Invasive cytotrophoblast apoptosis in pre-eclampsia
Invasive cytotrophoblast apoptosis in pre-eclampsia
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DOI：
10.1093/humrep/14.suppl_2.59
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发表时间：
1999-12-01
影响因子：
6.1
通讯作者：
Fisher, SJ
中科院分区：
文献类型：
--
作者：
Genbacev, O;DiFederico, E;Fisher, SJ
先兆子痫是一种严重的妊娠并发症，通过广泛的母体内皮功能障碍的症状来诊断。在正常妊娠中，胎盘细胞滋养层干细胞的亚群执行分化程序，导致子宫及其脉管系统的侵入。这个过程将概念附着在子宫壁上，并开始将母体血液输送到胎盘。在先兆子痫中，细胞滋养细胞无法沿着侵入途径分化。这种异常的功能后果会对间质和血管内侵袭产生负面影响，从而损害母胎界面的血流。为了确定异常分化和/或缺氧是否导致侵袭性细胞滋养细胞凋亡，我们使用 TUNEL（末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记）方法来标记胎盘及其附着的子宫壁组织切片中的 DNA 链断裂。对照样本 (n = 9) 在任何位置都显示很少或没有细胞凋亡，但在先兆子痫患者的样本中，侵入子宫壁的 15-50% 的细胞滋养层亚群被标记（8/9 样本）。这些相同的细胞未能对 Bcl-2 进行染色，Bcl-2 是一种通常由胎盘和子宫壁中的滋养层细胞表达的生存因子。我们的研究结果表明，先兆子痫与侵入子宫的细胞滋养细胞的广泛凋亡有关。该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病的原因。
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 how 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.