Hao Yanan, Liu Jing, Feng Yanni, Yu Shuai, Zhang Weidong, Li Lan, Min Lingjiang, Zhang Hongfu, Shen Wei, Zhao Yong
College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China.
Core Laboratories of Qingdao Agricultural University, Qingdao 266109, China.
Toxicol Appl Pharmacol. 2017 Aug 15;329:318-325. doi: 10.1016/j.taap.2017.06.021. Epub 2017 Jun 23.
Recently, reproductive, embryonic and developmental toxicity have been considered as one important sector of nanoparticle (NP) toxicology, with some studies already suggesting varying levels of toxicity and possible transgenerational toxic effects. Even though many studies have investigated the toxic effects of zinc oxide nanoparticles (ZnO NPs), little is known of their impact on overall reproductive outcome and transgenerational effects. Previously we found ZnO NPs caused liver dysfunction in lipid synthesis. This investigation, for the first time, explored the liver dysfunction at the molecular level of gene and protein expression in offspring after maternal exposure to ZnO NPs. Three pathways were investigated: lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis at 5 different time points from embryonic day-18 to postnatal day-20. It was found that the expression of 15, 16, and 16 genes in lipid synthesis, growth related factors and cell toxic biomarkers/apoptosis signalling pathway respectively in F1 animal liver were altered by ZnO NPs compared to ZnSO. The proteins in these signalling pathways (five in each pathways analyzed) in F1 animal liver were also changed by ZnO NPs compared to ZnSO. The results suggest that ZnO NPs caused maternal liver defects can also be detected in offspring that might result in problems on offspring liver development, mainly on lipid synthesis, growth, and lesions or apoptosis. Along with others, this study suggests that ZnO NPs may pose reproductive, embryonic and developmental toxicity; therefore, precautions should be taken with regard to human exposure during daily life.
最近，生殖、胚胎和发育毒性已被视为纳米颗粒（NP）毒理学的一个重要领域，一些研究已经表明存在不同程度的毒性以及可能的跨代毒性效应。尽管许多研究已经调查了氧化锌纳米颗粒（ZnO NPs）的毒性作用，但对其对整体生殖结果和跨代效应的影响却知之甚少。此前我们发现ZnO NPs会导致脂质合成中的肝功能障碍。本研究首次在母体暴露于ZnO NPs后，从基因和蛋白质表达的分子水平探索了子代的肝功能障碍。研究了三个途径：从胚胎第18天到出生后第20天的5个不同时间点的脂质合成、生长相关因子以及细胞毒性生物标志物/凋亡。结果发现，与硫酸锌相比，ZnO NPs改变了F1代动物肝脏中脂质合成、生长相关因子以及细胞毒性生物标志物/凋亡信号通路中分别有15、16和16个基因的表达。与硫酸锌相比，ZnO NPs也改变了F1代动物肝脏中这些信号通路中的蛋白质（每条通路分析5个）。结果表明，ZnO NPs导致的母体肝脏缺陷在子代中也能被检测到，这可能会导致子代肝脏发育问题，主要是在脂质合成、生长以及损伤或凋亡方面。与其他研究一起，本研究表明ZnO NPs可能具有生殖、胚胎和发育毒性；因此，在日常生活中应注意防范人类接触。
