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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
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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

Xueshu Li, Youjun Suh, Rebecca Wilson, Pamela J. Lein, Julia Y. Cui and Hans-Joachim Lehmler
Environmental toxicology and pharmacology, Vol.111, p.104567
10/2024
DOI: 10.1016/j.etap.2024.104567
url
https://escholarship.org/content/qt5rg3n9h3/qt5rg3n9h3.pdfView
Open Access

Abstract

Polychlorinated biphenyls (PCBs) and 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/6J mice. Mice were exposed to 0.1, 1.0, or 6.0mg/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-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. [Display omitted] •PCBs and metabolites were measured in serum from dams exposed to a PCB mixture•PCB but not OH-PCB serum profiles changed with the PCB dose•Serum contained complex sulfated and methylated PCB metabolite mixtures•PCB exposure altered serum levels of metabolites in the glucuronidation pathway•Higher chlorinated PCBs affected heme and amino acid metabolic pathways
Metabolites Exposure Pathway PCB metabolism Polychlorinated biphenyls Untargeted metabolomics

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