Effect of leptin on the apoptosis of trophoblast explants triggered by acidosis

PEREZ PEREZ, ANTONIO; TORO, AYELEN; VILARINO GARCIA,TERESA; MAYMÓ, JULIETA; VARONE, CECILIA; SANCHEZ-MARGALET, VICTOR

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2016

Decrease in gas exchange at the level of the placenta is a serious complication during pregnancy. Disturbance pH of the internal environment can alter fetal, maternal and placental functions. In particular, the decrease in pH can alter the fetal tissue homeostasis causing irreparable fetal death or damage by metabolic acidosis. In this context we decided to study the effect of lowering the pH on the apoptotic process in placental explants and leptin action under such conditions. Based on previous results of our research group and the central role of p53 in the regulation of apoptosis, we hypothesize that pH changes in the placental cells increase apoptosis by altering the expression of p53 as well as their target genes. In this context we investigated the possible antiapoptotic effect of leptin in trophoblast cells subjected to different pHs.Human placental explants at term were incubated in DMEM F-12 at different pH (7.4, 7 and 6.8) in the presence or absence of 10 nM leptin. p53 levels and its downstream effectors p21, BAX and BCL-2, as well as the cleaved fragment of PARP-1 and the active form of caspase-3 were analyzed by Western blot and qRT-PCR. We found an increase in p53 phosphorylation (Ser 46), p21 and PARP-1 expressions and activation of caspase-3 in the explants incubated at pH 7 and 6.8. Conversely, these effects were attenuated in the presence of 10 nM leptin both pH 7 and pH 6.8. The BCL-2 / BAX ratio decreased at pH 7 and 6.8 compared with explants incubated at pH 7.4, and this effect was counteracted by treatment with leptin.These data demonstrate a potential anti-apoptotic effect of leptin involving the regulation of p53 axis in placental explants cultured at acidic pHs, suggesting that placental leptin has a protective effect on trophoblast cells.