Placental Peroxisome Proliferator-Activated Receptor-γ Is Up-Regulated by Pregnancy Serum1

Lipid metabolism plays an important role in normal pregnancy adaptation and in pathological pregnancy (e.g. preeclampsia). In the current studies we examined the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in tissues and cells relevant to human pregnancy. We found that PPARgamma is expressed in placental cytotrophoblasts in vivo and in trophoblasts (primary and choriocarcinoma cells) and fetal endothelial cells in vitro. We characterized primary cytotrophoblasts and two cell lines with which to study PPARgamma regulation in human pregnancy. Like primary cytotrophoblasts, the choriocarcinoma cell line JEG-3 has endogenous PPARgamma expression. Normal positive and negative PPARgamma regulation was observed in the latter cells. We also created a new JEG-3-derived cell line (EP-JEG) by stable insertion of a PPAR response element-luciferase reporter gene construct. Together, these cell lines are useful for studying PPARgamma expression and activation in human trophoblasts. We examined PPARgamma regulation in these cells by human serum and found that PPARgamma protein expression and activation are dramatically increased by sera from pregnant women. Preliminary characterization of the regulatory principle(s) is consistent with a prostanoid or fatty acid derivative. The results suggest that increased activation of PPARgamma may play an important role in maternal metabolism during human pregnancy.