The crosstalk effects of polybrominated diphenyl ethers on the retinoic acid and thyroid hormone signaling pathway

Bin Zhang; Fu Chen; Ting Xu; Yijun Tian; Yajie Zhang; Miao Cao; Xueping Guo; Daqiang Yin

doi:10.1016/j.scitotenv.2023.163590

The crosstalk effects of polybrominated diphenyl ethers on the retinoic acid and thyroid hormone signaling pathway

Sci Total Environ. 2023 Jul 20:883:163590. doi: 10.1016/j.scitotenv.2023.163590. Epub 2023 Apr 23.

Authors

Bin Zhang¹, Fu Chen², Ting Xu³, Yijun Tian⁴, Yajie Zhang⁵, Miao Cao⁵, Xueping Guo⁵, Daqiang Yin⁶

Affiliations

¹ Department of Health Toxicology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China; Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
² School of Environmental and Geographical Sciences, Shanghai Normal University, Shanghai 200234, China.
³ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address: xuting@tongji.edu.cn.
⁴ Department of Health Toxicology, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
⁵ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China.
⁶ Key Laboratory of Yangtze River Water Environment, Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China.

PMID: 37088389
DOI: 10.1016/j.scitotenv.2023.163590

Abstract

The toxicological and pathological influences of polybrominated diphenyl ethers (PBDEs) on the animal central nervous system have attracted worldwide attention. However, their mechanism of action has not been completely elucidated. Given that retinoic acid (RA) and thyroid hormone (TH) signaling pathway are closely related to neurodevelopment, the crosstalk between the two signaling pathways at the levels of metabolite conversion, gene expression and ligand-receptor interaction after exposure to two representative PBDE congeners (BDE-47 and BDE-209) using zebrafish larvae, dual reporter gene assay, and docking simulation was studied. Our results clarified that BDE-47 could disrupt the transport and metabolism of retinoids, induce changes in expression of key genes, bind with the seven nuclear receptors, and activate RA signaling pathway. BDE-47 exhibited more effects on the indicators of the two signaling pathways than BDE-209. Furthermore, BDE-47 may disrupt TH signaling pathway by disrupting RA signaling pathway, indicating that RA signal is priorly influenced than TH signal. This work offered a new perspective to elucidate TH signal disruption mechanism induced by PBDEs from RA signaling pathway, which is of great significance to elucidate the health effects of PBDEs.

Keywords: Endocrine disruption; Neurodevelopmental toxicity; PBDEs; Retinoic acid signaling pathway.

MeSH terms

Animals
Halogenated Diphenyl Ethers* / metabolism
Halogenated Diphenyl Ethers* / toxicity
Signal Transduction
Thyroid Hormones / metabolism
Tretinoin / metabolism
Tretinoin / toxicity
Zebrafish* / metabolism

Substances

decabromobiphenyl ether
2,2',4,4'-tetrabromodiphenyl ether
Halogenated Diphenyl Ethers
Tretinoin
Thyroid Hormones