Institute for Systems Biology, Seattle, WA, USA.
Program in Development and Fetal Health, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
J Cell Mol Med. 2019 Oct;23(10):6835-6845. doi: 10.1111/jcmm.14567. Epub 2019 Jul 24.
Preterm birth is attributed to neonatal morbidity as well as cognitive and physiological challenges. We have previously identified significant differences in mRNA expression in whole blood and monocytes, as well as differences in miRNA concentration in blood plasma, extracellular vesicles (EV) and EV-depleted plasma in women undergoing spontaneous preterm labour (sPTL). The goal of this analysis was to identify differences in miRNA expression within whole blood (WB) and peripheral monocytes (PM) from the same population of women undergoing sPTL compared with non-labouring controls matched by gestational age. We performed single-end small RNA sequencing in whole blood and peripheral monocytes from women undergoing sPTL with active contractions (24-34 weeks of gestation, N = 15) matched for gestational age to healthy pregnant non-labouring controls (>37 weeks gestation, N = 30) who later delivered at term as a part of the Ontario Birth Study (Toronto, Ontario CA). We identified significant differences in expression of 16 miRNAs in PMs and nine miRNAs in WB in women undergoing sPTL. In PMs, these miRNAs were predicted targets of 541 genes, including 28 previously associated with sPTL. In WB, miRNAs were predicted to target 303 genes, including nine previously associated with sPTL. These genes were involved in a variety of immune pathways, including interleukin-2 signalling. This study is the first to identify changes in miRNA expression in WB and PMs of women undergoing sPTL. Our results shed light on potential mechanisms by which miRNAs may play a role in mediating systemic inflammatory response in pregnant women that deliver prematurely.
早产与新生儿发病以及认知和生理挑战有关。我们之前已经发现,在自发性早产(sPTL)妇女的全血和单核细胞中的 mRNA 表达以及在血浆、细胞外囊泡(EV)和 EV 耗尽血浆中的 miRNA 浓度方面存在显著差异。本分析的目的是鉴定 sPTL 妇女的全血(WB)和外周单核细胞(PM)中的 miRNA 表达差异,与年龄匹配的非临产对照相比。我们对经历 sPTL 且伴有活跃宫缩的妇女(妊娠 24-34 周,N=15)的全血和外周单核细胞进行了单端小 RNA 测序,这些妇女与健康的非临产对照(妊娠>37 周,N=30)相匹配,这些对照后来在安大略出生研究(多伦多,加拿大安大略省)中足月分娩。我们鉴定出了 16 种在 PM 中表达差异显著的 miRNA 和 9 种在 WB 中表达差异显著的 miRNA。在 PM 中,这些 miRNA 是 541 个基因的预测靶点,其中 28 个基因与 sPTL 先前有关联。在 WB 中,miRNA 被预测靶向 303 个基因,其中 9 个基因与 sPTL 先前有关联。这些基因参与了多种免疫途径,包括白细胞介素-2 信号转导。这是第一项鉴定 sPTL 妇女 WB 和 PM 中 miRNA 表达变化的研究。我们的研究结果揭示了 miRNA 可能在介导早产孕妇全身炎症反应中发挥作用的潜在机制。