Abstract：
In the real environment, some chemical functional groups are unavoidably combined on the nanoplastic surface. Reportedly, amino-modified polystyrene nanoparticles (PS-A NPs) exposure in parents can induce severe transgenerational toxicity, but the underlying molecular mechanisms remain largely unclear. Using Caenorhabditis elegans as the animal model, this study was performed to investigate the role of germline epidermal growth factor (EGF) signal on modulating PS-A NPs\' transgenerational toxicity. As a result, 1-10 μg/L PS-A NPs exposure transgenerationally enhanced germline EGF ligand/LIN-3 and NSH-1 levels. Germline RNAi of lin-3 and nsh-1 was resistant against PS-A NPs\' transgenerational toxicity, implying the involvement of EGF ligand activation in inducing PS-A NPs\' transgenerational toxicity. Furthermore, LIN-3 overexpression transgenerationally enhanced EGF receptor/LET-23 expression in the progeny, and let-23 RNAi in F1-generation notably suppressed PS-A NPs\' transgenerational toxicity in the exposed worms overexpressing germline LIN-3 at P0 generation. Finally, LET-23 functioned in neurons and intestine for regulating PS-A NPs\' transgenerational toxicity. LET-23 acted at the upstream DAF-16/FOXO within the intestine in response to PS-A NPs\' transgenerational toxicity. In neurons, LET-23 functioned at the upstream of DAF-7/DBL-1, ligands of TGF-β signals, to mediate PS-A NPs\' transgenerational toxicity. Briefly, this work revealed the exposure risk of PS-A NPs\' transgenerational toxicity, which was regulated through activating germline EGF signal in organisms.
摘要：
在现实环境中,一些化学官能团不可避免地结合在纳米塑料表面上。据报道,氨基改性聚苯乙烯纳米粒子（PS-ANPs）在父母中的暴露可引起严重的跨代毒性，但潜在的分子机制仍不清楚。以秀丽隐杆线虫为动物模型,本研究旨在研究种系表皮生长因子(EGF)信号在调节PS-ANP的跨代毒性中的作用。因此,1-10μg/LPS-ANP暴露跨代增强种系EGF配体/LIN-3和NSH-1水平。lin-3和nsh-1的种系RNAi对PS-ANP的跨代毒性具有抗性，暗示EGF配体激活参与诱导PS-ANP的跨代毒性。此外，LIN-3过表达在后代中代际增强EGF受体/LET-23表达，F1代中的let-23RNAi显着抑制了P0代过表达种系LIN-3的暴露蠕虫中的PS-ANP的跨代毒性。最后,LET-23在神经元和肠道中发挥作用，调节PS-ANP的跨代毒性。LET-23在肠道内的上游DAF-16/FOXO起作用，以响应PS-ANP的跨代毒性。在神经元中，LET-23在DAF-7/DBL-1（TGF-β信号的配体）的上游起作用，介导PS-ANP的跨代毒性。简而言之，这项工作揭示了PS-ANPs跨代毒性的暴露风险，通过激活生物体中的种系EGF信号来调节。
