table1_The Role of Formyl Peptide Receptor 1 in Uterine Contraction During Parturition.xlsx

Parturition involves the transformation of the quiescent myometrium into a highly excitable and contractile state, a process that is driven by changes in myometrial gene expression. This study aimed to identify myometrial transcriptomic signatures and potential novel hub genes in parturition, which have great significance for understanding the underlying mechanisms of successful parturition and treating labor-associated pathologies such as preterm birth. In our study, comparative transcriptome analysis was carried out on human myometrial tissues collected from women undergoing caesarean section at term in the presence (TL = 8) and absence of labor (TNL = 8). A total of 582 differentially expressed genes (DEGs) between TL and TNL tissues were identified. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) revealed that the DEGs were enriched in signal transduction, regulation of signaling receptor activity, inflammatory response, cytokine-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, among others. Thus, transcriptome analysis of the myometrium during term labor revealed that labor onset was associated with an inflammatory response. Moreover, protein-protein interactions network analysis identified FPR1, CXCL8, CXCL1, BDKRB2, BDKRB1, and CXCL2 as the hub genes associated with onset of labor. Formyl peptide receptor 1 (FPR1) was highly expressed in laboring myometrial tissues, with the activation of FPR1 in vitro experiments resulting in increased myometrial contraction. Our findings demonstrate the novel role of FPR1 as a modulator of myometrial contraction.

分娩过程是将静止状态的子宫肌层转化为高度兴奋且具备收缩能力的状态，这一过程由子宫肌层基因表达的变化所驱动。本研究旨在筛选分娩过程中子宫肌层的转录组特征及潜在新型核心基因，这对于阐明成功分娩的潜在机制、治疗早产等分娩相关病理具有重要意义。本研究对足月妊娠行剖宫产术的产妇采集的子宫肌层组织进行了比较转录组分析，分组为分娩组（TL，n=8）与未分娩组（TNL，n=8）。最终在两组组织间共筛选得到582个差异表达基因（differentially expressed genes, DEGs）。基因本体论（Gene Ontology, GO）、京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）及基因集富集分析（Gene Set Enrichment Analysis, GSEA）结果显示，DEGs显著富集于信号转导、信号受体活性调控、炎症反应、细胞因子-细胞因子受体相互作用、IL-17信号通路及TNF信号通路等生物学过程与通路中。综上，足月分娩时子宫肌层的转录组分析结果表明，分娩启动与炎症反应密切相关。此外，蛋白质相互作用网络分析筛选得到FPR1、CXCL8、CXCL1、BDKRB2、BDKRB1及CXCL2这6个与分娩启动相关的核心基因。甲酰肽受体1（Formyl peptide receptor 1, FPR1）在分娩组子宫肌层组织中高表达，体外实验证实FPR1激活可增强子宫肌层收缩能力。本研究结果揭示了FPR1作为子宫肌层收缩调节因子的全新作用。