Cytochrome P450 Expression Influences Behavioral Responses to 3,3'-Dichlorobiphenyl (PCB 11) in Juvenile Male and Female Mice Exposed Throughout Gestation and Lactation

Rebecca J Wilson; Crystal M Roach; Rosalia Mendieta; Anthony E Valenzuela; Yi-Hua Tsai; Xueshu Li; Xinxin Ding; Hans-Joachim Lehmler; Pamela J Lein

doi:10.1016/j.neuro.2026.103585

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Cytochrome P450 Expression Influences Behavioral Responses to 3,3'-Dichlorobiphenyl (PCB 11) in Juvenile Male and Female Mice Exposed Throughout Gestation and Lactation

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Cytochrome P450 Expression Influences Behavioral Responses to 3,3'-Dichlorobiphenyl (PCB 11) in Juvenile Male and Female Mice Exposed Throughout Gestation and Lactation

Rebecca J Wilson, Crystal M Roach, Rosalia Mendieta, Anthony E Valenzuela, Yi-Hua Tsai, Xueshu Li, Xinxin Ding, Hans-Joachim Lehmler and Pamela J Lein

Neurotoxicology (Park Forest South), Vol.117, 103585

10/04/2026

DOI: 10.1016/j.neuro.2026.103585

PMID: 42830136

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Abstract

While legacy higher-chlorinated PCBs are widely accepted to be developmental neurotoxicants that cause cognitive deficits, virtually nothing is known about the developmental neurotoxicity (DNT) potential of lower-chlorinated (LC) PCBs. Additionally, the influence of metabolism on DNT outcomes is largely unknown despite evidence that toxicity can vary between parent congeners and their metabolites. To address these critical gaps, we examined behavioral outcomes in juvenile mice exposed to PCB 11, a prevalent LC-PCB, at 0, 0.1, 1 or 6mg/kg/d in the maternal diet throughout gestation and lactation. Behavior was compared between mice with distinct cytochrome P450 (CYP) profiles: wildtype (WT) C57BL/6J, Cyp2abfgs gene cluster knockout (CYP-Null), and CYP-Null that express human CYP2A6 (2A6-Hum). PCB 11 increased body weight in WT pups and CYP-Null and 2A6-Hum dams but did not alter other indices of maternal and pup toxicity. PCB 11 reduced ultrasonic vocalizations in WT and 2A6-Hum but not CYP-Null pups. CYP-Null mice exposed to 0.1 and 6.0mg/kg/d PCB 11 showed increased exploratory behavior, whereas WT and 2A6-Hum mice were unaffected. Genotype-, PCB 11 dose-, and sex-dependent impairments in sociability, social novelty, and novel object recognition memory but not spontaneous alternation were observed. PCB 11 metabolites but not the parent congener were detected in serum from P21 pups in the 6.0mg/kg/d dose group only; neither PCB 11 nor its metabolites were detected in P35 serum. These findings suggest that developmental PCB 11 exposure alters social and cognitive behavior, and that CYP-mediated metabolism modifies susceptibility to PCB-induced DNT.

Metabolism

lower chlorinated polychlorinated biphenyls

social behavior

cytochrome P450 enzymes

recognition memory

social communication

Details

Title: Subtitle: Cytochrome P450 Expression Influences Behavioral Responses to 3,3'-Dichlorobiphenyl (PCB 11) in Juvenile Male and Female Mice Exposed Throughout Gestation and Lactation
Creators: Rebecca J Wilson - University of California, Davis
Crystal M Roach - University of Iowa
Rosalia Mendieta - University of California, Davis
Anthony E Valenzuela - University of California, Davis
Yi-Hua Tsai - University of California, Davis
Xueshu Li - University of Iowa
Xinxin Ding - University of Arizona
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA, USA. Electronic address: hans-joachim-lehmler@uiowa.edu
Pamela J Lein - University of California, Davis
Resource Type: Journal article
Publication Details: Neurotoxicology (Park Forest South), Vol.117, 103585
DOI: 10.1016/j.neuro.2026.103585
PMID: 42830136
ISSN: 0161-813X
eISSN: 1872-9711
Publisher: Elsevier
Grant note: National Institute of Environmental Health: R01 ES014901, R01 ES031098 UC Davis Emmy Werner and Stanley Jacobsen Fellowship UC Davis Professors for the Future Fellowship Program NIH: T32 GM135741, T32 ES007059 Southwest Environmental Health Sciences Center: P30 ES006694 Environmental Health Sciences Research Center at the University of Iowa: P30 ES005605
This work was supported by the National Institute of Environmental Health [grant numbers R01 ES014901 and R01 ES031098] . Dr. Rebecca J Wilson was supported in part by the UC Davis Emmy Werner and Stanley Jacobsen Fellowship and the UC Davis Professors for the Future Fellowship Program. Rosalia Mendieta was supported by NIH-funded training grants (T32 GM135741 and T32 ES007059) . The maintenance of CYP transgenic and knockout mouse strains at the University of Arizona was supported in part by the Southwest Environmental Health Sciences Center (grant number P30 ES006694) ; PCB 11 synthesis and analysis were supported in part by the Environmental Health Sciences Research Center at the University of Iowa (grant number P30 ES005605) . The contents of this study do not necessarily represent the official views of the NIH, and the NIH does not endorse the purchase of any commercial products or services mentioned in the publication.
Language: English
Electronic publication date: 10/04/2026
Academic Unit: Public Health Administration; Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9985242782502771

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