Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

Marić, Đurđica; Baralić, Katarina; Vukelić, Dragana; Milošević, Ivan; Nikolić, Anja; Antonijević, Biljana; Đukić-Ćosić, Danijela; Bulat, Zorica; Aschner, Michael; Djordjevic, Aleksandra Buha

doi:10.1016/j.chemosphere.2024.142441

Chemosphere

2024

DOI: 10.1016/j.chemosphere.2024.142441

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Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

Đurđica Marić,

Katarina Baralić,

Dragana Vukelić

et al.

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Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets

Du,

Xu,

et al. 2024

Environ. Sci. Technol.

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Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are emerging environmental endocrine disruptors that may adversely affect the human endocrine system, particularly the thyroid gland, the largest endocrine gland in the human body. An epidemiologic survey was conducted involving 318 community residents in Shanghai, China, to assess PFAS exposure levels. The relationship between PFAS exposure and five thyroid function indicators was analyzed using Bayesian Kernel Regression (BKMR) and Weighted Quantile Sum Regression (WQS). Ten effector genes related to PFAS and thyroid diseases were identified through the Comparative Toxicogenomics Database (CTD) for bioinformatics analysis and pathways involved were explored through mediation analysis. In vivo validation of these effector genes was conducted using PCR, complemented by in vitro cellular experiments involving transcriptome sequencing and the construction of animal models to simulate mixed PFAS exposure in the general population. Mixed PFAS exposure was found to impact thyroid health primarily through pathways related to lipid metabolism in toxicogenomic studies and resulted in the upregulation of key genes associated with lipid metabolism in animal models. Our results demonstrate that PFAS exposure could affect the expression of lipid metabolism pathways through the modulation of transcription factors, contributing to the development of thyroid disease.

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Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets

Du,

Xu,

et al. 2024

Environ. Sci. Technol.

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show abstract

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Thyroid under siege: Unravelling the toxic impact of real-life metal mixture exposures in Wistar rats

Cited by 1 publication

References 76 publications

Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets

Thyrotoxic Effects of Mixed Exposure to Perfluorinated Compounds: Integrating Population-Based, Toxicogenomic, Animal, and Cellular Evidence to Elucidate Molecular Mechanisms and Identify Potential Effector Targets

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