Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
Front Immunol. 2023 Aug 15;14:1213902. doi: 10.3389/fimmu.2023.1213902. eCollection 2023.
Term birth (TB) and preterm birth (PTB) are characterized by uterine contractions, rupture of the chorioamniotic membrane, decidual activation, and other physiological and pathological changes. In this study, we hypothesize that inflammation can cause changes in mRNA expression and metabolic stability in the placenta, decidua, chorioamniotic membrane, uterus and peripheral blood, ultimately leading to PTB.
To comprehensively assess the effects of inflammation on mRNA expression and metabolite production in different tissues of pregnancy, we used a mouse PTB model by intraperitoneally injecting lipopolysaccharide (LPS) and integrated transcriptomics and metabolomics studies.
Our analysis identified 152 common differentially expressed genes (DEGs) and 8 common differentially expressed metabolites (DEMs) in the placenta, decidua, chorioamniotic membrane, uterus, and peripheral blood, or placenta and uterus after LPS injection, respectively. Our bioinformatics analysis revealed significant enrichment of the NOD-like receptor signaling pathway (mmu04621), TNF signaling pathway (mmu04668), IL-17 signaling pathway (mmu04657), and NF-kappa B signaling pathway in the transcriptomics of different tissues, and Hormone synthesis, Lysosome, NOD-like receptor signaling pathway, and Protein digest and absorption pathway in metabolomics. Moreover, we found that several upstream regulators and master regulators, including STAT1, STAT3, and NFKB1, were altered after exposure to inflammation in the different tissues. Interaction network analysis of transcriptomics and metabolomics DEGs and DEMs also revealed functional changes in mice intraperitoneally injected with LPS.
Overall, our study identified significant and biologically relevant alterations in the placenta, decidua, chorioamniotic membrane, uterus, peripheral blood transcriptome and the placenta and uterus metabolome in mice exposed to LPS. Thus, a comprehensive analysis of different pregnancy tissues in mice intraperitoneally injected with LPS by combining transcriptomics and metabolomics may help to systematically understand the local and systemic changes associated with PTB caused by inflammation.
足月产（TB）和早产（PTB）的特征是子宫收缩、绒毛膜羊膜破裂、蜕膜激活和其他生理和病理变化。在这项研究中，我们假设炎症会导致胎盘、蜕膜、绒毛膜羊膜、子宫和外周血中 mRNA 表达和代谢稳定性发生变化，最终导致 PTB。
为了全面评估炎症对妊娠不同组织中 mRNA 表达和代谢产物产生的影响，我们使用腹腔注射脂多糖（LPS）的小鼠 PTB 模型，并进行了转录组学和代谢组学研究。
我们的分析分别在 LPS 注射后的胎盘、蜕膜、绒毛膜羊膜、子宫和外周血，或胎盘和子宫中鉴定出 152 个共同差异表达基因（DEGs）和 8 个共同差异表达代谢物（DEMs）。我们的生物信息学分析显示，在不同组织的转录组学中，NOD 样受体信号通路（mmu04621）、TNF 信号通路（mmu04668）、IL-17 信号通路（mmu04657）和 NF-kappa B 信号通路（mmu04657）显著富集，而在代谢组学中则是激素合成、溶酶体、NOD 样受体信号通路和蛋白消化吸收通路。此外，我们发现，几种上游调节剂和主调节剂，包括 STAT1、STAT3 和 NFKB1，在不同组织受到炎症刺激后发生改变。转录组学和代谢组学 DEGs 和 DEMs 的相互作用网络分析也显示了 LPS 注射后小鼠的功能变化。
总的来说，我们的研究在 LPS 暴露的小鼠胎盘、蜕膜、绒毛膜羊膜、子宫、外周血转录组和胎盘及子宫代谢组中发现了显著的、具有生物学意义的改变。因此，通过结合转录组学和代谢组学对 LPS 注射的小鼠不同妊娠组织进行综合分析，可能有助于系统地了解炎症引起的 PTB 相关的局部和全身变化。
