Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

Nicole M. Breese; Lisa Truong; Xueshu Li; Robyn L. Tanguay; Hans-Joachim Lehmler

doi:10.3390/toxics14050444

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Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

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Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish

Nicole M. Breese, Lisa Truong, Xueshu Li, Robyn L. Tanguay and Hans-Joachim Lehmler

Toxics (Basel), Vol.14(5), 444

05/19/2026

DOI: 10.3390/toxics14050444

PMCID: PMC13211715

PMID: 42198570

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Abstract

Polychlorinated biphenyls (PCBs) persist in the environment as complex mixtures and undergo extensive biotransformation, yet the developmental toxicity of PCB metabolites remains poorly defined. We evaluated developmental, neurobehavioral, and molecular effects of parent PCBs, hydroxylated, methoxylated, and sulfated metabolites, and environmentally relevant mixtures using embryonic zebrafish. This study employed a high-throughput screening approach using nominal exposure concentrations to enable rapid hazard identification and prioritization across a large chemical series. Morphological abnormalities and photomotor behavior were assessed across early development, followed by targeted cyp1a reporter analysis and transcriptomic profiling for a subset of potent exposures. Most chemicals induced morphological effects, with hydroxylated and sulfated metabolites producing effects more frequently and at lower benchmark concentrations than parent congeners. Behavioral alterations were more prevalent in embryonic photomotor response than larval photomotor response and generally co-occurred with morphological effects. Environmental mixtures elicited broad phenotypic profiles comparable to highly active individual compounds. Transcriptomic analyses revealed minimal responses for parent PCBs but robust, exposure-specific gene expression changes for select metabolites, particularly 5-OH-PCB11, and mixtures. Differentially expressed genes were enriched for xenobiotic metabolism, immune signaling, and neuroactive pathways, alongside consistent downregulation of circadian regulators. Together, these results demonstrate contributions of PCB metabolites and mixtures to toxicity.

metabolites

mixtures

neurotoxicity

polychlorinated biphenyls

transcriptomics

zebrafish

Details

Title: Subtitle: Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish
Creators: Nicole M. Breese - University of Iowa
Lisa Truong - Oregon State University
Xueshu Li - University of Iowa
Robyn L. Tanguay - Oregon State University
Hans-Joachim Lehmler - University of Iowa
Resource Type: Journal article
Publication Details: Toxics (Basel), Vol.14(5), 444
DOI: 10.3390/toxics14050444
PMID: 42198570
PMCID: PMC13211715
ISSN: 2305-6304
eISSN: 2305-6304
Publisher: MDPI
Grant note: National Institute of Environmental Health Sciences: P42ES013661, P42ES016465, R35ES031709 Iowa Superfund Research Program: P42ES013661
This research was funded by the National Institute of Environmental Health Sciences, grant numbers P42ES013661, P42ES016465, and R35ES031709. The PCB mixtures, individual PCBs, and PCB metabolites were provided by the Iowa Superfund Research Program, grant number P42ES013661.
Language: English
Date published: 05/19/2026
Academic Unit: Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9985164632202771

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