Silver nanoparticles (AgNPs) have been widely used as consumer products due to their antibacterial activities. Despite their extensive use, AgNPs have been reported to cause various types of cytotoxicity, including neurotoxicity. However, the potential action of AgNPs on early fetal development has not been elucidated. This study determined the effects of AgNPs on neural induction in human induced pluripotent stem cells (iPSCs), used as a model for human fetal stage development. It was observed that exposure to AgNPs reduced the expression of several neural differentiation marker genes, including OTX2, an early biomarker for neurogenesis in iPSCs. Since neural differentiation requires ATP as a source of energy, the intracellular ATP content was also measured. It was observed that AgNPs decreased intracellular ATP levels in iPSCs. Since AgNPs suppressed energy production, a critical mitochondrial function, the effects of AgNPs on mitochondrial dynamics were further studied. The results revealed that AgNPs induced mitochondrial fragmentation and reduced the level of mitochondrial fusion protein mitofusin 1 (Mfn1). Previously, we reported that knockdown of Mfn1 in iPSCs inhibited neural induction via OTX2 downregulation. This suggested that AgNPs could induce cytotoxicity, including neurodevelopmental toxicity, via Mfn1-mediated mitochondrial dysfunction in iPSCs. Thus, mitochondrial function in iPSCs can be used for assessing the cytotoxic effects associated with nanomaterials, including AgNPs.

中文翻译：

---

银纳米颗粒抑制人诱导的多能干细胞中的神经诱导

银纳米颗粒（AgNPs）由于其抗菌活性而被广泛用作消费产品。尽管已广泛使用，但据报道AgNP会引起多种类型的细胞毒性，包括神经毒性。但是，尚未阐明AgNPs对胎儿早期发育的潜在作用。这项研究确定了AgNPs对人类诱导的多能干细胞（iPSC）的神经诱导的影响，该细胞被用作人类胎儿阶段发育的模型。观察到暴露于AgNPs会降低一些神经分化标记基因的表达，包括OTX2，是iPSC中神经发生的早期生物标记。由于神经分化需要ATP作为能量来源，因此还测量了细胞内ATP含量。观察到AgNP降低了iPSC中的细胞内ATP水平。由于AgNPs抑制了能量产生，这是一种关键的线粒体功能，因此需要进一步研究AgNPs对线粒体动力学的影响。结果表明，AgNPs诱导线粒体片段化并降低了线粒体融合蛋白线粒体融合蛋白1（Mfn1）的水平。先前，我们报道了iPSC中Mfn1的敲低抑制了通过OTX2的神经诱导。下调。这表明AgNPs可以通过iPSCs中的Mfn1介导的线粒体功能障碍诱导细胞毒性，包括神经发育毒性。因此，iPSC中的线粒体功能可用于评估与包括AgNPs在内的纳米材料相关的细胞毒性作用。