ROLE OF LEPTIN ON THE APOPTOSIS OF TROPHOBLAST EXPLANTS TRIGGERED BY ACIDOSIS

RODRIGO RIEDEL; CECILIA VARONE; ANTONIO PÉREZ-PÉREZ; JULIETA MAYMÓ; VICTOR SÁNCHEZ MARGALET; TERESA VILARIÑO; MALENA SCHANTON

Buenos Aires

Congreso; International Federation of Placenta Associations 2019 (IFPA2019) and 8th Latin American Symposium on Maternal-Fetal Interaction and Placenta (VIII SLIMP); 2019

IFPA

Objectives: To study the effect of lowering the pH of the process ofapoptosis in placental explants and leptin action under such conditions.Based on previous results of our research group and the central role ofp53 in the regulation of apoptosis, we hypothesize that pH changes inthe placental cells increase apoptosis by altering the expression of p53as well as their target genes. In this context we investigated the possibleantiapoptotic effect of leptin in trophoblast cells subjected to differentpHsMethods: Explants human placenta at term were incubated in DMEM F-12at different pH (7.4, 7 and 6.8) in the presence or absence of 10 nM leptin.They were analyzed by Western blot and qRT-PCR p53 levels and itsdownstream effectors p21, BAX and BCL-2, as well as the cleaved fragmentof PARP-1 and the active form of caspase-3.Results: We found an increase in phosphorylation (Ser 46) p53 and p21expression, PARP-1 and activation of caspase-3 in the explants incubatedat pH 7 and 6.8. Conversely, these effects were attenuated in the presenceof 10 nM leptin both pH 7 and pH 6.8. The BCL-2 / BAX ratio decreased topH 7 and 6.8 compared with explants incubated at pH 7.4, an effect that iscounteracted by treatment with leptin.Conclusion: These data demonstrate an anti-apoptotic effect of leptinpotential involving the regulation of p53 axis explants cultured placentalacidic pHs, suggesting that placental leptin has a protective effect ontrophoblast cells