Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall
Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall
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DOI：
10.1016/s0002-9440(10)65123-1
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发表时间：
1999-07-01
影响因子：
6
通讯作者：
Fisher, SJ
中科院分区：
文献类型：
--
作者：
DiFederico, E;Genbacev, O;Fisher, SJ
先兆子痫是一种严重的妊娠并发症，诊断为广泛的母体内皮功能障碍。在正常妊娠中，胎盘滋养细胞干细胞亚群执行一种不寻常的分化程序，导致子宫及其血管系统的侵袭。这一过程将胚胎附着在子宫壁上，并开始将母体血液流向胎盘。先兆子痫与细胞滋养细胞分化异常、浅表侵袭和胎盘血流量减少有关。为了确定分化异常和/或缺氧是否导致细胞滋养层细胞凋亡，我们使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)方法标记了胎盘及其附着的子宫壁组织切片中的DNA链断裂。对照组(n=9)几乎未见细胞凋亡，而子痫前期组(n=9)有15-50%侵入子宫壁的细胞滋养细胞被标记。这些细胞没有表达Bcl2，这是一种通常由胎盘和子宫壁的滋养层细胞表达的生存因子。我们的结果表明，子痫前期与侵入子宫的细胞滋养层细胞的广泛凋亡有关。这一人群中程序性细胞死亡的程度可能是某些患者突然出现症状以及相关凝血障碍的原因。
Preeclampsia is a serious pregnancy complication diagnosed by signs of widespread maternal endothelial dysfunction. In normal pregnancy, a subpopulation of placental cytotrophoblast stem cells executes an unusual differentiation program 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. Preeclampsia is associated with abnormal cytotrophoblast differentiation, shallow invasion, and decreased blood flow to the placenta. To determine whether abnormal differentiation and/or hypoxia leads to cytotrophoblast apoptosis, we used the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) 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 almost no apoptosis, but in samples from patients with preeclampsia, 15-50% of the cytotrophoblasts that invaded the uterine wall were labeled (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 preeclampsia 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.