Transplacental Toxicity of Zinc Oxide Nanoparticles: Maternal-Fetal DNA Damage and Organ Accumulation

Nanomaterials (NMs) offer substantial technological advantages, yet their potential adverse biological effects remain a critical concern. This study investigates the maternal-fetal toxicity of zinc oxide nanoparticles (ZnONPs) following a single intravenous (i.v.) administration in vivo, focusing on oxidative DNA damage, cytotoxicity, and transplacental transfer. The median lethal dose (LD₅₀) of ZnONPs was determined to be 154 mg/kg of body weight. Pregnant rats on gestational day 19 were exposed to two sub-lethal doses (3.09 and 7.71 mg/kg; corresponding to 1/50 and 1/20 of LD50). Subsequent analyses assessed Zn²⁺ accumulation, histopathological alterations in maternal organs, and induction of 8-hydroxydeoxyguanosine (8-OHdG) in maternal and fetal tissues. ZnONPs demonstrated systemic distribution, with pronounced accumulation in the liver, spleen, and placenta, and were shown to cross the placental barrier, leading to fetal exposure. Elevated Zn²⁺ concentrations were positively correlated with cytotoxicity and 8-OHdG induction across maternal and fetal compartments. These findings provide compelling evidence of ZnONPs-mediated cyto- and genotoxicity in both mothers and offspring, underscoring the need to define safety margins and regulatory thresholds for nanomaterial exposure in biomedical and environmental contexts.