草甘膦除草剂（GBHs）或其活性成分草甘膦（Gly）会导致大鼠着床失败。我们的目的是阐明这些化合物的作用机制，评估接受标记白血病抑制因子 (Lif) 基因的转录和表观遗传状态。 F0 大鼠从妊娠第 9 天直至断奶，分别以 3.8 或 3.9mg Gly/kg/天口服暴露于 GBH 或 Gly。 F1 雌性在 GD5 时交配并收集子宫样本。通过计算机预测 Lif 基因调控区域中的甲基化敏感限制性酶 (MSRE) 位点和转录因子。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 降低了 Lif mRNA 水平并导致 DNA 高甲基化。 GBH 增加 H3Ac 水平，而 Gly 降低 H3Ac 水平；两种化合物均增强 H3K27me3 水平。最后，GBH 和 Gly 都在 Lif 的调控区域中诱导了类似的表观遗传改变。版权所有 © 2024。由 Elsevier B.V. 出版。

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 3.9mg 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.Copyright © 2024. Published by Elsevier B.V.