PPARγ expression in normal human placenta, hydatidiform mole and choriocarcinoma

Peroxisome proliferator-activated receptor (PPAR) γ belongs to a subclass of nuclear hormone receptors that execute their transcriptional functions as heterodimers with the retinoid X receptors (RXR). PPARγ plays a pivotal role in cellular differentiation. This study investigated PPARγ protein expression in normal human placentas, hydatidiform moles and choriocarcinoma, using immunohistochemical and Western blot analyses. In first trimester normal placenta, PPARγ was mainly localized in the nuclei of the villous cytotrophoblastic cells, whereas at term it was mainly localized in the nuclei of the syncytiotrophoblast. Extravillous cytotrophoblast of cell islands and cell columns also showed nuclear PPARγ immunostaining. A striking result was the altered expression patterns of PPARγ in pathological tissues; PPARγ showed a reduced immunostaining in the trophoblastic diseases. In hydatidiform moles, PPARγ was mainly localized in the nuclei of the trophoblastic collections of the pathological villi and in the extravillous trophoblastic cells, whereas in the choriocarcinoma, only a few trophoblastic cells showed weak PPARγ nuclear immunostaining. These findings suggest an involvement of PPARγ in trophoblast differentiation during normal placental development. The down-regulation of PPARγ expression in the gestational trophoblastic diseases analysed in this study provides a new insight into the progression of these pathologies.