Dose-dependent effects of silver nanoparticles on cell death modes in mouse blastocysts induced via endoplasmic reticulum stress and mitochondrial apoptosis.

IF 2.2 4区 医学 Q3 TOXICOLOGY
Toxicology Research Pub Date : 2024-10-03 eCollection Date: 2024-10-01 DOI:10.1093/toxres/tfae158
Cheng-Kai Lee, Fu-Ting Wang, Chien-Hsun Huang, Wen-Hsiung Chan
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Abstract

In view of the rapidly expanding medical and commercial applications of silver nanoparticles (AgNPs), their potential health risks and environmental effects are a significant growing concern. Earlier research by our group uncovered the embryotoxic potential of AgNPs, showing detrimental impacts of these nanoparticles on both pre- and post-implantation embryonic development. In the current study, we showed that low (50-100 μM) and high (200-400 μM) dose ranges of AgNPs trigger distinct cell death programs affecting mouse embryo development and further explored the underlying mechanisms. Treatment with low concentrations of AgNPs (50-100 μM) triggered ROS generation, in turn, inducing mitochondria-dependent apoptosis, and ultimately, harmful effects on embryo implantation, post-implantation development, and fetal development. Notably, high concentrations of AgNPs (200-400 μM) evoked more high-level ROS generation and endoplasmic reticulum (ER) stress-mediated necrosis. Interestingly, pre-incubation with Trolox, a strong antioxidant, reduced ROS generation in the group treated with 200-400 μM AgNPs to the level induced by 50-100 μM AgNPs, resulting in switching of the cell death mode from necrosis to apoptosis and a significant improvement in the impairment of embryonic development. Our findings additionally indicate that activation of PAK2 is a crucial step in AgNP-triggered apoptosis and sequent detrimental effects on embryonic development. Based on the collective results, we propose that the levels of ROS generated by AgNP treatment of embryos serve as a critical regulator of cell death type, leading to differential degrees of damage to embryo implantation, post-implantation development and fetal development through triggering apoptosis, necrosis or other cell death signaling cascades.

纳米银粒子对通过内质网应激和线粒体凋亡诱导的小鼠胚泡细胞死亡模式的剂量依赖性影响
鉴于银纳米粒子(AgNPs)的医疗和商业应用正在迅速扩大,其潜在的健康风险和环境影响日益受到人们的关注。我们小组的早期研究发现了银纳米粒子的胚胎毒性潜力,显示了这些纳米粒子对胚胎植入前和植入后发育的不利影响。在目前的研究中,我们发现低(50-100 μM)和高(200-400 μM)剂量范围的AgNPs会引发不同的细胞死亡程序,影响小鼠胚胎发育,并进一步探讨了其潜在机制。低浓度(50-100 μM)的AgNPs会引发ROS生成,进而诱导线粒体依赖性凋亡,最终对胚胎着床、着床后发育和胎儿发育产生有害影响。值得注意的是,高浓度的 AgNPs(200-400 μM)会诱发更高水平的 ROS 生成和内质网(ER)应激介导的坏死。有趣的是,用强抗氧化剂 Trolox 预孵育可将 200-400 μM AgNPs 处理组的 ROS 生成量降至 50-100 μM AgNPs 诱导的水平,从而使细胞死亡模式从坏死转向凋亡,并显著改善胚胎发育障碍。我们的研究结果还表明,PAK2 的活化是 AgNP 触发细胞凋亡并继而对胚胎发育产生不利影响的关键步骤。基于上述综合结果,我们提出,AgNP 处理胚胎所产生的 ROS 水平是细胞死亡类型的关键调节因子,通过引发细胞凋亡、坏死或其他细胞死亡信号级联,对胚胎植入、植入后发育和胎儿发育造成不同程度的损害。
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来源期刊
Toxicology Research
Toxicology Research TOXICOLOGY-
CiteScore
3.60
自引率
0.00%
发文量
82
期刊介绍: A multi-disciplinary journal covering the best research in both fundamental and applied aspects of toxicology
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