The Toxic Effect Of Nano-cerium Oxide On Pregnant Rats And Its Mechanism

Part I General toxicology studies of pregnant mice exposure to nano and bulk CeO2 particleIn the toxicology evaluation of chemicals,the most basic and important is the general toxicity evaluation.Safety evaluation of nanomaterials is no exception,first of all,we must analyze and discuss the general toxicological characteristics.At present,there are few comprehensive and systematic studies on the general toxicology of nano cerium oxide in pregnancy.In order to further understanding of the toxicity of repeated exposure nano cerium oxide particles,we refer to an article published in Nature Nanotechnology and designed a subacute toxicity experiments involving in a pregnant mice by tail vein injection of CeO2 NPs 2 day and CeO2 BPs as reference compounds.We investigate toxicity rules of CeO2NPs repeated exposure through conventional indicators(weight,organ coefficient,food intake,water intake),pregnancy-related indicators,and major organ tissue pathological examination.The results showed that gestational exposure to nano and micron cerium oxide,the weight of the mice did not decline,organ coefficient and the amount of food and water have not changed.We determined organism of cerium distribution by ICP/MS.Besides muscle and fat,various organs have accumulated cerium.The results showed that the distribution of cerium element did not complete the size dependent effect,but the element content of the majority of organ exposed to nano cerium was high.Nano cerium oxide particles can be clearly observed in placenta,fetal liver and fetal brain with TEM.Combining with ICP/MS result,we can explain that nano cerium oxide can pass through blood-embryo barrier.Pathological results showed liver cells of cerium oxide exposed group were mild swelling.The renal tubular epithelial cells of CeO2 NPs exposed group were degenerated.Placental labyrinth and decidua zone of CeO2 NPs exposed group has a small amount of thrombus and.Placenta decidual zone of CeO2 BPs appeared obvious thrombus.Pregnancy related indicators showed that live birth,stillbirth,fetal absorption composition proportion of CeO2 NPs and CeO2 BPs did not differ,as well as the ratio of male and female fetuses.Meanwhile,we found that nano-cerium oxide and cerium oxide affects both fetal weight and placental weight.Part II Metabolomics reveals metabolic changes in cerium oxide nanoparticles treated pregnancy miceIncreasing applications of nanoparticles have attracted significant attention to their impacts on human health in recent years.The effects of nanoparticles on pregnancy,however,remain unclear.In this study,we investigated the metabolic impact of the widely used Ce02 nanoparticles(Ce02 NPs)on pregnant ICR mice using the metabolomics technology.We demonstrate that Ce02 NPs and bulk particles(BPs)have distinct influences on serum metabolic profiles and fetal growth in pregnant mice.CeO2 NPs exhibit a reduced ability to disrupt beta-oxidation of very long chain fatty acid,pyrimidine metabolism,tricarboxylic acid(TCA)cycle,and N-a-acetyl-L-lysine and N-acetyl-L-phenylalanine metabolism compared to CeO2 BPs.Consistently,the expression of genes involved in fatty acid oxidation in liver is less induced by CeO2 NPs than by Ce02 BPs.Consequently,Ce02 NPs are less able to restrict fetal growth compared to CeO2 BPs.On the other hand,CeO2 NPs specifically alter the levels of several other metabolites including L-tryptophan,glucose 6-phosphate and L-phenylalanine.Our study provides novel insights into the effects of Ce02 NPs on metabolism in the pregnant mice,and indicates that Ce02 NPs are safer materials for pregnancy than Ce02 BPs.Our finding further suggest that metabolomics is a promising highly sensitive tool for the safety assessment of nanoparticles.