Preeclampsia (PE) is an obstetric disorder with significant morbidities for both the mother and fetus possibly caused by a failure of the placental trophoblast invasion. However, its pathophysiology largely remains unclear. Here, we performed DNA methylation profiling to determine whether differential patterns of DNA methylation correlate with PE and severe features of PE. We extracted DNA from placental tissues of 13 normal, five PE, and eight PE pregnant women with severe features. Genome-wide DNA methylation analysis was performed using the Illumina HumanMethylation 850K BeadChip. New functional annotations of differentially methylated CpGs (DMCs) in PE were predicted using bioinformatics tools. Significant differences were evident for 398 DMCs, including 243 DMCs in PE and 155 DMCs in PE with severe features, compared with normal placental tissues. Of these, 12 hypermethylated DMCs and three hypomethylated DMCs were observed in both PE groups, thus were independent from severe features. Three hundred seventy-nine DMCs were identified by the presence or absence of severe features. Two hundred genes containing these DMCs were associated with developmental processes and cell morphogenesis. These genes were significantly associated with various PE complications such as disease susceptibility, viral infections, immune system diseases, endocrine disturbance, seizures, hematologic diseases, and thyroid diseases. This is the first study to investigate the genome-scale DNA methylation profiles of PE placentas according to severe features. The epigenetic variation in the placentas probably resulted in altered developmental processes and immune dysregulation, contributing to PE. This study provides basic information to refine the clinical and pathological mechanisms of the severe features in placenta-mediated PE.

中文翻译：

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根据严重特征对先兆子痫胎盘进行表观基因组范围的 DNA 甲基化分析。

先兆子痫 (PE) 是一种产科疾病，对母亲和胎儿都有显着的发病率，可能是由于胎盘滋养细胞侵袭失败引起的。然而，其病理生理学在很大程度上仍不清楚。在这里，我们进行了 DNA 甲基化分析，以确定 DNA 甲基化的差异模式是否与 PE 和 PE 的严重特征相关。我们从 13 名正常、5 名 PE 和 8 名具有严重特征的 PE 孕妇的胎盘组织中提取 DNA。使用 Illumina HumanMethylation 850K BeadChip 进行全基因组 DNA 甲基化分析。使用生物信息学工具预测 PE 中差异甲基化 CpG (DMC) 的新功能注释。398 个 DMC 存在显着差异，包括 PE 中的 243 个 DMC 和 PE 中具有严重特征的 155 个 DMC，与正常胎盘组织相比。其中，在两个 PE 组中均观察到 12 个高甲基化 DMC 和 3 个低甲基化 DMC，因此与严重特征无关。379 个 DMC 通过严重特征的存在与否来识别。含有这些 DMC 的 200 个基因与发育过程和细胞形态发生有关。这些基因与各种 PE 并发症显着相关，例如疾病易感性、病毒感染、免疫系统疾病、内分泌紊乱、癫痫、血液系统疾病和甲状腺疾病。这是第一项根据严重特征调查 PE 胎盘基因组规模 DNA 甲基化谱的研究。胎盘的表观遗传变异可能导致发育过程的改变和免疫失调，为PE做出贡献。本研究为完善胎盘介导的 PE 严重特征的临床和病理机制提供了基础信息。