Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA 52242, USA.
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA.
Environ Toxicol Pharmacol. 2024 Oct;111:104567. doi: 10.1016/j.etap.2024.104567. Epub 2024 Sep 19.
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.
多氯联苯 (PCBs) 及其代谢物与发育神经毒性有关，但它们在妊娠和哺乳期环境中的水平仍未得到探索。本研究调查了饮食暴露于 Fox River 混合物 (FRM) 对雌性 C57BL/6J 小鼠血清中 PCBs 及其代谢物水平的影响。从交配前两周开始，将小鼠暴露于 0.1、1.0 或 6.0mg/kg 体重/天的 FRM 中，直至妊娠期和哺乳期结束。从断奶时的母鼠采集血清样本，使用气相色谱-串联质谱法和非靶向液相色谱-高分辨率质谱法进行分析。结果显示，PCBs 和代谢物谱呈现复杂且剂量依赖的差异。非靶向代谢组学揭示了与葡萄糖醛酸化相关的代谢物的改变。网络分析表明，与高氯化 PCBs 相关的血红素和氨基酸代谢紊乱。这些发现表明，在妊娠和哺乳期环境中存在的 PCBs 和代谢物可能导致啮齿动物的发育神经毒性。
