In vivo and in vitro evidence for placental DNA damage in preeclampsia.

Preeclampsia (PE) is an idiopathic multisystem disease affecting 5-7% of pregnant women. Placental oxidative stress is a characteristic feature of PE and occurs when the production of reactive oxygen species (ROS) within the placenta overwhelms the intrinsic anti-oxidant defenses. We hypothesize that excessive oxidative DNA damage at the fetal-maternal interface coupled with a defective DNA damage/repair response is causally related to PE. Here we demonstrate that γH2AX (a sensitive marker of DNA damage) is expressed in the maternal decidua but not trophoblast of normal placentas, and that expression is significantly higher in PE placental tissues in vivo. Using primary in vitro cultures of maternal decidual stromal cells (DSCs) and fetal cytotrophoblast cells (CTs), we show an increase in γH2AX foci in DSCs cultured with vs without H2O2 (70.6% vs 11.6%; P