Glyphosate-based herbicides (GBHs) or its active ingredient, glyphosate (Gly), induce implantation failure in rats. We aimed to elucidate a mechanism of action of these compounds assessing the transcriptional and epigenetic status of the receptivity marker, leukemia inhibitory factor (Lif) gene. F0 rats were orally exposed to GBH or Gly at 3.8 or 3.9 mg Gly/kg/day, respectively, from gestational day (GD) 9 until weaning. F1 females were mated and uterine samples collected at GD5. Methylation-sensitive restriction enzymes (MSRE) sites and transcription factors were in silico predicted in regulatory regions of Lif gene. DNA methylation status and histone modifications (histone 3 and 4 acetylation (H3Ac and H4Ac) and H3 lysine-27-trimethylation (H3K27me3)) were assessed. GBH and Gly decreased Lif mRNA levels and caused DNA hypermethylation. GBH increased H3Ac levels, whereas Gly reduced them; both compounds enhanced H3K27me3 levels. Finally, both GBH and Gly induced similar epigenetic alterations in the regulatory regions of Lif.

中文翻译：

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大鼠草甘膦或基于草甘膦的除草剂暴露后子宫白血病抑制因子基因的表观遗传改变


基于草甘膦的除草剂 （GBH） 或其活性成分草甘膦 （Gly） 诱导大鼠着床失败。我们旨在阐明这些化合物的作用机制，评估容受性标志物白血病抑制因子 （Lif） 基因的转录和表观遗传状态。F0 大鼠从妊娠第 9 天 （GD） 到断奶，分别以 3.8 或 3.9 mg Gly/kg/d 经口暴露于 GBH 或 Gly。F1 雌配并在 GD5 收集子宫样本。甲基化敏感限制酶 （MSRE） 位点和转录因子在 Lif 基因的调控区进行计算机预测。评估 DNA 甲基化状态和组蛋白修饰 （组蛋白 3 和 4 乙酰化 （H3Ac 和 H4Ac） 和 H3 赖氨酸-27-三甲基化 （H3K27me3））。GBH 和 Gly 降低 Lif mRNA 水平并导致 DNA 高甲基化。GBH 增加了 H3Ac 水平，而 Gly 降低了它们;两种化合物都增强了 H3K27me3 水平。最后，GBH 和 Gly 都在 Lif 的调控区诱导了类似的表观遗传改变。