Neurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation

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dc.authorid0000-0001-7094-3336
dc.authorid0000-0001-8705-9010
dc.authorid0000-0002-0881-5381
dc.authorid0000-0001-9163-927X
dc.authorid0000-0001-7665-7584
dc.contributor.authorWilson, Rebecca J.
dc.contributor.authorPanesar, Harmanpreet K.
dc.contributor.authorDursun, İlknur
dc.contributor.authorMendieta, Rosalia
dc.contributor.authorAndrew, Peter M.
dc.contributor.authorLi, Xueshu
dc.contributor.authorLehmler, Hans-Joachim
dc.contributor.authorLein, Pamela J.
dc.date.accessioned2026-07-24T12:07:36Z
dc.date.available2026-07-24T12:07:36Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.description.abstractPolychlorinated biphenyls (PCBs) pose a significant risk to the developing human brain, and recent epidemiological data suggest PCBs increase the risk and/or severity of neurodevelopmental disorders (NDD), including autism spectrum disorder (autism). Experimental animal studies confirm that PCBs disrupt neurodevelopment, resulting in behavioral deficits. Historically, research on the developmental neurotoxicity of PCBs has focused on the higher-chlorinated PCBs found in legacy commercial mixtures; however, lower-chlorinated PCBs (LC-PCBs), including congeners not present in commercial mixtures, predominate in contemporary human exposures. Previous in vitro studies demonstrated that one such LC-PCB, PCB 11, altered dendritic arborization, a cellular phenotype common to multiple NDD. Whether PCB 11 modulates dendritic morphogenesis in vivo is not known. In this study, we investigated how gestational and lactational exposure to PCB 11 in the maternal diet affected critical neurodevelopmental processes in juvenile male and female mice. C57BL/6J mouse dams were exposed to vehicle or PCB 11 at 0.1 or 1.0 mg/kg/d in their diet for 2 weeks prior to mating and throughout gestation and lactation. Brain tissue was collected from offspring at postnatal day (P)4 and P21 to assess dendritic arborization, apoptosis, glial reactivity, and neurogenesis in the hippocampus and neocortex. PCB 11 dose-dependently reduced the dendritic arborization of pyramidal neurons in the neocortex by 13-25% but had no significant effect on the dendritic morphogenesis of pyramidal neurons in the hippocampus. Apoptosis was not altered by PCB 11 in either brain region of either sex at either age. While PCB 11 had no effect on neurogenesis at P4, it dose-dependently decreased neurogenesis by 15-70% in the dentate gyrus at P21. GFAP immunoreactivity and the morphological complexity of astrocytes were increased by 40-60% and 20-60%, respectively, in the CA1 hippocampus of female mice exposed to 0.1 mg/kg/day PCB 11; in contrast, PCB 11 had no effect on IBA1 immunoreactivity. These findings demonstrate that developmental exposure to PCB 11 promoted NDD-relevant cellular phenotypes in a dose, sex, and region-dependent manner, providing experimental evidence in support of epidemiological data identifying PCBs as potential NDD risk modifiers. Ongoing studies are investigating behavioral responses in weanling mice developmentally exposed to PCB 11.
dc.identifier.citationWilson, R. J., Panesar, H. K., Dursun, İ., Mendieta, R., Andrew, P. M., Li, X., Lehmler, H. Jo., & Lein, P. J. (2026). Neurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation. Frontiers in Toxicology, 8, pp. 1-20. https://doi.org/10.3389/ftox.2026.1816944
dc.identifier.endpage20
dc.identifier.issn2673-3080
dc.identifier.pmidPMID: 42643987
dc.identifier.scopusqualityQ1
dc.identifier.startpage1
dc.identifier.urihttps://doi.org/10.3389/ftox.2026.1816944
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1558
dc.identifier.volume8
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherESCI - Emerging Sources Citation Index
dc.institutionauthorDursun, İlknur
dc.institutionauthorid0000-0001-7094-3336
dc.language.isoen
dc.publisherFrontiers Media S. A.
dc.relation.ispartofFrontiers in Toxicology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectApoptosis
dc.subjectDendritic Arborization
dc.subjectDevelopmental Neurotoxicity
dc.subjectGlial Reactivity
dc.subjectNeurodevelopmental Disorder
dc.subjectNeurogenesis
dc.subjectPolychlorinated Biphenyls
dc.titleNeurodevelopmental outcomes relevant to autism in juvenile mice exposed to PCB 11 in the maternal diet throughout gestation and lactation
dc.typeArticle
dspace.entity.typePublication

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