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Significant metabolic alterations in mouse dams exposed to an environmental mixture of polychlorinated biphenyls (PCBs) during gestation and lactation: Insights into PCB and metabolite profiles
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2024-09-19 , DOI: 10.1016/j.etap.2024.104567 Xueshu Li, Youjun P. Suh, Rebecca J. Wilson, Pamela J. Lein, Julia Y. Cui, Hans-Joachim Lehmler
Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2024-09-19 , DOI: 10.1016/j.etap.2024.104567 Xueshu Li, Youjun P. Suh, Rebecca J. Wilson, Pamela J. Lein, Julia Y. Cui, Hans-Joachim Lehmler
Polychlorinated biphenyls (PCBs) and their metabolites are linked to developmental neurotoxicity, but their levels in the gestational and lactational environment remain unexplored. This study investigated the effects of dietary exposure to the Fox River Mixture (FRM) on serum levels of PCBs and their metabolites in female C57BL/6 J mice. Mice were exposed to 0.1, 1.0, or 6.0 mg/kg body weight/day of FRM beginning two weeks before mating and throughout gestation and lactation. Serum samples collected from the dams at weaning were analyzed using gas chromatograph-tandem mass spectrometry and nontarget liquid chromatography-high resolution mass spectrometry. Results showed complex and dose-dependent differences in PCB and metabolite profiles. Untargeted metabolomics revealed alterations in metabolites involved in glucuronidation. Network analysis suggested disturbances in heme and amino acid metabolism associated with higher chlorinated PCBs. These findings suggested that PCBs and metabolites present in the gestational and lactation environment of mice may contribute to developmental neurotoxicity in rodents.
中文翻译:
在妊娠和哺乳期间暴露于多氯联苯 (PCB) 环境混合物的小鼠母细胞的显着代谢改变:深入了解 PCB 和代谢物概况
多氯联苯 (PCB) 及其代谢物与发育神经毒性有关,但它们在妊娠和哺乳环境中的水平仍未得到探索。本研究调查了饮食中 Fox River 混合物 (FRM) 对雌性 C57BL/6 J 小鼠血清 PCBs 及其代谢物水平的影响。小鼠从交配前两周开始以及整个妊娠和哺乳期暴露于 0.1、1.0 或 6.0 mg/kg 体重/天的 FRM。使用气相色谱-串联质谱和非目标液相色谱-高分辨率质谱分析断奶时从母猪收集的血清样品。结果显示 PCB 和代谢物谱存在复杂和剂量依赖性差异。非靶向代谢组学揭示了参与葡萄糖醛酸化的代谢物的改变。网络分析表明,血红素和氨基酸代谢的紊乱与较高的氯化 PCB 有关。这些发现表明,存在于小鼠妊娠和哺乳环境中的 PCB 和代谢物可能导致啮齿动物的发育神经毒性。
更新日期:2024-09-19
中文翻译:
在妊娠和哺乳期间暴露于多氯联苯 (PCB) 环境混合物的小鼠母细胞的显着代谢改变:深入了解 PCB 和代谢物概况
多氯联苯 (PCB) 及其代谢物与发育神经毒性有关,但它们在妊娠和哺乳环境中的水平仍未得到探索。本研究调查了饮食中 Fox River 混合物 (FRM) 对雌性 C57BL/6 J 小鼠血清 PCBs 及其代谢物水平的影响。小鼠从交配前两周开始以及整个妊娠和哺乳期暴露于 0.1、1.0 或 6.0 mg/kg 体重/天的 FRM。使用气相色谱-串联质谱和非目标液相色谱-高分辨率质谱分析断奶时从母猪收集的血清样品。结果显示 PCB 和代谢物谱存在复杂和剂量依赖性差异。非靶向代谢组学揭示了参与葡萄糖醛酸化的代谢物的改变。网络分析表明,血红素和氨基酸代谢的紊乱与较高的氯化 PCB 有关。这些发现表明,存在于小鼠妊娠和哺乳环境中的 PCB 和代谢物可能导致啮齿动物的发育神经毒性。