Niu Lili, Zhang Zhouchi, Zhang Kan, Guo Zili, Wang Zeng, Jin Minhui, Xu Chao, Liu Jinsong, Liu Weiping
Zhejiang Collaborative Innovation Center for Full-Process Monitoring and Green Governance of Emerging Contaminants, Interdisciplinary Research Academy (IRA) and College of Biological and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, China.
Zhejiang Collaborative Innovation Center for Full-Process Monitoring and Green Governance of Emerging Contaminants, Interdisciplinary Research Academy (IRA) and College of Biological and Environmental Engineering, Zhejiang Shuren University, Hangzhou 310015, China; College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
Ecotoxicol Environ Saf. 2025 Sep 1;302:118697. doi: 10.1016/j.ecoenv.2025.118697. Epub 2025 Jul 18.
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.
生物体早期发育过程中的甲状腺激素（TH）紊乱是农药诱导毒性的关键机制。噁霉灵（HM）是一种广泛使用的新一代杀菌剂，对水生生态系统构成环境风险；然而，其甲状腺干扰潜力仍知之甚少。在本研究中，我们评估了HM诱导的甲状腺干扰及其与斑马鱼胚胎发育毒性、黑色素生物合成和氧化应激的相互作用。暴露于HM显著降低了TH水平，并使下丘脑-垂体-甲状腺（HPT）轴中的关键基因失调，包括DEIO1、DEIO2、TRα、TTR和UGT1ab。分子对接分析证实了HM与TSHβ的高结合亲和力，支持其作为甲状腺干扰物的作用。DEIO2的抑制和随后的TH耗竭与发育异常和运动活动受损密切相关。HM暴露还减少了黑色素沉积，转录组分析揭示了黑色素生成相关基因（MITFB和TYR）与TRα表达之间的强相关性。富集分析表明甲状腺相关的过氧化物酶体增殖物激活受体（PPAR）信号通路与酪氨酸代谢之间存在相互作用，这两者都是黑色素生物合成所必需的。此外，HM诱导了氧化应激，表现为抗氧化酶超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性降低、丙二醛（MDA）和谷胱甘肽（GSH）水平降低以及细胞色素P450家族1亚家族A成员1（CYP1A1）活性增加。我们的研究结果阐明了TH调节、发育毒性、黑色素生物合成和氧化应激之间的复杂相互作用，增进了对农药诱导的内分泌干扰及其生态影响的理解。
