Trifonova E A, Markov A V, Zarubin A A, Babovskaya A A, Gavrilenko M M, Gabidulina T V, Stepanov V A
Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, 634050 Russia.
Siberian State Medical University, Tomsk, 634050 Russia.
Mol Biol (Mosk). 2025 Mar-Apr;59(2):212-233.
Numerous histological studies have demonstrated that impaired placentation processes are involved in the key pathogenetic mechanisms of great obstetrical syndromes (GOSs). However, the molecular basis of this discovery is still unclear. Therefore, the objectives of this work were to characterize the molecular mechanisms and to search for new genetic markers of pregnancy complications via an integrative analysis of the data obtained by genome-wide expression profiling of placental tissue in preeclampsia, intrauterine growth restriction (IUGR), premature labor (PL), and physiological pregnancy (PP). Oxidative stress, ferroptosis, and disordered intercellular interactions in placenta were assumed to be common pathogenetic mechanisms of GOSs. A total of 64 genes were found to be significantly dysregulated in at least two pregnancy complications. Maternal endothelial cells and syncytiotrophoblast cells were the most significant cell populations enriched in these genes. A computational analysis and the topology of the protein-protein interaction network identified SOD1, ACTG1, TXNRD1, TKT, GCLM, GOT1, ACO1, and UBB as hub genes. A set of key regulators that trigger the reaction cascades involving the differentially expressed genes was found to include MAPK3, MID1, LCMT1, DUSP10, TOPS, SOX10, EGFR, TFAP2A, GLIS1, NR2F1, NR2F2, PAX5, HSF1, and BCL6. The genes were overrepresented in the MAP kinase and interferon-γ response signaling pathways. The above genes and their products were assumed to provide the most promising biomarkers for developing new approaches to risk factor assessment and targeted therapy in GOSs. Further studies should be aimed at clarifying their functional and diagnostic significance in pregnancy complications.
众多组织学研究表明，胎盘形成过程受损参与了重大产科综合征（GOSs）的关键发病机制。然而，这一发现的分子基础仍不清楚。因此，本研究的目的是通过对先兆子痫、宫内生长受限（IUGR）、早产（PL）和生理妊娠（PP）胎盘组织全基因组表达谱数据的综合分析，来表征分子机制并寻找妊娠并发症的新遗传标记。胎盘的氧化应激、铁死亡和细胞间相互作用紊乱被认为是GOSs的常见发病机制。共发现64个基因在至少两种妊娠并发症中显著失调。母体内皮细胞和合体滋养层细胞是这些基因中富集最显著的细胞群体。蛋白质-蛋白质相互作用网络的计算分析和拓扑结构确定SOD1、ACTG1、TXNRD1、TKT、GCLM、GOT1、ACO1和UBB为枢纽基因。发现一组触发涉及差异表达基因反应级联的关键调节因子包括MAPK3、MID1、LCMT1、DUSP10、TOPS、SOX10、EGFR、TFAP2A、GLIS1、NR2F1、NR2F2、PAX5、HSF1和BCL6。这些基因在MAP激酶和干扰素-γ反应信号通路中过度表达。上述基因及其产物被认为是开发GOSs风险因素评估和靶向治疗新方法最有前景的生物标志物。进一步的研究应旨在阐明它们在妊娠并发症中的功能和诊断意义。
