摘要
目的 探究正常流产组与不明原因复发性自然流产(URSA)组之间的差异表达基因,寻找URSA诊治的靶向通路、标志物。方法 2023年10月至2024年4月在常德市第一人民医院,收集临床正常妊娠7~10周,且自愿要求终止妊娠者8例、URSA 8例,采集两组蜕膜组织进行转录组测序。通过基因本体(GO)、基因组百科全书分析(KEGG)、基因集富集分析(GSEA)及蛋白质互作网络(PPI)寻找潜在差异标志物,并对标志物及通路进行验证。结果 差异基因表达分析共筛选2503个差异表达基因,其中上调基因1801个,下调基因702个。转录组测序结果证实,磷脂酰肌醇3-激酶/丝氨酸/苏氨酸蛋白激酶B(PI3K/AKT)信号通路在URSA组显著下调。通过RT-PCR、Western blotting、免疫组织荧光染色的方法进一步证实了转录组测序结果。在细胞层面,PI3K/AKT信号通路激动剂可显著提高子宫内膜间质细胞的增殖、迁移、侵袭能力。结论 PI3K/AKT信号通路可能在URSA发生发展中发挥着重要的作用,本研究为URSA的诊治提供了新的诊治靶点。
Objective To explore the differentially expressed genes between the normal miscarriage group and the unexplained recurrent spontaneous abortion(URSA)group,and to identify potential targeted pathways and biomarkers for the diagnosis and treatment of URSA.Methods From October 2023 to April 2024,decidual tissues were collected from 8 cases of clinically normal pregnancies(7-10 weeks)where participants voluntarily requested pregnancy termination,and 8 cases of URSA at the First People's Hospital of Changde City.Transcriptome sequencing was performed on the collected decidual tissues.Potential differential biomarkers were identified through Gene Ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,Gene Set Enrichment Analysis(GSEA),and Protein-Protein Interaction(PPI)network analysis.The biomarkers and pathways were further validated.Results Differential gene expression analysis identified a total of 2503 differentially expressed genes,including 1801 upregulated and 702 downregulated genes.Transcriptome sequencing revealed that the PI3K/AKT signaling pathway was significantly downregulated in the URSA group.This finding was further confirmed by RT-PCR,Western blotting,and immunofluorescence staining.At the cellular level,activation of the PI3K/AKT signaling pathway significantly enhanced the proliferation,migration,and invasion abilities of endometrial stromal cells.Conclusions The PI3K/AKT signaling pathway may play a crucial role in the development and progression of URSA.This study provides new potential targets for the diagnosis and treatment of URSA.
作者
崔竞红
陈杨
张朝霞
CUI Jinghongl;CHEN Yang;ZHANG Chaoxia(Department of Obstetrics,The First People's Hospital of Changde City,Changde,Hunan 415000,China;Health Service Department of the 954th Hospital of the Chinese People's Liberation Army,Shannan,Xizang 856099,China)
出处
《中国优生与遗传杂志》
2025年第3期531-538,共8页
Chinese Journal of Birth Health & Heredity
