Protective effect of leptin on the apoptosis of trophoblast explants triggered by high temperature

PEREZ PEREZ, ANTONIO; AYELEN TORO; MAYMÓ, JULIETA; ISABEL CORRALES; JOSE LUIS DUEÑAS; CECILIA VARONE; SÁNCHEZ MARGALET, VICTOR

Mar del Plata

Congreso; Latin American Symposium on Maternal Fetal Interaction & Placenta; 2015

Maternal fever is common during pregnancy and has for many years been suspected to harm the developing fetus. Whether increased maternal temperature produces exaggerated apoptosis in trophoblast cells remains unclear. Since p53 is a critical regulator of apoptosis we hypothesized that increased temperature in placenta produce abnormal expression of proteins participating in the p53 pathway and finally Caspase-3 activation. Moreover, leptin, produced by placenta, has demonstrated to promote the proliferation and survival of trophoblastic cells. That is why we aimed to study the possible role of leptin preventing apoptosis triggered by high temperatures, as well as the molecular mechanisms underlying this effect. Fresh placental tissue was collected from normal pregnancies. Placental explants were exposed to increased temperature (40ºC and 42ºC) for different time points in the presence or absence of 10 nM leptin. Western blotting was performed on tissue lysate for protein expression of p53 and downstream effector proteins: p21, Bax, Mdm-2 and Caspase-3. Maximal apoptotic effect of high temperature was observed after 3 h incubation of trophoblasts. Protein expression of p53, p21, Bax, Mdm-2 and Caspase-3 were significantly increased in explants at 40ºC and 42ºC in compared with explants to 37ºC. Conversely, this increased expression was significantly attenuated by leptin 10 nM at both 40ºC and 42ºC. These data illustrate the potential role of leptin for inhibiting the excessive apoptosis in villous trophoblast triggered by high temperature. However, the upstream regulation of p53 with regard to exaggerated apoptosis in response to elevated temperature merits further investigation.