Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, 10000 Prague, Czech Republic.
Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, 14700 Prague, Czech Republic.
Int J Mol Sci. 2019 Feb 2;20(3):654. doi: 10.3390/ijms20030654.
Children descending from pregnancies complicated by gestational hypertension (GH), preeclampsia (PE) or fetal growth restriction (FGR) have a lifelong cardiovascular risk. The aim of the study was to verify if pregnancy complications induce postnatal alterations in gene expression of microRNAs associated with cardiovascular/cerebrovascular diseases. Twenty-nine microRNAs were assessed in peripheral blood, compared between groups, and analyzed in relation to both aspects, the current presence of cardiovascular risk factors and cardiovascular complications and the previous occurrence of pregnancy complications with regard to the clinical signs, dates of delivery, and Doppler ultrasound examination. The expression profile of miR-21-5p differed between controls and children with a history of uncomplicated pregnancies with abnormal clinical findings. Abnormal expression profile of multiple microRNAs was found in children affected with GH (miR-1-3p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, and miR-342-3p), PE (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-103a-3p, miR-133a-3p, miR-342-3p), and FGR (miR-17-5p, miR-126-3p, miR-133a-3p). The index of pulsatility in the ductus venosus showed a strong positive correlation with miR-210-3p gene expression in children exposed to PE and/or FGR. Any of changes in epigenome (up-regulation of miR-1-3p and miR-133a-3p) that were induced by pregnancy complications are long-acting and may predispose children affected with GH, PE, or FGR to later development of cardiovascular/cerebrovascular diseases. Novel epigenetic changes (aberrant expression profile of microRNAs) appeared in a proportion of children that were exposed to GH, PE, or FGR. Screening of particular microRNAs may stratify a highly risky group of children that might benefit from implementation of early primary prevention strategies.
患有妊娠高血压（GH）、先兆子痫（PE）或胎儿生长受限（FGR）的儿童存在终生心血管风险。本研究旨在验证妊娠并发症是否会导致新生儿与心血管/脑血管疾病相关的 microRNA 表达发生后天变化。在 29 个 microRNA 在外周血中进行了评估，在组间进行了比较，并与心血管危险因素和心血管并发症的存在以及妊娠并发症的发生与临床发现、分娩日期和多普勒超声检查有关的情况进行了分析。在无并发症的妊娠中出现异常临床发现的儿童中，miR-21-5p 的表达谱与对照组不同。在患有 GH（miR-1-3p、miR-17-5p、miR-20a-5p、miR-21-5p、miR-23a-3p、miR-26a-5p、miR-29a-3p、miR-103a-3p、miR-125b-5p、miR-126-3p、miR-133a-3p、miR-146a-5p、miR-181a-5p、miR-195-5p 和 miR-342-3p）、PE（miR-1-3p、miR-20a-5p、miR-20b-5p、miR-103a-3p、miR-133a-3p、miR-342-3p）和 FGR（miR-17-5p、miR-126-3p、miR-133a-3p）的儿童中，发现多个 microRNA 的异常表达谱。脐静脉搏动指数与暴露于 PE 和/或 FGR 的儿童的 miR-210-3p 基因表达呈强正相关。由妊娠并发症引起的表观基因组（miR-1-3p 和 miR-133a-3p 的上调）的任何变化都是长效的，可能使患有 GH、PE 或 FGR 的儿童易患心血管/脑血管疾病。在暴露于 GH、PE 或 FGR 的儿童中，出现了一定比例的新的表观遗传变化（microRNA 的异常表达谱）。筛选特定的 microRNA 可能会对高危儿童进行分层，这些儿童可能受益于早期初级预防策略的实施。
