Adverse intrauterine environment has been considered a predisposing factor for fetal programming in preeclampsia. Using human umbilical vein endothelial cells (HUVECs), we specifically explored if aberrant histone methylation occurs in fetal endothelial cells in preeclampsia. Strikingly, we found that increased di‐, and tri‐methylation of histone H3 lysine 9 (H3K9me2 and H3K9me3) expression were associated with upregulation of methyltransferase G9a and downregulation of endothelial nitric oxide synthase and CuZn‐SOD expression in preeclamptic HUVECs. We further demonstrated that hypoxia‐induced hypermethylation of H3K9 and reduced CuZn‐SOD expression mimicked what were seen in preeclamptic HUVECs and inhibition of G9a could attenuate these hypoxia‐induced adverse events. Our study was the first to identify hypermethylation status in fetal endothelial cells in preeclampsia, which provides plausible evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in fetal endothelial cells which may have a significant impact on fetal programming in preeclampsia.

中文翻译：

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来自先兆子痫妊娠的胎儿内皮细胞中组蛋白 H3K9 甲基化的上调。

不良的宫内环境被认为是先兆子痫胎儿编程的诱发因素。使用人脐静脉内皮细胞 (HUVEC)，我们专门探讨了先兆子痫的胎儿内皮细胞中是否发生异常组蛋白甲基化。引人注目的是，我们发现组蛋白 H3 赖氨酸 9（H3K9me2 和 H3K9me3）表达的二甲基化和三甲基化增加与先兆子痫 HUVEC 中甲基转移酶 G9a 的上调和内皮一氧化氮合酶和 CuZn-SOD 表达的下调有关。我们进一步证明，缺氧诱导的 H3K9 高甲基化和降低的 CuZn-SOD 表达类似于先兆子痫 HUVEC 中所见，抑制 G9a 可以减轻这些缺氧诱导的不良事件。