Wang Dou, Wang Yihan, Mao Liangang, Liu Xinju, Chen Chen, Wang Yanhua, Yang Guiling
State Key Laboratory for Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Ecotoxicol Environ Saf. 2025 Sep 1;302:118740. doi: 10.1016/j.ecoenv.2025.118740. Epub 2025 Jul 23.
The widespread agricultural use of dimethomorph (DMO) and difenoconazole (DFC) leads to their frequent joint detection in aquatic environments. However, their combined transgenerational toxicological impacts remain largely unexplored. This study delved into the combined effects of DMO and DFC on zebrafish (Danio rerio) across multiple generations. Based on the 96-hour LC values obtained from zebrafish embryo acute toxicity tests, chronic exposure concentrations were established (DMO: 0.0114 mg/L; DFC: 0.0049 mg/L). Parental zebrafish (F0 generation) were exposed for 60 days prior to breeding, followed by a 7-day exposure of their F1 offspring to evaluate the transgenerational effects of individual and combined pesticides. F0 exposure precipitated pronounced oxidative stress, apoptosis, and dysregulation of key detoxification enzyme activities, including significant alterations in malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), Caspase-3, carboxylesterase (CarE), and glutathione S-transferase (GST). Intriguingly, these biochemical perturbations persisted in F1 progeny with amplified effects under continued exposure. Moreover, co-exposure elicited endocrine disruption, evidenced by elevated thyroid hormone levels (T3 and T4) and the upregulation of vtg, crh, and tshb transcripts, implicating profound dysregulation of the hypothalamic-pituitary-thyroid (HPT) axis. Our findings demonstrated that DMO and DFC induce significant toxicological effects in zebrafish, affecting both the directly exposed parental generation (F0) and their unexposed offspring (F1), offering critical insights for safeguarding aquatic biodiversity.
二甲嘧菌胺（DMO）和苯醚甲环唑（DFC）在农业中的广泛使用导致它们在水生环境中经常被联合检测到。然而，它们的联合跨代毒理学影响在很大程度上仍未得到探索。本研究深入探讨了DMO和DFC对斑马鱼（Danio rerio）多代的联合影响。根据斑马鱼胚胎急性毒性试验获得的96小时LC值，确定了慢性暴露浓度（DMO：0.0114 mg/L；DFC：0.0049 mg/L）。亲代斑马鱼（F0代）在繁殖前暴露60天，然后其F1代后代暴露7天，以评估单一农药和混合农药的跨代影响。F0暴露引发了明显的氧化应激、细胞凋亡和关键解毒酶活性的失调，包括丙二醛（MDA）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、半胱天冬酶-3、羧酸酯酶（CarE）和谷胱甘肽S-转移酶（GST）的显著变化。有趣的是，这些生化扰动在F1后代中持续存在，并且在持续暴露下影响加剧。此外，联合暴露引发了内分泌干扰，表现为甲状腺激素水平（T3和T4）升高以及vtg、crh和tshb转录本上调，这意味着下丘脑-垂体-甲状腺（HPT）轴存在严重失调。我们的研究结果表明，DMO和DFC对斑马鱼具有显著的毒理学影响，不仅影响直接暴露的亲代（F0），还影响未暴露的后代（F1），为保护水生生物多样性提供了重要见解。
