Department of Laboratory Medicine, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Zhengzhou Key Laboratory for In Vitro Diagnosis of Hypertensive Disorders of Pregnancy, Zhengzhou, China.
J Cell Mol Med. 2024 Jun;28(12):e18469. doi: 10.1111/jcmm.18469.
The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.
低氧和氧化应激条件下滋养细胞中 DNA 甲基化和转录组的改变对与妊娠相关的疾病有重大影响。然而，确切的机制仍不完全清楚。在这项研究中，我们使用 HTR-8/SVneo 滋养细胞建立了低氧（H 组）和氧化应激（HR 组）模型，并使用简化代表性双硫代测序进行全基因组 DNA 甲基化变化的联合分析，使用 RNA 测序进行转录组表达变化的联合分析。我们的研究结果表明，H 组显示出比 HR 组更多的差异甲基化基因和差异表达基因。在 H 组中，只有 0.90%的所有差异表达基因同时显示 DNA 甲基化和转录组表达的变化。在阈值扩大后，HR 组中这一数字增加到 6.29%。值得注意的是，H 组和 HR 组都在轴突导向和 MAPK 信号通路中表现出 DNA 甲基化和转录组表达的同时改变。在启动子区域中差异甲基化的前 25 个 KEGG 途径中，有 11 个途径在 H 组和 HR 组中共同富集，占 44.00%。在 H 组和 HR 组之间差异甲基化的前 25 个转录组 KEGG 途径中，有 10 个途径一致，占 40.00%。通过整合我们以前关于子痫前期胎盘组织中 DNA 甲基化的数据，我们发现 ANKRD37 和 PFKFB3 基因可能通过缺氧条件下 DNA 甲基化介导的转录组表达，参与子痫前期的发病机制。
