Zhou Ping, Mo Dan, Huang Hanji, Xu Jiaqi, Liao Baoying, Wang Yinxue, Mao Di, Zeng Zhonghong, Huang Ziying, Zhang Chao, Yang Yihua, Yu Yang, Pan Heng, Li Rong
State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, China.
Life Med. 2024 Oct 21;3(5):lnae036. doi: 10.1093/lifemedi/lnae036. eCollection 2024 Oct.
Recurrent implantation failure (RIF) is a leading impediment to assisted reproductive technology, yet the underlying pathogenesis of RIF remains elusive. Recent studies have sought to uncover novel biomarkers and etiological factors of RIF by profiling transcriptomes of endometrial samples. Nonetheless, the inherent heterogeneity among published studies and a scarcity of experimental validations hinder the identification of robust markers of RIF. Hence, we integrated six publicly accessible datasets with 209 samples, including microarray profiles of endometrial samples in the secretory phase. After removing batch effects, we identified 175 differentially expressed genes. Gene set enrichment analysis identified dysregulation of immunological pathways in RIF. We also observed altered immune infiltration and pro-inflammatory cytokines in RIF. Protein-protein interaction network analysis identified ten hub genes, representing two co-expression modules significantly related to RIF. Knockdown of , one of the hub genes, promoted the epithelial-mesenchymal transition process and resulted in elevated levels of pro-inflammatory cytokines. Collectively, our study reveals abnormal gene expressions involving the regulation of epithelial-mesenchymal transition and immune status in RIF, providing valuable insights into its pathogenesis.
反复种植失败（RIF）是辅助生殖技术的主要障碍，然而RIF的潜在发病机制仍不清楚。最近的研究试图通过分析子宫内膜样本的转录组来揭示RIF的新生物标志物和病因。尽管如此，已发表研究之间固有的异质性以及实验验证的缺乏阻碍了RIF可靠标志物的鉴定。因此，我们整合了六个可公开获取的数据集，包含209个样本，其中包括分泌期子宫内膜样本的微阵列图谱。去除批次效应后，我们鉴定出175个差异表达基因。基因集富集分析确定了RIF中免疫途径的失调。我们还观察到RIF中免疫浸润和促炎细胞因子的改变。蛋白质-蛋白质相互作用网络分析确定了十个枢纽基因，代表两个与RIF显著相关的共表达模块。敲低其中一个枢纽基因可促进上皮-间质转化过程，并导致促炎细胞因子水平升高。总的来说，我们的研究揭示了RIF中涉及上皮-间质转化调控和免疫状态的异常基因表达，为其发病机制提供了有价值的见解。
