Ling Ling, Xu Guiqin, Fang Miao, Chen Jianquan, Gong Ming, Wang TianMing, Ju Rong, Nie Sipei
Department of Gynecology and Obstetrics, Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, Jiangsu, China.
Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, China.
J Proteomics. 2025 Mar 20;313:105383. doi: 10.1016/j.jprot.2025.105383. Epub 2025 Jan 8.
COVID-19 still spreads worldwide, and repeated infections are hard to avoid. Maternal infection during pregnancy is associated with adverse maternal and neonatal outcomes. Our study used a multi-omics profiling method to explore the proteome and metabolome alteration in early embryonic development after COVID-19 infection. A total of 30 chorionic tissues after artificial abortion (15 infection and 15 no-infection samples) were collected, and the UHPLC-MS/MS and LC-MS/MS were applied in the present study. As a result, 311 significantly differentially expressed proteins were identified. The function annotations revealed that the thermogenesis pathway is the most significantly enriched signaling pathway; PRKAG2, IGF1R, and RPS6KB2 were identified as the hub proteins. There were 359 metabolites significantly altered after infection. The functional annotations revealed that amino acid metabolism was significantly affected, especially beta-alanine metabolism, glutamate metabolism, and histidine metabolism pathways. The metabolites in ovarian steroidogenesis showed a down-regulating trend in the infection group. Finally, we combined the results of proteins and metabolomics analysis. The biosynthesis of the cofactors pathway was identified as significantly enriched in both proteomics and metabolomics datasets. Our findings provide a network of protein regulation and metabolite perturbation during early embryonic development with COVID-19 infection. Our findings can provide valuable insights for further exploration of the complex mechanism of COVID-19-associated pregnancy complications and outcomes. SIGNIFICANCE: COVID-19 has developed into the most prominent and deadliest pandemic respiratory disease in the world, and repeated infections are complicated to avoid. COVID-19 infection during pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preterm birth and stillbirth. However, previous studies mainly focused on its effect on pregnant women, such as the clinical characteristics and gestation outcomes. There is no relevant report about the effects of virus infection on embryos in early pregnancy. The effects of COVID-19 infection changes of the proteins and metabolites during early embryonic development are undefined. Our findings provide an association between protein regulation, metabolite perturbation, and COVID-19 infection, which can provide valuable insights for further exploration of the complex mechanism COVID-19 COVID-19-associated pregnancy complications and adverse pregnancy outcomes.
新冠病毒仍在全球传播，重复感染难以避免。孕期母体感染与不良的母婴结局相关。我们的研究采用多组学分析方法，以探究新冠病毒感染后早期胚胎发育过程中的蛋白质组和代谢组变化。本研究共收集了30份人工流产后的绒毛组织（15份感染样本和15份未感染样本），并应用了超高效液相色谱-串联质谱法（UHPLC-MS/MS）和液相色谱-串联质谱法（LC-MS/MS）。结果，共鉴定出311种显著差异表达的蛋白质。功能注释显示，产热途径是最显著富集的信号通路；已确定PRKAG2、IGF1R和RPS6KB2为核心蛋白。感染后有359种代谢物发生了显著变化。功能注释显示，氨基酸代谢受到显著影响，尤其是β-丙氨酸代谢、谷氨酸代谢和组氨酸代谢途径。感染组中卵巢类固醇生成的代谢物呈下调趋势。最后，我们综合了蛋白质组和代谢组学分析结果。辅因子生物合成途径在蛋白质组学和代谢组学数据集中均被确定为显著富集。我们的研究结果揭示了新冠病毒感染期间早期胚胎发育过程中的蛋白质调控和代谢物扰动网络。我们的研究结果可为进一步探究新冠病毒相关妊娠并发症及结局的复杂机制提供有价值的见解。意义：新冠病毒已发展成为全球最突出、最致命的大流行性呼吸道疾病，重复感染难以避免。孕期感染新冠病毒会增加不良母婴结局的风险，如早产和死产。然而，以往研究主要关注其对孕妇的影响，如临床特征和妊娠结局。尚无关于病毒感染对早孕胚胎影响的相关报道。新冠病毒感染对早期胚胎发育过程中蛋白质和代谢物变化的影响尚不明确。我们的研究结果揭示了蛋白质调控、代谢物扰动与新冠病毒感染之间的关联，可为进一步探究新冠病毒相关妊娠并发症及不良妊娠结局的复杂机制提供有价值的见解。
