State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
Sci Total Environ. 2020 Jul 10;725:138433. doi: 10.1016/j.scitotenv.2020.138433. Epub 2020 Apr 6.
Silver nanoparticles (AgNPs) are commonly utilized industrial compounds mostly because of their antimicrobial properties. Nevertheless, our understanding of their potential developmental toxicity in humans is still limited. Embryonic stem cells (ESCs) are powerful in vitro tools for developmental toxicity assessments of chemicals. Here, we evaluated the potential developmental toxicity during early embryogenesis of AgNPs and AgNO with human ESC (hESC)-based differentiation systems in vitro. We found that human relevant concentrations of AgNPs and Ag ions affected the specification of two of the three primary germ layers, endoderm and mesoderm, without drastically affecting ectoderm. Furthermore, the two forms of Ag impaired the generation and functions of hepatocytes-like cells derived from endoderm, by decreasing the expression of important liver markers such as AFP, ALB, and HNF4A, and altering glycogen storage. When considering cardiac development, AgNPs and AgNO manifested opposite adverse effects, in that AgNPs increased while AgNO decreased the expression of typical cardiac markers (NKX2.5, MYH6, and ISL) in hESC-derived cardiomyocytes. In conclusion, our findings argue for a potential developmental toxicity of AgNP doses we are exposed to, or levels detected in the human body, especially at very early stages during embryogenesis, and which may not be just due to Ag leakage. Moreover, mesendoderm-derived cell types, tissues and organs may be more prone to AgNP toxicity than ectoderm lineages.
银纳米粒子（AgNPs）是一种常用的工业化合物，主要因其具有抗菌性能而被广泛应用。然而，我们对其在人类体内潜在发育毒性的了解仍然有限。胚胎干细胞（ESCs）是评估化学物质发育毒性的有力体外工具。在这里，我们使用基于人胚胎干细胞（hESC）的分化系统，在体外评估了 AgNPs 和 AgNO 在早期胚胎发生过程中的潜在发育毒性。我们发现，人类相关浓度的 AgNPs 和 Ag 离子会影响三个原肠胚层中的两个（内胚层和中胚层）的特化，而对外胚层的影响不大。此外，这两种形式的 Ag 会通过降低 AFP、ALB 和 HNF4A 等重要肝脏标志物的表达，并改变糖原储存，损害内胚层衍生的肝样细胞的生成和功能。当考虑心脏发育时，AgNPs 和 AgNO 表现出相反的不良影响，即 AgNPs 增加而 AgNO 降低 hESC 衍生的心肌细胞中典型的心脏标志物（NKX2.5、MYH6 和 ISL）的表达。总之，我们的研究结果表明，AgNP 剂量或在人体中检测到的 Ag 水平可能具有潜在的发育毒性，尤其是在胚胎发生的早期阶段，而且这种毒性可能不仅仅是由于 Ag 的泄漏所致。此外，中胚层衍生的细胞类型、组织和器官可能比外胚层谱系更容易受到 AgNP 毒性的影响。
