Role of leptin in the molecular physiology of the placenta

SCHANTON, MALENA; MAYMÓ, JULIETA; MASKIN, BERNARDO; BALESTRINI, PAULA; PEREZ PEREZ, ANTONIO; VARONE, CECILIA; TORO, AYELEN; RIEDEL, RODRIGO; SANCHEZ-MARGALET, VICTOR

Puerto Varas

Congreso; Latin American Symposium on Maternal Fetal Interaction & Placenta; 2017

Leptin is a key hormone in placental physiology. It regulates trophoblast proliferation,inhibits apoptosis, stimulates protein synthesis, and regulates foetal growth and development. Previous results demonstrated that estradiol (E2) regulates leptin expression. Objectives: We analysed the effect of specific protein 1 (SP1) and cAMP signalling 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 leptinon 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 counted with the approval from the Ethical review committee of the Hospital Nacional Alejandro Posadas. Results: We observed that SP1 and cAMPproteinkinase A pathway increased leptin promoter activity. SP1 effect is oestrogenreceptor alpha (ERa) dependent. The inhibitors H89 and SQ22536, and HDACprotein diminished E2 induction of leptin. We have demonstrated also that p53, is downregulated in the presence of leptin under serum deprivation or hypoxia involving mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase (PI3K) signalling pathways. Leptin also augments the level of Mdm2 protein, a regulator of p53 half-life. On the other handleptin 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.