Journal article
The Bladder as a Target for PCB Toxicity: Evidence from PCB Levels, Phase I Metabolite Levels, and Cytochrome P450 Expression Following Developmental Exposure to a Human-Relevant PCB Mixture in Mice
Chemical research in toxicology, Vol.39(2), pp.236-247
01/22/2026
DOI: 10.1021/acs.chemrestox.5c00431
PMID: 41568709
Appears in UI Libraries Support Open Access
Abstract
Lower urinary tract dysfunction is multifactorial, yet the role of environmental exposure remains poorly investigated. Developmental exposure to polychlorinated biphenyls (PCBs) has been linked to altered voiding in mice; however, the disposition of PCBs in the bladder, their bioactivation, and their effects on cytochrome P450 (CYP) expression remain unclear. We exposed mice to an environmentally relevant PCB mixture via maternal diet during gestation and lactation (vehicle, 0.1, 1, or 6 mg/kg/day). Offspring were euthanized at 6 to 7 weeks of age. PCB and hydroxylated PCB (OH-PCB) levels were quantified in the bladder, liver, blood, and urine. CYP expression was measured in the bladder and liver. PCBs and OH-PCBs accumulated in all tissues in dose- and sex-dependent manners, with higher-chlorinated congeners (e.g., PCB118, PCB138, PCB153, and PCB180) preferentially retained. Females exhibited greater hepatic accumulation, reduced urinary elimination, and distinct CYP regulation characterized by increased hepatic and decreased bladder expression. These findings, for the first time, define the signature of PCBs and OH-PCBs in the bladder and reveal a sex-specific PCB disposition and CYP responses. Our results provide new mechanistic insights into developmental PCB exposure and its potential contribution to voiding dysfunction in wildlife, domestic animals, and humans.
Details
- Title: Subtitle
- The Bladder as a Target for PCB Toxicity: Evidence from PCB Levels, Phase I Metabolite Levels, and Cytochrome P450 Expression Following Developmental Exposure to a Human-Relevant PCB Mixture in Mice
- Creators
- Hui Wang - University of IowaElaine A Schumacher - University of Wisconsin–MadisonAudrey Spiegelhoff - University of Wisconsin–MadisonConner L Kennedy - University of Wisconsin–MadisonMonica M Ridlon - University of Wisconsin–MadisonRachel F Marek - University of IowaKimberly P Keil Stietz - University of Wisconsin–MadisonHans-Joachim Lehmler - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Chemical research in toxicology, Vol.39(2), pp.236-247
- DOI
- 10.1021/acs.chemrestox.5c00431
- PMID
- 41568709
- NLM abbreviation
- Chem Res Toxicol
- ISSN
- 1520-5010
- eISSN
- 1520-5010
- Publisher
- American Chemical Society
- Grant note
- National Institute of Environmental Health Sciences: F31 ES036876
The authors gratefully acknowledge Dr. Keri C. Hornbuckle from the Analytical Core of the Iowa Superfund Research Program for the support with GC-MS/MS analyses. We also thank Brian Westra for his assistance with data management.
- Language
- English
- Date published
- 01/22/2026
- Academic Unit
- Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute; IIHR--Hydroscience and Engineering
- Record Identifier
- 9985130240102771
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