Correspondence and reprint requests to Yan-ling Wang or Lei Ji, State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Rd, Chaoyang District, Beijing 100101, People's Republic of China.
Hypertension. 2014 Jun;63(6):1276-84. doi: 10.1161/HYPERTENSIONAHA.113.02647. Epub 2014 Mar 24.
Preeclampsia is a major cause of maternal and fetal mortality and morbidity worldwide. The differential expression of several microRNAs (miRNAs) has been found in preeclamptic placentas. However, great conflict exists regarding this aspect, and detailed examinations have largely been lacking of miRNA profiles in different parts of the placenta and in maternal plasma of women with this disorder. In this study, a total of 9 downregulated miRNAs (miR-195, miR-223, miR-218, miR-17, miR-18a, miR-19b1, miR-92a1, miR-379, and miR-411) and 7 upregulated miRNAs (miR-210, miR-30a-3p, miR-518b, miR-524, miR-17-3p, miR-151, and miR-193b) were identified in severe preeclampsia (sPE) placentas when compared with normal pregnant controls. In addition, sampling position in the chorionic or basal plate of placenta led to evident variations in differential miRNAs of sPE placentas. In a prospective pregnant cohort, we found that the circulating levels of 3 members of miR-17-92 cluster (ie, miR-18a, miR-19b1, and miR-92a1) were significantly lower, whereas that of miR-210 was higher in sPE patients than those in normal controls at gestational weeks 15 to 18 and at term. The results of in situ hybridization revealed the localization of miR-18a, miR-92a1, and miR-210 in various subtypes of placental trophoblasts and endothelial cells. In human trophoblast cell line, HTR8/SVneo cells, miR-18a could promote trophoblast cell invasion via targeting and suppressing Smad2 expression. This study provides fundamental evidences for exploring the roles of miRNAs in the pathogenesis of preeclampsia.
子痫前期是全球孕产妇和胎儿死亡和发病的主要原因。在子痫前期胎盘组织中发现了几种微小 RNA（miRNA）的差异表达。然而，这方面存在很大的争议，并且对该疾病患者胎盘不同部位和母体外周血中 miRNA 谱的详细检查还很大程度上缺乏。在这项研究中，与正常妊娠对照组相比，在严重子痫前期（sPE）胎盘组织中发现了 9 个下调 miRNA（miR-195、miR-223、miR-218、miR-17、miR-18a、miR-19b1、miR-92a1、miR-379 和 miR-411）和 7 个上调 miRNA（miR-210、miR-30a-3p、miR-518b、miR-524、miR-17-3p、miR-151 和 miR-193b）。此外，胎盘绒毛膜或基底板的采样位置导致 sPE 胎盘差异 miRNA 出现明显变化。在一项前瞻性孕妇队列研究中，我们发现循环 miR-17-92 簇的 3 个成员（即 miR-18a、miR-19b1 和 miR-92a1）的水平在 sPE 患者中明显低于正常对照组，而 miR-210 的水平在妊娠 15 至 18 周和足月时均高于正常对照组。原位杂交的结果显示 miR-18a、miR-92a1 和 miR-210 定位于各种胎盘滋养层细胞和内皮细胞亚型中。在人滋养层细胞系 HTR8/SVneo 细胞中，miR-18a 通过靶向和抑制 Smad2 表达促进滋养层细胞侵袭。这项研究为探讨 miRNA 在子痫前期发病机制中的作用提供了基础证据。
