Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology
Defective decidualization during and after severe preeclampsia reveals a possible maternal contribution to the etiology
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DOI：
10.1073/pnas.1706546114
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发表时间：
2017-10-03
影响因子：
11.1
通讯作者：
Simon, Carlos
中科院分区：
文献类型：
--
作者：
Garrido-Gomez, Tamara;Dominguez, Francisco;Simon, Carlos
在子痫前期（PE），细胞滋养细胞（CTB）侵入子宫和螺旋动脉通常是浅的。因此，胎盘的作用一直是一个焦点。在这项研究中，我们检验了蜕膜缺陷是胎盘表型的重要决定因素的假设。我们从伴有严重PE （sPE）的未怀孕供体中分离出人子宫内膜基质细胞。与对照细胞相比，通过形态学标准和阶段特异性抗原（即IGFBP1， PRL）的分析表明，它们在体外未能实现脱个体化。这些结果得到了全球转录分析数据的支持，表明它们在转录上是惰性的。此外，我们使用激光显微解剖从sPE的母胎界面组织切片中分离蜕膜。全球转录谱揭示了基因表达缺陷。此外，sPE患者的蜕细胞在体外去分化，在培养中不能再蜕细胞。来自这些细胞的条件培养基不能支持CTB的侵袭。为了模拟正常妊娠的子宫环境，我们添加了PRL和IGFBP1，增强了侵入性。这些数据表明，去个体化失败是sPE患者CTB侵袭下调的重要因素。未来的研究将旨在确定这一发现在评估女性发生妊娠并发症的风险方面是否具有转化潜力。
In preeclampsia (PE), cytotrophoblast (CTB) invasion of the uterus and spiral arteries is often shallow. Thus, the placenta's role has been a focus. In this study, we tested the hypothesis that decidual defects are an important determinant of the placental phenotype. We isolated human endometrial stromal cells from nonpregnant donors with a previous pregnancy that was complicated by severe PE (sPE). Compared with control cells, they failed to decidualize in vitro as demonstrated by morphological criteria and the analysis of stage-specific antigens (i.e., IGFBP1, PRL). These results were bolstered by global transcriptional profiling data that showed they were transcriptionally inert. Additionally, we used laser microdissection to isolate the decidua from tissue sections of the maternal-fetal interface in sPE. Global transcriptional profiling revealed defects in gene expression. Also, decidual cells from patients with sPE, which dedifferentiated in vitro, failed to redecidualize in culture. Conditioned medium from these cells failed to support CTB invasion. To mimic aspects of the uterine environment in normal pregnancy, we added PRL and IGFBP1, which enhanced invasion. These data suggested that failed decidualization is an important contributor to down-regulated CTB invasion in sPE. Future studies will be aimed at determining whether this discovery has translational potential with regard to assessing a woman's risk of developing this pregnancy complication.