Abstract-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.
Variations of MicroRNAs in Human Placentas and Plasma From Preeclamptic Pregnancy
Xu et al Differential miRNAs in Preeclampsia 1277modulating effect of miR-18a. The data provide important evidences for exploring the pathogenesis of the disease from a noncoding RNA viewpoint.
Materials and MethodsAll the details of the materials and methods are provided in the online-only Data Supplement.
Study SubjectsIn this study, the collection of human placenta tissues and plasma specimens was performed with the permission of the local ethical committee in the Institute of Zoology, Chinese Academy of Sciences, and informed consent was obtained from all patients enrolled in this study. Placentas and maternal blood samples from normal pregnant and preeclamptic women were obtained from pregnant women who underwent perinatal care in Peking University Third Hospital from August 2010 to October 2012. Totally 20 severe preeclamptic patients who delivered at 35th to 39th weeks and 33 normal pregnant women who delivered at 37th to 39th weeks were enrolled in this study. Their placentas at deliveries and plasma samples at gestational weeks 15 to 18 and weeks 35 to 38 were used. The clinical characteristics of these women are summarized in Table 1.
miRNA Microarray AnalysisLarge-scale profiling of miRNA expression was achieved by mammalian miRNA chip array (V2.0, Capitalbio, Beijing, China), which stems from the miRbase release 8.2 (Wellcome Trust Genome Camp...
