Leptin reduces apoptosis triggered by high temperature in human placental villous explants: the role of the p53 pathway

VILARINO GARCIA,TERESA; DUEÑAS, JOSE; PEREZ PEREZ, ANTONIO; GUADIX, PILAR; VARONE, CECILIA; PEREZ PEREZ, ANTONIO; GUADIX, PILAR; VARONE, CECILIA; TORO, AYELÉN R; MAYMO, JULIETA; SANCHEZ-MARGALET, VICTOR; TORO, AYELÉN R; MAYMO, JULIETA; SANCHEZ-MARGALET, VICTOR; VILARINO GARCIA,TERESA; DUEÑAS, JOSE

PLACENTA

W B SAUNDERS CO LTD

Lugar: Londres; Año: 2016 vol. 42 p. 106 - 113

0143-4004

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 produces abnormal expression of proteins in the p53 pathway and finally caspase-3 activacion. Moreover, leptin, produced by placenta, is known 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 temperature, as well as the molecular mechanisms underlying this effect. Fresh placental tissue was collected from normal pregnancies. Explants of placental villi were exposed to 37ºC, 40ºC and 42ºC during 3 h in the presence or absence of 10 nM leptin in DMEM-F12 medium. Western blotting and qRT-PCR was performed to analize the expression of p53 and downstream effector, Mdm2, p21, BAX and BCL-2 as well as the activated cleaved form of caspase-3. Phosphorylation of the Ser 46 residue on p53, the expression of Mdm2, p21, as well as caspase-3 were significantly increased in explants at 40ºC and 42ºC. Conversely, these effects were significantly attenuated by leptin 10 nM at both 40ºC and 42ºC. The BCL2/BAX ratio was also significantly decreased in explants at 40ºC and 42ºC compared with explants incubated at 37ºC, which was prevented by leptin stimulation. These data illustrate the potential role of leptin for inhibiting the excessive apoptosis in villous trophoblast triggered by high temperature, by preventing the activation of p53 signaling