química Biológica, FCEN, UBA, IQUIBICEN CONICET, Buenos Aires, Argentina. bDepartamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Sevilla, España. cHospital Nacional Alejandro Posadas, Buenos Aires, ArgentinaLeptin is a key hormone in placental physiology. It regulates trophoblast proliferation, inhibits apoptosis, stimulates protein synthesis, and regulates fetal growth and development. Previous results demonstrated that estradiol (E2) regulates leptin expression.Objectives In the present study, we analyzed the effect of SP1 and cAMP signaling pathway in the induction of leptin expression by E2 in human placental cells. We also study the mechanisms that mediate the antiapoptotic effect of leptin in placenta and a possible role of leptin on cell migration and invasion. Methods: BeWo and Swan cells, cultured under standard conditions, and human placental explants were used. Western blot, qRT-PCR and transfection assays were carried out. All procedures were approved by ethical review committee at the A Posadas National Hospital.Results: We observed that SP1 and cAMP-PKA pathway increased leptin promoter activity. SP1 effect is ER dependent. The inhibitors H89 and SQ22536 and HDAC protein diminished E2 induction of leptin.We have demonstrated also that p53, is down-regulated in the presence of leptin under serum deprivation or hypoxia involving MAPK and PI3K signaling pathways. Leptin also augments the levels of Mdm2 protein, a regulator of p53 half life. On the other hand leptin reduced E-cadherin and induced β1 Integrin expression. Moreover wound healing assay and invasion assay demonstrated that leptin promotes cell migration and invasion. Conclusions: All these findings suggest that leptin expression is tightly regulated and improve the comprehension of the mechanisms whereby E2 regulates leptin expression and leptin function during pregnancy.