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

• DOI: 10.1021/acs.est.4c06287
• Publication Date: 2024-10-03T07:40:09Z
• Authors: Xiushuai Du; Xueming Xu; Hongjie Yu; Zhiyuan Du; Yitian Wu; Kelei Qian; Jing Xu; Gonghua Tao; Ling Zhang; Weiwei Zheng
• Keywords: Male; Fluorocarbons; China; Thyroid Gland; Humans; Animals; Female; Environmental Pollutants; Environmental Exposure; Endocrine Disruptors; Toxicogenetics

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