Liu Wei, Yang Yanlei, Han Jingyu, Feng Yiyi, Ma Junguo, Li Xiaoyu
Pingyuan Laboratory, State Key Laboratory of Antiviral Drugs, College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Henan International Joint Laboratory of Aquatic Toxicology and Health Protection, Henan Normal University, Xinxiang, Henan 453007, China.
Ecotoxicol Environ Saf. 2025 Sep 1;302:118678. doi: 10.1016/j.ecoenv.2025.118678. Epub 2025 Jul 16.
The coexistence of glyphosate (GLY) and microcystin-LR (MC-LR) in the environment has become a problem that cannot be ignored. However, the combined toxic effects of these compounds on aquatic organisms remain underexplored. The purpose of this study was to evaluate the individual and combined effects of GLY and MC-LR on the neurobehavior of exposed adult zebrafish and their untreated offspring (F1 larvae), as well as to explore the underlying mechanisms. In this study, six month old male zebrafish were exposed to 3.5 mg/L GLY and 35 μg/L MC-LR, alone and in combination, for 21 d. The results revealed that exposure to GLY and/or MC-LR decreased locomotor activity, heightened anxiety-like behaviors, and disrupted social interactions in adult zebrafish, thereby confirming their neurotoxic effects. Pathological damage, along with elevated levels of ROS, IL-1β, and caspase-3, were observed in the brains of the treated fish. RNA-seq analysis further revealed that GLY and/or MC-LR treatment induced widespread transcriptional changes in the zebrafish brain, potentially impacting a range of biological functions, including neurobehavior. Meanwhile, paternal exposure to GLY and MC-LR, either individually or in combination, inhibited the spontaneous movement of untreated embryos at 24 hpf and reduced swimming activity at 120 hpf. Transcriptome sequencing of larvae further elucidates the intricate mechanisms underlying the intergenerational neurotoxicity induced by GLY and/or MC-LR, and the metabolic alterations potentially play an important role in mediating this toxicity. Overall, these findings collectively provide robust evidence of intergenerational effects resulting from exposure to individual and combined GLY and MC-LR, especially regarding persistent impacts on behavioral parameters, which should be emphasized in future ecological and health risk assessments.
环境中草甘膦（GLY）和微囊藻毒素-LR（MC-LR）的共存已成为一个不可忽视的问题。然而，这些化合物对水生生物的联合毒性作用仍未得到充分研究。本研究的目的是评估GLY和MC-LR对暴露的成年斑马鱼及其未处理后代（F1幼虫）神经行为的单独和联合影响，并探索其潜在机制。在本研究中，将6个月大的雄性斑马鱼单独或联合暴露于3.5mg/L的GLY和35μg/L的MC-LR中，持续21天。结果显示，暴露于GLY和/或MC-LR会降低成年斑马鱼的运动活性，增加焦虑样行为，并破坏社交互动，从而证实了它们的神经毒性作用。在处理过的鱼的大脑中观察到病理损伤，以及活性氧、白细胞介素-1β和半胱天冬酶-3水平的升高。RNA测序分析进一步表明，GLY和/或MC-LR处理会诱导斑马鱼大脑中广泛的转录变化，可能影响一系列生物学功能，包括神经行为。同时，父本暴露于GLY和MC-LR，单独或联合暴露，会抑制未处理胚胎在24小时胚胎期的自发运动，并降低120小时胚胎期的游泳活性。幼虫的转录组测序进一步阐明了GLY和/或MC-LR诱导的代际神经毒性的复杂机制，代谢改变可能在介导这种毒性中起重要作用。总体而言，这些发现共同提供了有力证据，证明暴露于单独和联合的GLY和MC-LR会产生代际影响，特别是对行为参数的持续影响，这在未来的生态和健康风险评估中应予以重视。
