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足月分娩过程中母体外周血转录组变化模拟自发性早产前的干扰。

Transcriptome changes in maternal peripheral blood during term parturition mimic perturbations preceding spontaneous preterm birth†.

出版信息

Biol Reprod. 2022 Jan 13;106(1):185-199. doi: 10.1093/biolre/ioab197.

Abstract

The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess labor-specific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth.

摘要

分娩的复杂生理过程包括临产的开始,这需要协调刺激涉及子宫收缩性、宫颈成熟和羊膜激活的共同途径。然而,除非这些组织中的临产特有的过程可以在非侵入性样本(如外周血)中进行探测,否则它们作为预测性生物标志物的用途有限。在此,我们利用转录组数据集来评估足月分娩妇女外周血中的临产特异性变化。我们确定了一组在临产时表达差异的基因,这些基因富集了免疫过程,这些基因表达变化与之前研究的结果强烈相关,为我们的发现提供了计算机验证。然后,我们发现了母体循环中与足月时羊膜、子宫肌层和宫颈的临产特异性转录组变化相关的显著相关性,表明组织特异性临产特征部分反映在外周血中。最后,我们证明了足月分娩时的外周血转录组变化与无症状妇女在被诊断为早产胎膜早破之前的变化之间存在显著重叠,这些妇女最终早产。总的来说,我们提供的证据表明,足月分娩的正常过程具有独特的免疫表达特征,这可能是评估分娩状态和潜在识别早产风险妇女的有用工具。

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