Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain.
Department of Obstetrics and Gynecology, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain.
Int J Mol Sci. 2021 Dec 28;23(1):293. doi: 10.3390/ijms23010293.
In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.
在一项前瞻性研究中,对 34 周后进行多普勒超声检查的 48 例胎儿根据脑胎盘比(CPR)和估计胎儿体重(EFW)进行分类,分为生长正常的胎儿和晚期发生的胎儿生长受限(LO-FGR)胎儿。通过实时 PCR 验证了来自 LO-FGR 胎儿新生儿脐血中 miRNA 的过表达。此外,通过分析过表达途径、基因本体论和协同作用 miRNA 的优先级,对过表达 miRNA 的功能特征进行了研究。miR-25-3p、miR-185-5p 和 miR-132-3p 这三种 miRNA 在 LO-FGR 胎儿的脐血中显著过表达。途径和基因本体论分析显示,与心脏发育和神经元死亡相关的某些分子途径存在过度表达。此外,协同作用 miRNA 的优先级强调了 miR-185-5p 和 miR-25-3p 在与 LO-FGR 表型相关的胆固醇外排和饥饿反应中的重要性。评估 miR-25-3p;miR-132-3p 和 miR-185-5p 可能作为 LO-FGR 诊断和管理的分子生物标志物;加深对其对成人疾病影响的理解。