Table_3_Integrated Proteotranscriptomics of Human Myometrium in Labor Landscape Reveals the Increased Molecular Associated With Inflammation Under Hypoxia Stress.xlsx

During labor, a variety of coordinated physiological and biochemical events cause the myometrium to transition from a quiescent to contractile state; the molecular mechanisms responsible for this transition, however, remain unclear. To better understand this transition at a molecular level, the global transcriptome and proteome of human myometrial samples in labor and those not in labor were investigated through RNA sequencing (RNA-seq) and quantitative liquid chromatography–tandem mass spectrometry (LC-MS/MS) via data-independent acquisition (DIA) and parallel reaction monitoring (PRM) methods. Furthermore, an integrated proteotranscriptomic analysis was performed to explore biological processes and pathway alterations during labor; this analysis identified 1,626 differentially expressed mRNAs (1,101 upregulated, 525 downregulated) and 135 differentially expressed proteins (97 upregulated, 38 downregulated) in myometrium between nonlabor and in labor groups. The comprehensive results of these analyses showed that the upregulated mRNAs and proteins increased inflammation under hypoxia stress in the myometrium under labor, and related proteins and cytokines were validated by PRM and Luminex assays. Our study confirmed the biological process of inflammation and hypoxia in laboring myometrium at the transcriptome and proteome levels and provided recourse to discover new molecular and biological changes during labor.

分娩过程中，多种协同调控的生理与生化事件可促使子宫肌层（myometrium）从静息状态转换为收缩状态；然而，介导这一转换的分子机制至今仍未明确。为从分子层面更好地阐释该转换过程，本研究针对分娩与未分娩状态的人类子宫肌层样本，分别通过RNA测序（RNA-seq）以及基于数据非依赖采集（DIA）、平行反应监测（PRM）的定量液相色谱-串联质谱（LC-MS/MS）技术，对其全局转录组与蛋白质组展开分析。此外，本研究还开展了蛋白质组-转录组整合分析，以探究分娩过程中的生物学进程与通路变化；该分析在分娩组与未分娩组的子宫肌层样本中，共鉴定出1626个差异表达mRNA（其中1101个上调、525个下调）以及135个差异表达蛋白质（其中97个上调、38个下调）。上述分析的综合结果表明，分娩状态下子宫肌层中上调的mRNA与蛋白质，可加剧缺氧应激下的炎症反应；相关蛋白质与细胞因子亦通过PRM技术及Luminex检测得到了验证。本研究从转录组与蛋白质组层面证实了分娩子宫肌层的炎症与缺氧生物学进程，并为挖掘分娩过程中全新的分子与生物学变化提供了研究依据。