Bisphenol analogues induce thyroid dysfunction via the disruption of the thyroid hormone synthesis pathway

Chao Hu; Yeqing Xu; Mingmin Wang; Shixuan Cui; Hangjun Zhang; Liping Lu

doi:10.1016/j.scitotenv.2023.165711

Bisphenol analogues induce thyroid dysfunction via the disruption of the thyroid hormone synthesis pathway

Sci Total Environ. 2023 Nov 20:900:165711. doi: 10.1016/j.scitotenv.2023.165711. Epub 2023 Jul 23.

Authors

Chao Hu¹, Yeqing Xu², Mingmin Wang³, Shixuan Cui⁴, Hangjun Zhang⁵, Liping Lu⁶

Affiliations

¹ School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China; School of Engineering, Hangzhou Normal University, Hangzhou 310018, China.
² School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
³ The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
⁴ College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
⁵ School of Engineering, Hangzhou Normal University, Hangzhou 310018, China; Hangzhou International Urbanology Research Center, Hangzhou 311121, China.
⁶ School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: lipinglu@hznu.edu.cn.

PMID: 37487893
DOI: 10.1016/j.scitotenv.2023.165711

Abstract

Bisphenol analogues are widely used in industrial and daily-use consumer products having imperfect thyroid hormones (THs) structures. Widespread exposure interferes with thyroid-related health outcomes in human. The mechanisms of disruption on TH synthesis and subsequent thyroid dysfunction by different bisphenol analogues remain unclear. Here, we evaluated bisphenol-induced thyroid endocrine disruption in C57BL/6 mice at doses of 0.002, 0.02, 2, and 20 mg/kg body weight/day (BW/d) for five consecutive weeks. Administration of 20 mg/kg BW/d bisphenol S (BPS) and 2 mg/kg BW/d tetrabromobisphenol S (TBBPS) significantly increased serum thyrotropin (TSH) levels to 1.21-fold and 1.20-fold of control group, respectively, indicating that bisphenols induced thyroid dysfunction in mice. Height of the thyroid follicle epithelium significantly increased to 1.27-, 1.24-, 1.26-, and 1.36-fold compared to control group with BPA, BPS, TBBPA, and TBBPS at 20 mg/kg BW/d, respectively, indicating impairment of the thyroid gland structure, and TBBPS showed potent effect. Exposure to bisphenol analogues of 0.02 mg/kg BW/d downregulated the protein expression levels of thyrotropin receptor, the sodium/iodide symporter, thyroperoxidase. The TH-dependent effects were further determined using the T-Screen assay at 10^-11 M to 10^-5 M concentrations. Bisphenol analogues significantly decreased TH-dependent GH3 cell proliferation, indicating the antagonistic activity of bisphenol analogues. The gene responsible for THs synthesis of thyrotropin releasing hormone receptor and TSH were upregulated, but downregulation of thyroid receptor β was observed. Our results suggest that bisphenol analogues distinctly induce thyroid dysfunction via TH synthesis, implying adverse effect of bisphenol analogues on TH homeostasis and subsequent physiological processes.

Keywords: Bisphenol analogues; T-screen assay; Thyroid disruption; Thyroid hormone synthesis.

MeSH terms

Animals
Benzhydryl Compounds / toxicity
Humans
Mice
Mice, Inbred C57BL
Thyroid Gland* / metabolism
Thyroid Hormones* / metabolism
Thyrotropin

Substances

tetrabromobisphenol S
Thyroid Hormones
bisphenol A
Benzhydryl Compounds
Thyrotropin