| Zinc oxide nanoparticles(ZnO NPs)as one of the most common used new nanomaterials,because of their unique optical,chemical,electrical and biological properties,as well as good antibacterial properties,are widely used in Medical equipment and health care,food additives and food packaging and other fields.With the wide application and mass emission of ZnO NPs,the probability of ZnO NPs being exposed to the body through breathing,oral cavity and skin is also greatly increased.Therefore,the biosafety of ZnO NPs has attracted more and more attention from the industry.Existing studies have shown that ZnO NPs has a relatively strong environmental pollution capacity and has been characterized as an environmental pollutant in the standards of the Organization for Economic Co-operation and Development.Existing animal toxicology studies show that ZnO NPs enter the body and accumulate in the ovary,affecting ovarian function and causing reproductive toxicity.However,the safe dose to which this material is exposed is unknown,and the mechanism of toxicity is not fully elucidated.This study reviewed the effects of ZnO NPs on ovarian function and the endoplasmic reticulum,explored the dose-effect relationship of ZnO NPs on ovarian function and its potential toxic molecular mechanism,and subsequently explored cellular stress The protective effect of tunicamycin(TM)on the destruction of ovarian function by ZnO NPs,and the above molecular mechanism was verified.Secondly,the dose-response relationship of subacute oral exposure of ZnO NPs to ovarian function and its potential molecular mechanism of toxicity were explored.The contents of each chapter are as follows:The first chapter discusses the effects of nanomaterials on ovarian function and the relationship between endoplasmic reticulum stress and ovarian function.The second chapter mainly explores the effects of acute(1 d and 7 d)oral exposure of ZnO NPs on ovarian function and preliminary analysis of its molecular mechanism of toxicity.This study carried out a compr-ehensive evaluation of mouse weight,ovarian organ coefficient,serum neutral hormone content,zinc content,and ovarian pathological damage.The experimental results show that acute oral exposure to ZnO NPs,high doses of ZnO NPs can inhibit the growth of mice and cause abnormal ovarian organ coefficients.At the same time,medium and high doses of ZnO NPs(200,400 mg/kg)will accumulate in the ovaries,destroy the ovarian structure and increase the number of follicular occlusions,and the vacuolation of follicles.Intraovary after exposure to medium and high doses of ZnO NPs Endoplasmic reticulum stress related genes and hormone synthesis related genes were significantly down-regulated.There were no significant changes in serum sex hormones(estradiol and progesterone).The third chapter mainly studies the protective effect of endoplasmic reticulum stress activator TM on the destruction of ovarian function by ZnO NPs,and further explores its intrinsic molecular mechanism.This study performed a comprehensive evaluation of mouse body weight,ovarian organ coefficient,hormone content,zinc content,and ovarian pathological damage.Experimental results show that endoplasmic reticulum stress activators can alleviate the weight loss of mice caused by ZnO NPs,accumulation of zinc content in the ovary,and pathological changes in the ovary.In addition,this study performed a transcriptional analysis of the ovaries of each group of mice.The results showed that TM supplementation restored endoplasmic reticulum stress in the ovaries and restored the expression of hormone synthesis genes.The fourth chapter mainly explores the effects of subacute(28 d)oral exposure of ZnO NPs on ovarian function and preliminary analysis of its molecular mechanism of toxicity.This study carried out a comprehensi-ve evaluation of mouse weight,ovarian organ coefficient,serum neutral hormone content,zinc content,ovarian pathological damage,and estrous cycle.The experimental results show that subacute oral exposure to ZnO NPs and high doses of ZnO NPs 560 mg/kg)can inhibit the growth of mice and cause abnormal ovarian organ coefficients.At the same time,ZnO NPs will accumulate in the ovary,destroy the structure of the ovary,increase follicular occlusion,and follicular vacuole.Transcription results showed that there were no significant changes in ER stress-related genes,while ER stress-related downstream apoptosis-related genes increased significantly,while ovarian follicular development and hormone synthesis-related genes were significantly suppressed.There was no significant change in serum sex hormones.The estrous cycle of mice is disordered,and long-term exposure to ZnO NPs increases the number of abnormal estrous cycles of mice. |
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