Journal article
Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish
Toxics (Basel), Vol.14(5), 444
05/19/2026
DOI: 10.3390/toxics14050444
PMCID: PMC13211715
PMID: 42198570
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.
Details
- Title: Subtitle
- Morphological, Behavioral, and Transcriptomic Profiling Reveals Developmental Toxicity of PCB Metabolites in Zebrafish
- Creators
- Nicole M. Breese - University of IowaLisa Truong - Oregon State UniversityXueshu Li - University of IowaRobyn L. Tanguay - Oregon State UniversityHans-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
- NLM abbreviation
- Toxics
- 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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