Thyroid disruption and the association with multi-toxicity endpoints in zebrafish embryos exposed to hymexazol

Thyroid hormone (TH) disruption during the early development of organisms is a critical mechanism underlying pesticide-induced toxicity. Hymexazol (HM), a widely used new-generation fungicide, poses environmental risks to aquatic ecosystems; however, its thyroid-disrupting potential remains poorly u...

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Main Authors: Lili Niu, Zhouchi Zhang, Kan Zhang, Zili Guo, Zeng Wang, Minhui Jin, Chao Xu, Jinsong Liu, Weiping Liu
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Ecotoxicology and Environmental Safety
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Online Access:http://www.sciencedirect.com/science/article/pii/S0147651325010425
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Summary:Thyroid hormone (TH) disruption during the early development of organisms is a critical mechanism underlying pesticide-induced toxicity. Hymexazol (HM), a widely used new-generation fungicide, poses environmental risks to aquatic ecosystems; however, its thyroid-disrupting potential remains poorly understood. In this study, we evaluated the thyroid disruption induced by HM and its interactions with developmental toxicity, melanin biosynthesis, and oxidative stress in zebrafish embryos. HM exposure significantly reduced TH levels and dysregulated key genes in the hypothalamic-pituitary-thyroid (HPT) axis, including DEIO1, DEIO2, TRα, TTR, and UGT1ab. Molecular docking analysis confirmed the high binding affinity of HM to TSHβ, supporting its role as a thyroid disruptor. The suppression of DEIO2 and subsequent TH depletion were closely associated with developmental abnormalities and impaired locomotor activity. HM exposure also reduced melanin deposition, with transcriptomic analysis revealing strong correlations between the expression of melanogenesis-related genes (MITFB and TYR) and TRα. Enrichment analysis showed interactions between the thyroid-related peroxisome proliferator-activated receptor (PPAR) signaling pathway and tyrosine metabolism, both of which are integral to melanin biosynthesis. Furthermore, HM induced oxidative stress, as evidenced by decreased activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), reduced levels of malondialdehyde (MDA) and glutathione (GSH), and increased Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) activity. Our findings elucidated complex interactions among TH regulation, developmental toxicity, melanin biosynthesis, and oxidative stress, improving the understanding of pesticide-induced endocrine disruption and its ecological implications.
ISSN:0147-6513