The toxicity of 6-PPD quinone (6-PPDQ) has been frequently detected. However, the possible transgenerational effects of 6-PPDQ remain largely unclear. Due to short life cycle and high sensitivity to environmental exposure, Caenorhabditis elegans is useful for study of transgenerational toxicology. In C. elegans, we observed the transgenerational increase in lipid accumulation after parental generation (P0-G) exposure to 6-PPDQ at 0.1–10 μg/L. Accompanied with this, transgenerational increase in expressions of genes governing fatty acid synthesis and monounsaturated fatty acyl-CoAs synthesis and decrease in genes governing fatty acid β-oxidation were induced by 6-PPDQ exposure. Moreover, 6-PPDQ exposure at P0-G caused transgenerational activation of mdt-15 and sbp-1 encoding lipid metabolic sensors. Meanwhile, exposure to 6-PPDQ induced transgenerational activation of set-2 and inhibition in rbr-2, two genes encoding components of COMPASS complex. The 6-PPDQ induced transgenerational lipid accumulation could be strengthened by RNAi of set-2 and suppressed by RNAi of rbr-2. Additionally, 6-PPDQ induced transgenerational neurotoxicity could be increased by RNAi of mdt-15, sbp-1, and rbr-2, and inhibited by RNAi of set-2. Therefore, our results demonstrated the possibility in resulting in transgenerational lipid accumulation by exposure to 6-PPDQ.

中文翻译：

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6-PPD 醌导致多代脂质积累，受秀丽隐杆线虫中代谢传感器和 COMPASS 复合物成分的影响不同


6-PPD 醌 （6-PPDQ） 的毒性已经常被检测到。然而，6-PPDQ 可能的跨代影响在很大程度上仍不清楚。由于生命周期短且对环境暴露高度敏感，秀丽隐杆线虫可用于跨代毒理学研究。在秀丽隐杆线虫中，我们观察到亲代 （P0-G） 暴露于 0.1-10 μg/L 的 6-PPDQ 后脂质积累的跨代增加。与此同时，6-PPDQ 暴露诱导了控制脂肪酸合成和单不饱和脂肪酰基辅酶 A 合成的基因表达的跨代增加以及控制脂肪酸β-氧化的基因的减少。此外，P0-G 的 6-PPDQ 暴露导致编码脂质代谢传感器的 mdt-15 和 sbp-1 的跨代激活。同时，暴露于 6-PPDQ 诱导 set-2 的跨代激活和 rbr-2 的抑制，这两个基因编码 COMPASS 复合物的成分。set-2 的 RNAi 可加强 6-PPDQ 诱导的跨反代脂质积累，而 rbr-2 的 RNAi 可抑制 6-PPDQ 诱导的跨反代脂质积累。此外，mdt-15 、 sbp-1 和 rbr-2 的 RNAi 可增加 6-PPDQ 诱导的跨代神经毒性，而 set-2 的 RNAi 可抑制 6-PPDQ 诱导的跨代神经毒性。因此，我们的结果表明了暴露于 6-PPDQ 导致跨代脂质积累的可能性。