Owing to the excessive use of glyphosate-based herbicides (GBHs), the amount of drug residues in corn and alfalfa silage exceeds the standard, which may affect the mammary health of dairy animals. The role of glufosinate-ammonium (GLA) in mammary development is not fully understood. Therefore, the aim of this study was to investigate mammary lesions caused by exposure to GLA in vitro and in vivo. Based on the GLA exposure limit defined, a pregnant mouse exposure model was established to explore the damage caused by GLA exposure in the mammary gland, and a protective mechanism mediated by tea polyphenols (TP) was proposed. Our study shows that perinatal GLA exposure induces inflammation and oxidative stress in the mammary gland. The expression of oxidoreductase complex and mitochondrial protein complex was down-regulated in H-GLA group, suggesting that GLA may affect mitochondrial function. The combined transcriptome and proteomics analysis of mammary gland showed that the differentially expressed genes were enriched in biological regulation and ion transport related biological processes. The key differential gene ER protein retention receptor 1 (KDELR1) suggested that GLA may affect the function of endoplasmic reticulum. In vitro experiments have confirmed that it can activate mitophagy and ERS, and then lead to the up-regulation of apoptosis proteins such as Caspase 3, leading to cell apoptosis, thereby causing breast tissue damage. The strong antioxidant properties of TP can alleviate cell damage by restoring cellular oxidative balance, reducing intracellular ROS content and reducing the expression of inflammatory factors. At the same time, TP could restore the expression of autophagy proteins LC3 and P62, and reduce mitophagy. At the same time, TP can reduce the activation of PERK/eIF2α/CHOP pathway induced by GLA exposure and alleviate ERS, thereby reducing cell apoptosis. These findings shed light on the mechanism of GLA-induced mammary gland damage, improved our understanding of the risk of GLA exposure in domestic animals during pregnancy, and suggested that TP may have potential protective effects against GLA poisoning.

中文翻译：

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茶多酚通过减少内质网应激和自噬来减轻草铵膦诱导的乳腺损伤

由于草甘膦类除草剂 （GBHs） 的过度使用，玉米和苜蓿青贮饲料中的药物残留量超标，这可能会影响奶牛的乳房健康。草铵膦 （GLA） 在乳腺发育中的作用尚不完全清楚。因此，本研究的目的是研究体外和体内暴露于 GLA 引起的乳腺病变。基于定义的 GLA 暴露限值，建立妊娠小鼠暴露模型，探讨 GLA 暴露对乳腺造成的损害，并提出茶多酚 （TP） 介导的保护机制。我们的研究表明，围产期 GLA 暴露会诱发乳腺炎症和氧化应激。H-GLA 组氧化还原酶复合物和线粒体蛋白复合物的表达下调，提示 GLA 可能影响线粒体功能。乳腺的转录组学和蛋白质组学联合分析表明，差异表达基因在生物调控和离子转运相关的生物过程中富集。关键差异基因 ER 蛋白保留受体 1 （KDELR1） 表明 GLA 可能影响内质网的功能。体外实验证实，它可以激活线粒体自噬和 ERS，进而导致 Caspase 3 等凋亡蛋白的上调，导致细胞凋亡，从而引起乳腺组织损伤。TP 具有很强的抗氧化特性，可以通过恢复细胞氧化平衡、降低细胞内 ROS 含量和减少炎症因子的表达来减轻细胞损伤。同时，TP 可以恢复自噬蛋白 LC3 和 P62 的表达，减少线粒体自噬。 同时，TP 可以减少 GLA 暴露诱导的 PERK/eIF2α/CHOP 通路的激活并减轻 ERS，从而减少细胞凋亡。这些发现阐明了 GLA 诱导的乳腺损伤机制，提高了我们对怀孕期间家畜暴露 GLA 风险的理解，并表明 TP 可能对 GLA 中毒具有潜在的保护作用。