Environmental levels of bis(2-ethylhexyl)-tetrabromophthalate (TBPH) cause thyroid toxicity and early carcinogenic signals in juvenile fish

文献类型： 外文期刊

第一作者： Hong, Xiang-sheng

作者： Hong, Xiang-sheng;Liu, Wang;Li, Zhi-tong;Wang, Juan;Yan, Sai-hong;Zha, Jin-miao;Yan, Liang;Zhao, Gao-feng;Sang, Wei;Ma, Xu-fa;Xin, Jia-jing;Liu, Wang;Li, Zhi-tong;Wang, Juan;Zha, Jin-miao

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关键词： Flame retardants; Endocrine disruption; Thyroid cancer; Gut microbiota; Transcriptome

期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：7.3； 五年影响因子：8.1 ）

ISSN： 0269-7491

年卷期： 2025 年 380 卷

页码：

收录情况： SCI

摘要： Exposure to novel brominated flame retardants (NBFRs) may engender thyroid dysfunction and even increase thyroid cancer risk. However, information regarding their thyroid toxic or disorder potential is primarily limited to thyroid hormone homeostasis. Here, we conducted a 28-day exposure experiment with juvenile rare minnows (Gobiocypris rarus) to 0.1-1000 mu g/L bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH, a NBFR), which preferentially accumulates in freshwater fish. First, molecular docking revealed the binding potential of TBPH to the thyroid receptor of the rare minnow. Subsequently, the results of hypothalamic-pituitary-thyroid axisrelated gene transcription patterns and thyroid hormone (TH) homeostasis indicated that TBPH could interfere with the TH conversion process. TBPH consequently altered thyroid morphology with more depleted follicles and reduced body weight. Transcriptomic profiling emphasized the vulnerability of thyroid function in juveniles, identifying the Ca2+/Rap1/mitogen-activated protein kinase axis as a potential pathway in TBPH-induced thyroid cancer. TBPH exposure increased the generation of new SNP sites in B-Raf proto-oncogene, serine/threonine kinase and changed the imbalance of intestinal flora, especially the proportion of Firmicutes and Bacteroidetes, which are closely associated with thyroid disease and cancer. Overall, our study provides evidence that TBPH exerts thyroid disruption and reveals for the first time the potential cause of increased thyroid cancer risk.

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