3,3'-Dichlorobiphenyl (PCB 11) alters the hepatic expression of cytochrome P450 enzymes in the liver of mouse dams exposed orally during pregnancy and lactation

Abstract

Healthy maternal metabolism is critical during pregnancy and lactation to support fetal development and protect against environmental toxins. Polychlorinated biphenyl 11 (PCB 11), a lower-chlorinated, non-legacy congener, is detected in human serum, including pregnant women and children; however, its impact during these sensitive life stages remains poorly understood. This study presents the first comprehensive hepatic proteome analysis of mouse dams exposed to PCB 11 during pregnancy and lactation. Female C57BL/6 J mice received daily oral doses of PCB 11 (0, 1.0 or 6.0 mg/kg) prior to conception through lactation. At postpartum day 21, brain, liver, and serum samples were analyzed for PCB 11 and its metabolites, and hepatic proteomic changes were assessed. Low detection of PCB 11 and its metabolites was observed in tissues, suggesting rapid clearance. Metabolite screening revealed OH-PCB 11, PCB 11 sulfate, and OH-PCB 11 sulfate metabolites in serum. Global proteomics identified significant alterations in hepatic protein expression, including downregulation of cytochrome P450 enzymes, solute carriers, and enzymes involved in fatty acid and steroid metabolism. Pathway enrichment analyses indicated disruptions in xenobiotic metabolism and endocrine pathways. These findings suggest that PCB 11 exposure during pregnancy and lactation impairs hepatic detoxification and metabolic capacity, potentially compromising maternal and offspring health. This work highlights the need for further investigation into the long-term consequences of PCB 11 exposure during pregnancy and lactation.

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