Epigenetic alteration of uterine Leukemia Inhibitory Factor gene after glyphosate or a glyphosate-based herbicide exposure in rats

IF 4.2 3区环境科学与生态学 Q2 ENVIRONMENTAL SCIENCES

Environmental toxicology and pharmacology Pub Date : 2024-09-12 DOI:10.1016/j.etap.2024.104564

Ailín Almirón , Virginia Lorenz , Florencia Doná , Jorgelina Varayoud , María Mercedes Milesi

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引用次数: 0

Abstract

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.

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大鼠接触草甘膦或草甘膦类除草剂后子宫白血病抑制因子基因的表观遗传学改变

草甘膦类除草剂（GBHs）或其活性成分草甘膦（Gly）会导致大鼠植入失败。我们的目的是通过评估受孕标志物白血病抑制因子（Lif）基因的转录和表观遗传状态来阐明这些化合物的作用机制。从妊娠日（GD）9开始，F0大鼠口服GBH或Gly，剂量分别为3.8或3.9毫克Gly/公斤/天，直至断奶。F1 雌鼠交配并在 GD5 时采集子宫样本。对 Lif 基因调控区的甲基化敏感限制酶（MSRE）位点和转录因子进行了硅预测。对DNA甲基化状态和组蛋白修饰（组蛋白3和4乙酰化（H3Ac和H4Ac）以及H3赖氨酸-27-三甲基化（H3K27me3））进行了评估。GBH 和 Gly 会降低 Lif mRNA 水平并导致 DNA 超甲基化。GBH 提高了 H3Ac 水平，而 Gly 则降低了 H3Ac 水平；两种化合物都提高了 H3K27me3 水平。最后，GBH 和 Gly 在 Lif 的调控区域诱导了类似的表观遗传学改变。

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来源期刊

Environmental toxicology and pharmacology 医学-毒理学

CiteScore

7.00

自引率

4.70%

发文量

185

审稿时长

34 days

期刊介绍： Environmental Toxicology and Pharmacology publishes the results of studies concerning toxic and pharmacological effects of (human and veterinary) drugs and of environmental contaminants in animals and man. Areas of special interest are: molecular mechanisms of toxicity, biotransformation and toxicokinetics (including toxicokinetic modelling), molecular, biochemical and physiological mechanisms explaining differences in sensitivity between species and individuals, the characterisation of pathophysiological models and mechanisms involved in the development of effects and the identification of biological markers that can be used to study exposure and effects in man and animals. In addition to full length papers, short communications, full-length reviews and mini-reviews, Environmental Toxicology and Pharmacology will publish in depth assessments of special problem areas. The latter publications may exceed the length of a full length paper three to fourfold. A basic requirement is that the assessments are made under the auspices of international groups of leading experts in the fields concerned. The information examined may either consist of data that were already published, or of new data that were obtained within the framework of collaborative research programmes. Provision is also made for the acceptance of minireviews on (classes of) compounds, toxicities or mechanisms, debating recent advances in rapidly developing fields that fall within the scope of the journal.