2. Academic Validation
  3. The crosstalk effects of polybrominated diphenyl ethers on the retinoic acid and thyroid hormone signaling pathway

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

  • Sci Total Environ. 2023 Apr 21;163590. doi: 10.1016/j.scitotenv.2023.163590.
Bin Zhang 1,  Fu Chen 2,  Ting Xu 3,  Yijun Tian 4,  Yajie Zhang 5,  Miao Cao 5,  Xueping Guo 5,  Daqiang Yin 6
Affiliations

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: [email protected].
  • 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.

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