Reproductive Toxicology Of Oral Exposure To Zinc Oxide Nanoparticle During Gestation And Mechanism Studies

Zinc oxide nanoparticles(ZnO NPs)are a new type of zinc oxide material.In general,zinc oxide with a dimension of less than 100 nm in three dimensions can be called ZnO NPs.ZnO NPs are widely used in rubber,cosmetics,coatings,catalysts,ceramics,health products and foods.With the wide application of ZnO NPs and large amount of ZnO NPs release in to environment,the probability of ZnO NPs being exposed to the organisms greatly increased through breathing,eat and touch.Its impact on organisms has attracted increasing attention.Existing studies shows that ZnO NPs have strong environmental pollution capacity and have been identified as environmental pollutants in the standards of the Organization for Economic Co-operation and Development.Existing animal toxicology studies shows ZnO NPs can cause maternal injury and cause intrauterine dysplasia and nervous system damage in the offspring.However,the safe dose of ZnO NPs is not clear,the toxicity mechanism also not been fully elucidated.This study reviewed the reproductive toxicity of ZnO NPs and its potential association with endoplasmic reticulum stress,explored the relationship between reproductive toxicity and dose of ZnO NPs during oral exposure and its potential mechanism of molecular toxicity.The protective effects of this two cell stress inhibitors N-Acetyl-cysteine(NAC)and Salubrinal(Sal)on the reproductive toxicity of ZnO NPs and verified the molecular mechanisms mentioned above.The contents of each chapter are described as follows:The first chapter reviews the reproductive toxicity of ZnO NPs,the relationship between nanomaterials and endoplasmic reticulum stress,and the relationship between endoplasmic reticulum stress and reproductive.The second chapter mainly explores the reproductive toxicity of ZnO NPs exposed during pregnancy,and preliminary analysis of its molecular mechanism of toxicity.In this study,the weight of pregnant rats,blood routine,hormone content,zinc content,placental histological analysis and offspring development were evaluated.The experimental results shows that oral exposure to 180 mg/kg and 540 mg/kg of ZnO NPs during pregnancy can cause weight loss and inflammation in pregnant mice.ZnO NPs can accumulate in the reproductive organs,causing damage to the mouse placenta and induce fetal growth restriction and fetal number decrease.After exposure to 540 mg/kg ZnO NPs,the transcription and translation level of key genes in the relevant pathways such as oxidative stress,endoplasmic reticulum stress,apoptosis and cell damage repair in the placenta increased,and the transcription level of placental function-related genes was down-regulated.The third chapter mainly studies the protective effects of cellular oxidative stress inhibitor NAC and endoplasmic reticulum stress inhibitor Sal on reproductive toxicity induced by ZnO NPs,and further explores its intrinsic molecular mechanism.In this study,we evaluated the weight,blood routine,hormone content,zinc content,placental histological change and offspring development of pregnant rats.The results showed that this two kinds of cell stress inhibitors can alleviate the weight loss of pregnant mice;reduce zinc content in the uterus,placenta,fetal;reverse development of the offspring;increase number of fetal after ZnO NPs exposure.In addition,this study analysis transcriptional level of some key gene in placenta.The results shows NAC restored the redox balance in the placenta,inhibited the occurrence of endoplasmic reticulum stress,and alleviated the dysfunction caused by ZnO NPs;Sal inhibits the occurrence of endoplasmic reticulum stress and alleviates the dysfunction caused by ZnO NPs.