Exploration Of Fetal Brain Accumulation Of ZrO₂ Nanoparticle After Oral Exposure To Pregnant Mice

The wide application of nanomaterials has brought great convenience to our lives,and at the same time it can also enter the human body through various means,posing a potential threat to human health.As a susceptible population,pregnant women exposed to nanomaterials are likely to have an adverse effect on offspring.Because the offspring's various functions,such as the blood-brain barrier,require a developmental process in the pregnant mother.The blood-brain barrier is not fully developed until the 15th day of the embryonic period.Therefore,during pregnancy exposure,especially the barrier is not fully developed,nanomaterials can easily enter the brain of offspring and thus produce harmful biological effects.Our partners use zirconium dioxide nanomaterials to treat wastewater,and duringthis process,zirconium dioxide nanomaterials will inevitably enter the water,so it is necessary to evaluate the water samples treated by zirconium dioxide nanomaterial to ensure their biological safety.Existing studies shows that pregnant mice have not yet exposed to zirconia nanomaterials to study the distribution of nanomaterials in the progeny of the brain before and after the formation of the blood-brain barrier.In this paper,we used the pregnant mice as a model to study the oral exposure of zirconia nanomaterials before and after the formation of the offspring's blood-brain barrier.To study the safe dose range that the mother can bear,we study the maternal tolerable safe dose range,and in this safe dose range,whether nanomaterials can enter the brain of fetus or not.In the first part,first of all,it is necessary for us to confirm the physical characterization of nano-ZrO₂.The crystal form of nano-ZrO₂ is determined by X-ray diffraction.Since nano-ZrO₂ has three different crystal forms,it is necessary to determine that the selected nano-ZrO₂ is a desired crystal form.In addition,the particle size and homogeneity of nanomaterials were understood by transmission electron microscopy and scanning electron microscopy.Furthermore,the hydration particle size of the nano-ZrO₂ is also needed,and different pHs are set to simulate the presence of nanomaterials in gastric juice,body fluids,and intestinal juices,as well as the stability of the nanomaterials in a certain period of time.The nanomaterials can also enter the blood,so we need to add nanomaterials in the fetal bovine serum experiment to explore.It is also necessary to study the potential of nanomaterials at different pH levels and analyze the aggregation of nanomaterials in different environments through potential conditions.However,considering whether there are zirconium elements in normal mice or not,we also measured the content of zirconium in mouse organs and serum of different strains.Through the above experiments,we have laid a good beginning for the next experiment.·In the second part,taking into account the many similarities between the human body and rodents,we used the pregnant mice as a model to carry out experimental exploration of different stages.Firstly,the formation time of the blood-brain barrier was used as the demarcation point,we studied the accumulation of nanomaterials before and after the formation of the blood-brain barrier.Considering the recovery period of pregnant mice exposed to nanomaterials,we killed the mice at once before the formation of the blood-brain barrier.The other two groups of pregnant mice were killed at the same time.Studies have shown that nanomaterials do not enter the brain of offspring before and after the formation of the blood-brain barrier.Next pregnant mice were exposed to nanomaterials in 14 days continuously.We found nanomaterials could across blood-brain barrier and found that nanomaterials could indeed enter the brain.However,nanomaterials was not found in the brain in two days before and after the formation of blood-brain barrier.On the one hand,it may because time is short.Another possibility is that once the blood-brain barrier begins to appear,the blood-brain barrier immediately works.This experiment provides strong guidance for the safety of treated water samples contained nano-ZrO₂.At the same time,the water samples treated with nano-ZrO₂ were also evaluated,we estimate the water concentration of actually exposed nano-ZrO₂ reasonably.