Silver Nanoparticles Induce TET-Dependent Genome-Wide DNA Hydroxymethylation Alterations in Mouse Embryonic Stem Cells via Reactive Oxygen Species Signaling

Exposure to silver nanoparticles (AgNPs) poses potential health risks. Epigenetic alterations are increasingly recognized as a critical mechanistic bridge between environmental stressors and adverse toxicological outcomes. Here, we demonstrate that exposure to noncytotoxic concentrations of AgNPs induces significant genome-wide alterations in DNA hydroxymethylation in mouse embryonic stem cells, which primarily is mediated by TET dioxygenase-dependent pathways. Further investigation shows that AgNPs activate TETs through a reactive oxygen species (ROS)-dependent manner, independent of the Ag⁺ ion. Our findings provide evidence that AgNPs disrupt TET-mediated DNA demethylation and reveal a novel epigenetic mechanism by which nanoparticles perturb DNA methylation homeostasis during early embryonic development.