Liggins Institute, University of Auckland, Auckland 1142, New Zealand.
Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide 5001, Australia.
Int J Mol Sci. 2024 Sep 2;25(17):9536. doi: 10.3390/ijms25179536.
Globally, preterm birth (PTB) is a primary cause of mortality and morbidity in infants, with PTB rates increasing worldwide over the last two decades. Biomarkers for accurate early prediction of PTB before the clinical event do not currently exist. Given their roles in the development and progression of many disease states, there has been increasing interest in the utility of microRNAs (miRNAs) as early biomarkers for pregnancy-related disorders, including PTB. The present study was designed to examine potential differences in miRNA abundances in maternal plasma from mothers with infants born following a moderate to late (28-36 weeks' gestation, n = 54) spontaneous PTB (SPTB) compared to mothers with matched term infants (n = 54). Maternal plasma collected at 15 weeks' gestation were utilised from the Auckland and Adelaide cohorts from the Screening for Pregnancy Endpoints (SCOPE) study. miRNAs in plasma were quantified using the NanoString nCounter expression panel (800 miRNAs). The top four most abundant miRNAs were significantly decreased in the plasma of mothers in the SPTB group with results consistent across both cohorts and pathway analysis was undertaken to examine the biological processes linked to the dysregulated miRNAs. The top candidate miRNAs (miRs-451a, -223-3p, let-7a-5p, and -126-3p) were linked to gene pathways associated with inflammation, apoptosis, and mitochondrial biogenesis. Moreover, miRNAs were consistently less abundant in the plasma of mothers of preterm infants across both sites, suggesting potential global dysregulation in miRNA biogenesis. This was supported by a significant downregulation in expression of key genes that are involved in miRNA biogenesis (, , and ) across both sites in the SPTB group. In summary, the present study has identified miRNAs in maternal plasma that may provide predictive utility as early biomarkers for the risk of later SPTB. Importantly, these observations were conserved across two independent cohorts. Further, our data provide evidence for a persistent decrease in miRNA abundance in mothers who later experienced an SPTB, which is likely to have widespread consequences for gene regulation and epigenetic processes.
全球范围内，早产（PTB）是婴儿死亡和发病的主要原因，在过去的二十年中，全球范围内的 PTB 发生率一直在上升。目前尚无在临床事件发生前准确预测 PTB 的生物标志物。鉴于它们在许多疾病状态的发展和进展中的作用，人们越来越关注 microRNAs（miRNAs）作为包括 PTB 在内的妊娠相关疾病的早期生物标志物的效用。本研究旨在检查来自中度至晚期（28-36 孕周）自发性早产（SPTB）婴儿母亲的母体血浆中 miRNA 丰度的潜在差异与具有匹配足月婴儿的母亲（n=54）相比。使用来自奥克兰和阿德莱德队列的 Screening for Pregnancy Endpoints（SCOPE）研究中的 15 周妊娠采集的母体血浆。使用 NanoString nCounter 表达谱（800 个 miRNA）定量血浆中的 miRNA。SPTB 组中母亲血浆中前四种最丰富的 miRNA 显著减少，结果在两个队列中均一致，并且进行了途径分析以检查与失调 miRNA 相关的生物学过程。顶级候选 miRNA（miR-451a、-223-3p、let-7a-5p 和 -126-3p）与与炎症、细胞凋亡和线粒体生物发生相关的基因途径相关。此外，在两个地点的早产儿母亲的血浆中，miRNA 始终较少，这表明 miRNA 生物发生存在潜在的全球失调。这得到了 SPTB 组中两个地点关键基因表达下调的支持，这些基因涉及 miRNA 生物发生（ 、 和 ）。总之，本研究确定了母体血浆中的 miRNA，这些 miRNA 可能作为 SPTB 后期风险的预测性生物标志物提供效用。重要的是，这些观察结果在两个独立的队列中都得到了保留。此外，我们的数据提供了证据表明，后来经历 SPTB 的母亲的 miRNA 丰度持续下降，这可能对基因调控和表观遗传过程产生广泛影响。
