Role of leptin in the molecular physiology of the placenta

MALENA SCHANTON; AYELÉN TORO; PAULA BALLESTRINI; JULIETA MAYMÓ; RODRIGO RIEDEL; ANTONIO PÉREZ-PÉREZ; BERNARDO MASKIN; VICTOR SÁNCHEZ MARGALET; CECILIA VARONE

Puerto Varas

Congreso; Simposio Latinoamericano de Interacción Materno Fetal (SLIMP); 2017

SLIMP

Leptin is a key hormone in placental physiology. It regulates trophoblastproliferation, inhibits apoptosis, stimulates protein synthesis, and regulatesfoetal growth and development. Previous results demonstrated thatestradiol (E2) regulates leptin expression.Objectives: We analysed the effect of specific protein 1 (SP1) and cAMPsignalling pathway in the induction of leptin expression by E2 in humanplacental cells. We also study the mechanisms that mediate the antiapoptoticeffect of leptin in placenta and a possible role of leptinon cellmigration and invasion.Methods: BeWo and Swan cells, cultured under standard conditions, andhumanplacental explants were used.Western blot, qRT-PCR and transfectionassays were carried out. All procedures counted with the approval from theEthical review committee of the Hospital Nacional Alejandro Posadas.Results: We observed that SP1 and cAMP-protein kinase A pathwayincreased leptin promoter activity. SP1 effect is oestrogen receptor alpha(ERa) dependent. The inhibitors H89 and SQ22536, and HDAC proteindiminished E2 induction of leptin. We have demonstrated also that p53, isdownregulated in the presence of leptin under serum deprivation orhypoxia involving mitogen-activated protein kinases (MAPK) and phosphatidylinositol-3-kinase(PI3K) signalling pathways. Leptin also augmentsthe level of Mdm2 protein, a regulator of p53 half-life. On the otherhandleptin reduced E-cadherin and induced b1 integrin expression.Moreover wound healing assay and invasion assay demonstrated thatleptin promotes cell migration and invasion.Conclusions: All these findings suggest that leptin expression is tightlyregulated and improve the comprehension of the mechanisms whereby E2regulates leptin expression and leptin function during pregnancy