Invasive cytotrophoblast apoptosis in pre-eclampsia

Pre-eclampsia is a serious pregnancy complication diagnosed by signs of-wid espread maternal endothelial dysfunction, In normal pregnancy, a subpopulat ion of placental cytotrophoblast stem cells executes a differentiation prog ramme that leads to invasion of the uterus and its vasculature, This proces s attaches the conceptus to the uterine wall and starts the how of maternal blood to the placenta. In pre-eclampsia, cytotrophoblasts fail to differen tiate along the invasive pathway. The functional consequences of this abnor mality negatively affect interstitial and endovascular invasion, thereby co mpromising blood flow to the maternal-fetal interface. To determine whether abnormal differentiation and/or hypoxia leads to apoptosis of invasive cyt otrophoblasts, we used the TUNEL (terminal deoxynucleotidyl transferase-med iated dUTP nick end labelling) method to label DNA strand breaks in tissue sections of the placenta and the uterine wall to which it attaches. Control samples (n = 9) showed little or no apoptosis in any location, but in samp les from patients with pre-eclampsia, 15-50% of the cytotrophoblast subpopu lation that invaded the uterine wall was labelled (8/9 samples). These same cells failed to stain for Bcl-2, a survival factor normally expressed by t rophoblasts in both the placenta and the uterine wall. Our results show tha t pre-eclampsia is associated with widespread apoptosis of cytotrophoblasts that invade the uterus, The magnitude of programmed cell death in this pop ulation may account for the sudden onset of symptoms in some patients, as w ell as the associated coagulopathies.