Developmental exposure to a human-relevant PCB mixture: impacts on PCB congeners, metabolites, and drug-metabolizing enzymes in the bladder of post-weaning mice

Hui Wang; Alex Goskowicz; Audrey Spiegelhoff; Conner L Kennedy; Monica M Ridlon; Rachel F Marek; Hans-Joachim Lehmler; Kimberly P Keil Stietz

doi:10.1007/s00204-026-04498-6

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Developmental exposure to a human-relevant PCB mixture: impacts on PCB congeners, metabolites, and drug-metabolizing enzymes in the bladder of post-weaning mice

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Developmental exposure to a human-relevant PCB mixture: impacts on PCB congeners, metabolites, and drug-metabolizing enzymes in the bladder of post-weaning mice

Hui Wang, Alex Goskowicz, Audrey Spiegelhoff, Conner L Kennedy, Monica M Ridlon, Rachel F Marek, Hans-Joachim Lehmler and Kimberly P Keil Stietz

Archives of toxicology

07/04/2026

DOI: 10.1007/s00204-026-04498-6

PMID: 42400643

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Abstract

Many women suffer from symptoms associated with dysfunction of the lower urinary tract, including incontinence and overactive bladder, especially during pregnancy. While causes are likely multifactorial, environmental factors, such as exposure to polychlorinated biphenyls (PCBs), have been shown to alter voiding in adult female mice. However, the distribution of PCBs and their metabolites to the bladder and urine, as well as their effects on bladder drug-metabolizing enzyme expression after dosing with PCB mixtures, remains largely unexplored. Female C57BL/6J mice were exposed to MARBLES PCB mixture (0, 0.1, 1, and 6 mg/kg/d) through gestation and lactation, and post-weaning bladder, urine, blood, adipose, and liver were collected for measurement of PCBs and OH-PCBs, and for abundance of cytochrome P450 (Cyp) transcripts in liver and bladder. PCBs and OH-PCBs were detected in all tissues in a dose-dependent manner. Bladder, adipose, and liver retained parent PCBs while OH-PCBs were predominant in urine and blood. Cyp1a2 mRNA abundance was elevated in the liver of the high dose PCB group versus the vehicle, and the same trend was observed in the bladder. These results define the signatures of PCBs and OH-PCBs in the bladders and urine of post-weaning dams exposed to the MARBLES mixture of PCBs and provide a reference for comparison with accumulation in more commonly studied tissues. Our results also provide new insights into the regulation of Cyp1a2 in the liver and bladder, changes that may play a role in how environmental exposures in adulthood alter voiding function.

Pregnancy

Bladder function

OH-PCB

Lower urinary tract symptoms

Cytochrome P450

Phase I metabolism

Details

Title: Subtitle: Developmental exposure to a human-relevant PCB mixture: impacts on PCB congeners, metabolites, and drug-metabolizing enzymes in the bladder of post-weaning mice
Creators: Hui Wang - University of Iowa
Alex Goskowicz - University of Wisconsin–Madison
Audrey Spiegelhoff - University of Wisconsin–Madison
Conner L Kennedy - University of Wisconsin–Madison
Monica M Ridlon - University of Wisconsin–Madison
Rachel F Marek - University of Iowa
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, The University of Iowa, Iowa City, IA, 52246, USA. hans-joachim-lehmler@uiowa.edu
Kimberly P Keil Stietz - University of Wisconsin–Madison
Resource Type: Journal article
Publication Details: Archives of toxicology
DOI: 10.1007/s00204-026-04498-6
PMID: 42400643
ISSN: 0340-5761
eISSN: 1432-0738
Publisher: Springer Nature
Grant note: ES005605 / NIEHS NIH HHS ES035020 / NIEHS NIH HHS ES036876 / NIEHS NIH HHS ES007015 / NIEHS NIH HHS
Language: English
Electronic publication date: 07/04/2026
Academic Unit: Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute; IIHR--Hydroscience and Engineering
Record Identifier: 9985180878302771

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