LEPTIN IS INVOLVED IN SURVIVAL AND IMMUNOMODULATION OF PLACENTAL CELLS. REGULATION OF ITS EXPRESSION

JULIETA L. MAYMÓ; YÉSICA GAMBINO; ANTONIO PÉREZ-PÉREZ; JOSÉ DUEÑAS; BERNARDO MASKIN; SANDRA BLOIS; JUAN CARLOS CALVO; VÍCTOR SÁNCHEZ-MARGALET; CECILIA L. VARONE

Foz de Iguazú

Simposio; Latin American symposium on maternal fetal interaction and placenta; 2013

Leptin is involved in survival and immunomodulation of placental cells. Regulation of its expression A Toroa, Y Gambinoa, J Maymóa, G Barrientosa, A Pérez-Pérezb, B Maskinc, SM Bloisd, JC Calvoa,V Sánchez-Margaletb and C Varonea aDepto. de Química Biológica, FCEN UBA, IQUIBICEN CONICET, Buenos Aires, Argentina. bDepto. de Bioquímica Médica y Biología Molecular. Universidad de Sevilla, Sevilla, España. cHospital Nacional A Posadas, Buenos Aires, Argentina. dDepto. De Medicina Interna, Universidad de Medicina Charité, Berlín, Alemania. Background: Leptin produced by the placenta has many roles as an autocrine hormone. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work we aimed to study the mechanisms that mediate the antiapoptotic effect of leptin in placenta. We determined whether leptin modulates HLA-G isoforms expression on placental cells, and also studied the regulation of transcriptional leptin expression. Methods: BeWo and Swan cells, cultured under standard conditions, as well as human placental explants were used. Western blot, qRT-PCR and transfection assays with reporter constructs and expression vectors were carried out. All procedures were approved by ethical review committee at the A Posadas National Hospital. Results: Leptin reduced the expression of p53, a key regulator of cell cycle, involving MAPK signaling pathway. Leptin also stimulated the expression of HLA-G1 on BeWo and placental explants. Leptin induction by estradiol is modulated by CREB, NFkB, Sp1 and AP1 transcription factors. Finally we found that the alternative Epac/cAMP pathway and the MAPK pathway mediate hCG induction of leptin expression in placental cells Conclusions: All these findings suggest that leptin expression is tightly regulated. Our results support the importance of leptin in the biology of reproduction. Key words: leptin-placenta-gene expression- survival-immunomodulation Modality:  Poster