As an emerging pollutant frequently detected in aquatic ecosystems, the toxicity of N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone (6PPD-quinone) on fish has been confirmed, but insight into the mechanisms underlying those adverse effects is still limited. Thus, we exposed zebrafish embryos to 6PPD-quinone at 0, 0.25, 2.5, and 25 μg/L until 120 h post-fertilization (hpf), and investigated the variations in their development, behavior, monoamine neurotransmitter levels, and transcriptional profile. Exposure to 6PPD-quinone notably elevated the heart rate of zebrafish at 48 hpf (at 2.5 and 25 μg/L) and 72 hpf (at 0.25, 2.5, and 25 μg/L). In the dark-light transition test, the locomotor activity of zebrafish larvae exposed to 6PPD-quinone significantly increased, especially in the dark periods. Exposure to 6PPD-quinone also altered the dopamine level and its turnover in zebrafish, which exhibited significant correlations to their locomotor activity. RNA sequencing identified 394 differentially expressed genes (DEGs), most of which have the molecular function of binding and catalytic activity. Five DEGs were predicted as the key driver genes in the protein-protein interaction networks associated with circadian rhythm (i.e., npas2), protein processing in endoplasmic reticulum (i.e., hsp90b1 and pdia4), and estrogen signaling pathway (i.e., hsp90aa1.1 and hsp90aa1.2). Our findings provide more insights into mechanisms underlying the toxicity of 6PPD-quinone to teleosts and highlight the necessity to assess its potential risks to aquatic ecosystems.

中文翻译：

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基于 6PPD-醌对斑马鱼早期生命阶段神经行为影响的机制的转录组学分析


作为水生生态系统中经常检测到的新兴污染物，N-（1,3-二甲基丁基）-N'-苯基-对苯二胺-醌（6PPD-醌）对鱼类的毒性已得到证实，但对这些不利影响的潜在机制的了解仍然有限。因此，我们将斑马鱼胚胎暴露于 0、0.25、2.5 和 25 μg/L 的 6PPD-醌中，直至受精后 120 小时 （hpf），并研究其发育、行为、单胺神经递质水平和转录谱的变化。暴露于 6PPD-醌显着提高了斑马鱼的心率，达到 48 hpf（2.5 和 25 μg/L）和 72 hpf（0.25、2.5 和 25 μg/L）。在暗光过渡试验中，暴露于 6PPD-醌的斑马鱼幼虫的运动活性显著增加，尤其是在黑暗时期。暴露于 6PPD-醌还改变了斑马鱼的多巴胺水平及其周转率，这与它们的运动活动表现出显着相关性。RNA 测序鉴定出 394 个差异表达基因 （DEGs），其中大多数具有结合和催化活性的分子功能。预测 5 个 DEGs 是与昼夜节律 （即 npas2）、内质网中蛋白质加工 （即 hsp90b1 和 pdia4） 和雌激素信号通路 （即 hsp90aa1.1 和 hsp90aa1.2） 相关的蛋白质-蛋白质相互作用网络中的关键驱动基因。我们的研究结果为 6PPD-醌对硬骨动物毒性的潜在机制提供了更多见解，并强调了评估其对水生生态系统潜在风险的必要性。