| Objective: Nano silver(Ag NPs),as one of the engineering nanomaterials widely used in industrial,consumer and biomedical applications,is widely used in electronic products and medical supplies.However,with the development of nanotechnology,the potential risks of direct or indirect human exposure to Ag NPs are increasing.Therefore,the uncertainty of the safe use of Ag NPs is considered to be the main obstacle to the innovation and widely application of nanotechnology.The purpose of this study is to use ICR mice as a model to explore the toxic effects of low,medium and high doses of Ag NPs on the embryonic development and placenta of pregnant mice as well as the mother’s own body,and provide experimental evidence for evaluating the safety of Ag NPs.Method:In this experiment,we used nano-silver powder with a particle size of 20 nm to study the toxicity of maternal pregnancy induced by exposure during pregnancy to 8-week-old ICR pregnant mice by gavage at concentrations of 25,50,and 100 mg/kg,as well as toxic effects of nextgeneration embryos and placentas.After sampling,perform pathological examination on the placenta of the mother mouse,analyze whether the placenta has lesions,analyze the content of IL-6,TNF-α and other inflammatory factors in the plasma and serum of the mother mouse,and analyze the tissues and organs of the mother mouse’s liver,heart,kidney and ovary.As well as the content and location of Ag NPs in placenta and fetal mice,and use scanning electron microscope to characterize the physical and chemical properties of Ag NPs,and analyze their particle size and degree of dispersion.Result:(1)ICP-MS data shows that the biological distribution of all nanosilver treatment groups in maternal tissues is highest in maternal liver,followed by maternal kidney,and embryos have the lowest concentration of silver.(2)The results of blood analysis showed that: compared with the control group,the serum total protein and albumin in the medium and highdose treatment group were significantly decreased,but there was no significant difference in the low-dose treatment group;and the LDH in the low,medium and high-dose treatment groups were increased in varying degrees,but only the LDH in the high-dose group was significantly increased compared with the control group.In addition,the levels of inflammatory factors in maternal serum of medium dose treatment group and high dose treatment group were significantly higher than those of control group by ELISA.The levels of TNF-α,IL-1 β,IL-6 and IL-8 were significantly higher than those of the control group,while the level of IL-10 was significantly lower than that of the control group.In addition,the levels of TNF-α,IL-1 β,IL-6 and IL-8 in the high-dose treatment group were significantly different from those in the medium dose treatment group,and the level of IL-10 was also significantly lower than that in the medium dose treatment group.(3)With the increase of the concentration of nano silver,the SOD activity of placenta in the medium dose group and the high dose group decreased significantly;the low dose group also showed a downward trend,but there was no significant difference compared with the control group;with the increase of the concentration of nano silver,the GSH PX activity of placenta showed a dose-dependent downward trend,and the decrease of low and medium concentration treatment reached a significant level The activities of cat and GSH in placenta decreased with the increase of exposure dose,but only the high concentration group reached significant level.In addition,the content of MDA in placenta tended to increase,but only in the high dose group,the level of MDA increased significantly.In general,nano silver has a dose-dependent effect on antioxidant enzymes and non enzyme substances(SOD,GSH-Px,cat,GSH and MDA)of placenta.(4)The MDA/GSH-Px ratio of the placenta in the3 nano-silver treatment groups all showed a significant upward trend,and the increase in the MDA/GSH-Px ratio also showed a significant dose-dependent effect.(5)According to the quantitative classification statistics of the placenta of the low,medium and high nano-silver treatment groups,the degree of placenta damage in the medium and high dose groups was significantly higher than that of the control group.These data indicate that nano-silver exposure can damage the development and function of the placenta,and placental abnormalities may be the cause of adverse pregnancy outcomes after nanosilver exposure.(6)Compared with the control group,after different doses of nanosilver treatment,the positive cell rate of Bax showed an upward trend,and the increase of medium and high dose treatment reached a significant level;the positive cell rate of Bcl-2 showed a decrease The decline of medium and high-dose treatments has reached a significant level.With the increase of the exposure dose of nanosilver,the ratio of Bax/Bcl-2 also showed an upward trend.Compared with the control group,the ratio of Bax/Bcl-2 at medium and high doses reached a significant level.In addition,compared with the control group,after different doses of nanosilver treatment,the rate of HO-1 positive cells showed a downward trend,and the decrease in medium and high dose treatments reached a significant level.Conclusion:(1)The biodistribution of nano silver treatment group in maternal and embryonic tissues showed that the highest concentration of nano silver treatment group was maternal liver,followed by maternal kidney and placenta,and the lowest concentration of silver in embryo.It is proved that intragastric administration of silver nanoparticles can lead to the accumulation of silver nanoparticles in placenta and fetal tissues,and may lead to adverse pregnancy outcomes.(2)The study of blood inflammatory factors in pregnant rats exposed to nano silver shows that TNF-α is considered to be the key cytokine of placental inflammation.TNF-α,IL-6,IL-8 and IL-1 β can promote the inflammatory response,but IL-10 can play an anti-inflammatory role.(3)The study of biomarkers of oxidative stress in pregnant rat placenta induced by nano silver exposure showed that there were differences in the oxidative stress response intensity of placenta to different doses of nano silver.The ratio of SOD / MDA and MDA / GSH PX were the key indicators to reflect the antioxidant capacity of placenta,and they could more objectively reflect the oxidative damage degree of placenta than a single indicator.(4)The research results of pathological damage and apoptosis of placenta induced by nano silver exposure showed that the damage degree of placenta in medium and high nano silver treatment groups was significantly higher than that in the control group,suggesting that nano silver exposure would damage the development and function of placenta,and the abnormal placenta may be the cause of adverse pregnancy outcome after nano silver exposure.5.The appearance color of uterus of mice treated with nano silver became darker,which caused uterine bleeding and serious uneven embryonic development.Especially,the fetal absorption rate of high-dose group was significantly higher than that of the control group.The number of fetuses was less and the weight of fetuses was lighter,which suggested that nano silver exposure during pregnancy led to adverse pregnancy outcomes. |
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