Neurodevelopmental toxicity induced by iron oxide nanoparticles: Insights from chick and zebrafish embryonic models.

Iron oxide nanoparticles (IONPs) are widely applied in biomedicine and industry, yet their impact on early nervous system formation is poorly understood. Here, we assessed IONP toxicity using cultured chick embryo fibroblasts, fertilized chicken eggs, and zebrafish embryos. In vitro exposure reduced fibroblast viability, elevated lipid peroxidation, and boosted reactive oxygen species levels. The injection of IONPs in chick embryo caused growth delays, smaller brain size, neuroepithelial thickening, and marked loss of neural stem and progenitor cells. At the molecular level, IONPs reduced PI3K and mTOR activity, increased apoptotic markers, and induced ferroptosis hallmarks, including mitochondrial membrane potential loss, ATP depletion, elevated mitochondrial ROS, and downregulation of xCT and GPX4. In zebrafish, IONPs triggered early developmental defects, microcephaly, and yolk malabsorption, alongside redox imbalance and dysregulation of ferroptosis-related genes. Together, these data show that IONPs impair neural proliferation, promote multiple forms of cell death, and disrupt redox equilibrium through ferroptotic mechanisms, highlighting the need for careful safety evaluation before their widespread use.