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Human Reproduction, Vol. 14, No. suppl_2, pp. 59-66, 1999
© 1999 European Society of Human Reproduction and Embryology

Invasive cytotrophoblast apoptosis in pre-eclampsia

Olga Genbacev1, Elaine DiFederico2, Mike McMaster2 and Susan J. Fisher1,2,3,4,5

1 Department of Stomatology San Francisco, San Francisco, CA 94143, USA 2 Department of Obstetrics, Gynecology and Reproductive Sciences San Francisco, San Francisco, CA 94143, USA 3 Department of Pharmaceutical Chemistry San Francisco, CA 94143, USA 4 Department of Anatomy, University of California San Francisco San Francisco, CA 94143, USA

Correspondence: 5To whom correspondence should be addressed at: HSW 604, University of California San Francisco, San Francisco, CA 94143–0512, USA

Pre-eclampsia is a serious pregnancy complication diagnosed by signs of widespread maternal endothelial dysfunction. In normal pregnancy, a subpopulation of placental cytotrophoblast stem cells executes a differentiation programme that leads to invasion of the uterus and its vasculature. This process attaches the conceptus to the uterine wall and starts the flow of maternal blood to the placenta. In pre-eclampsia, cytotrophoblasts fail to differentiate along the invasive pathway. The functional consequences of this abnormality negatively affect interstitial and endovascular invasion, thereby compromising blood flow to the maternal–fetal interface. To determine whether abnormal differentiation and/or hypoxia leads to apoptosis of invasive cytotrophoblasts, we used the TUNEL (terminal deoxynucleotidyl transferase-mediated 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 samples from patients with pre-eclampsia, 15–50% of the cytotrophoblast subpopulation 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 trophoblasts in both the placenta and the uterine wall. Our results show that pre-eclampsia is associated with widespread apoptosis of cytotrophoblasts that invade the uterus. The magnitude of programmed cell death in this population may account for the sudden onset of symptoms in some patients, as well as the associated coagulopathies.

Key words: apoptosis/Bcl-2/cytotrophoblast/placenta/pre-eclampsia


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