Oral exposure of pregnant rats to copper nanoparticles caused nutritional imbalance and liver dysfunction in fetus

Copper nanoparticles (Cu NPs) are increasingly used as an animal feed additive in China. In previous studies, it was determined that Cu NPs can penetrate the placental barrier, however, its toxic effects on the fetus have not yet been elucidated. Therefore, in this study, we investigated the potential fetal toxic effects of Cu NPs. Cu NPs were orally administered to pregnant Sprague-Dawley rats from gestation days (GDs) 3-18 at a dose of 60, 120, and 180 mg/kg/day. Cesarean sections were conducted on GD 19. During fetal examination, no toxicities were observed regarding general clinical signs, however, Cu NPs significantly decreased fetal body weight, body length, and liver weights. Cu ions and Cu MPs exhibited similar effects on the fetal development. Cu NPs increased the liver concentration of Cu, and decreased protein levels and Fe in fetuses. Cu NPs also increased oxidative stress and inflammation in the fetus after pregnant rats were exposed to high doses of Cu NPs. Oral exposure to Cu NPs during pregnancy increased Cu concentrations in the fetus, which not only affected fetal development, but also significantly induced oxidative stress and inflammatory responses in fetal liver. Taken together, these findings are valuable to evaluate fetal risk assessment after oral exposure of Cu NPs during pregnancy. Additional comprehensive toxicity studies are deemed necessary to clarify the underlying mechanisms involved.