Comprehensive Reproductive Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
J Matern Fetal Neonatal Med. 2022 Dec;35(25):8728-8734. doi: 10.1080/14767058.2021.2000598. Epub 2021 Nov 14.
Placenta-derived extracellular vesicles and their cargoes, especially microRNAs (EV-miRNAs), may contribute to fetal and placental development. During pregnancy, the levels of several maternal blood EV-miRNAs, including miRNAs of placental origin, vary among individuals and change throughout gestation. However, the effects of these miRNAs on fetal growth and trimester-specificity have not been fully elucidated. The purpose of this study is to test the hypothesis that the serum levels of two extracellular vesicles (EV)-miRNAs (miR-127-3p and miR-26b-5p), which may be involved in fetoplacental regulation, would be significantly associated with fetal growth in a trimester-specific manner.
This is a single-center birth cohort of maternal serum samples obtained at both the second and third trimesters. To minimize the influence of confounding factors, the analysis was limited to singleton vaginal deliveries, resulting in 27 participants being included in this study. EV RNAs were isolated using a membrane affinity method, and the relative expression levels of miR-127-3p and miR-26b-5p were measured using the RT-qPCR method with miR-484 as control. The associations between the two EV-miRNAs and fetal and placental growth were evaluated using a linear regression model and compared between the two trimesters.
EV-miR-127-3p levels tended to correlate inversely with the z-scores of birth weight for gestational age (BWGA) and placental weight for gestational age (PWGA) in the second trimester, but not in the third trimester. EV-miR-26b-5p levels were positively associated with birth weight in the second trimester, but this association was weakened in the third trimester.
Our results suggest a trimester-specific association of circulating miRNA levels with fetal and placental growth. The precise roles of EV-miR-127-3p and EV-miR-26b-5p in fetal and placental development warrant further investigation.
胎盘来源的细胞外囊泡及其 cargo，特别是 microRNAs（EV-miRNAs），可能有助于胎儿和胎盘的发育。在怀孕期间，个体之间几种母体外周血 EV-miRNAs 的水平，包括胎盘来源的 miRNAs，会发生变化并随妊娠而改变。然而，这些 miRNAs 对胎儿生长和妊娠特异性的影响尚未完全阐明。本研究旨在检验假设，即两种可能参与胎-胎盘调节的细胞外囊泡（EV）-miRNAs（miR-127-3p 和 miR-26b-5p）的血清水平，将以妊娠特异性的方式与胎儿生长显著相关。
这是一项单中心的母体外周血样本出生队列研究，在第二和第三个三个月均获得了样本。为了最大限度地减少混杂因素的影响，分析仅限于单胎阴道分娩，因此本研究纳入了 27 名参与者。使用膜亲和力法分离 EV RNA，使用 RT-qPCR 法测量 miR-127-3p 和 miR-26b-5p 的相对表达水平，并以 miR-484 为对照。使用线性回归模型评估这两种 EV-miRNA 与胎儿和胎盘生长之间的关系，并在两个三个月期间进行比较。
EV-miR-127-3p 水平在第二个三个月与胎龄体重 z 评分（BWGA）和胎盘重量与胎龄 z 评分（PWGA）呈负相关趋势，但在第三个三个月没有相关性。EV-miR-26b-5p 水平与第二个三个月的出生体重呈正相关，但在第三个三个月这种相关性减弱。
我们的结果表明循环 miRNA 水平与胎儿和胎盘生长存在妊娠特异性关联。EV-miR-127-3p 和 EV-miR-26b-5p 在胎儿和胎盘发育中的精确作用需要进一步研究。
