Journal article
Single-cell transcriptomics showed that maternal PCB exposure dysregulated cell type-specific metabolic responses in the livers of female mouse offsprings
Drug metabolism and disposition, Vol.54(2), 100174
02/2026
DOI: 10.1016/j.dmd.2025.100174
PMID: 41520576
Abstract
Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that bioaccumulate in the food chain and readily cross the placenta, raising concerns for developmental toxicity. While PCB exposure has been associated with metabolic and neurodevelopmental disorders, its cell type-specific effects on liver development remain poorly understood. This study aimed to investigate how maternal exposure to an environmentally relevant Fox River PCB mixture affects liver development in female offspring at single-cell resolution. We hypothesized that developmental PCB exposure disrupts hepatic metabolic and immune function in a cell-type-specific manner. Using single-cell RNA sequencing (scRNA-seq) on liver tissue from postnatal day 28 female mice exposed to PCBs throughout gestation and lactation, we identified major hepatic and immune cell populations and assessed cell-specific transcriptional responses. PCB exposure significantly altered the proportions of endothelial cells and Kupffer cells and reduced neutrophil abundance in the liver. Transcriptomic analysis revealed that PCBs dysregulated key functional pathways in hepatocytes and non-parenchymal cells, including ER stress responses, drug metabolism, and glucose/insulin signaling. Notably, hepatocytes exhibited upregulation of phase-I drug-metabolizing enzymes and uptake transporters, but downregulation of phase-II enzymes and efflux transporters. Kupffer cells and endothelial cells exhibited altered immune and metabolic gene expression, and intercellular communication analysis predicted that PCB exposure disrupted fibronectin, collagen, and chemokine signaling. RT-qPCR validation confirmed increased expression of hepatic ER stress markers. Together, these findings demonstrate that developmental PCB exposure induces persistent, cell-type-specific transcriptomic reprogramming in the liver, impairing metabolic and immune functions. This study highlights the utility of single-cell transcriptomics for revealing toxicant effects with cellular precision during critical windows of development.
Details
- Title: Subtitle
- Single-cell transcriptomics showed that maternal PCB exposure dysregulated cell type-specific metabolic responses in the livers of female mouse offsprings
- Creators
- Joe Jongpyo LimYoujun SuhXueshu LiRebecca J. WilsonHans-Joachim LehmlerPamela J. LeinJulia Yue Cui
- Resource Type
- Journal article
- Publication Details
- Drug metabolism and disposition, Vol.54(2), 100174
- DOI
- 10.1016/j.dmd.2025.100174
- PMID
- 41520576
- NLM abbreviation
- Drug Metab Dispos
- ISSN
- 0090-9556
- eISSN
- 1521-009X
- Publisher
- Elsevier
- Grant note
- National Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health: ES0 05605, ES013661, ES014901, ES030197, ES031098, F31DK139707, UW T32ES007032 EHM-BRACE Center
This work was supported by the National Institute of Environmental Health Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (ES0 05605, ES013661, ES014901, ES030197, ES031098, and F31DK139707) , as well as the UW T32ES007032 and the EHM-BRACE Center.
- Language
- English
- Electronic publication date
- 09/25/2025
- Date published
- 02/2026
- Academic Unit
- Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute; Iowa Superfund Research Program
- Record Identifier
- 9984969239702771
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