Toxic Effects Of Maternal Cadmium Exposure On The Metabolism And Transport System Of Amino Acids In The Maternal Livers

Cadmium is a common environmental pollutant,which can induce fetal malformation and intrauterine growth restriction.However,the molecular mechanism of intrauterine growth restriction caused by maternal cadmium exposure during pregnancy is still unclear,and there are obvious deficiencies in the study of the toxic effects of metabolic and transport functions of nutrients in the liver of pregnant rats after cadmium exposure.Therefore,based on the previously established mouse model of maternal cadmium exposure during pregnancy,we detected the contents of certain nutrients in serum and fetal liver of mice by biochemical methods to analyze the effects of cadmium exposure on maternal nutritional supply function.To elucidate the regulatory mechanism of maternal nutrient content changes,we examined the expression levels of several key genes related to nutrient absorption and transport in the maternal liver of mice by real-time quantitative PCR and Western blotting,and detected the metabolic reactions and related pathways in the maternal liver by gas chromatography-time of flight-mass spectrometry(GC-TOFMS).In addition,the changes of liver function and tissue structure after cadmium exposure were also examined by biochemical and HE staining methods.The results showed that,compared with the control group,maternal cadmium exposure during pregnancy resulted in a significant decrease in fetal weight at the end of pregnancy(E19.5),but had no significant effect on the number of fetal pups and maternal liver weight.The levels of total amino acids in serum and fetal liver of cadmium exposed mice decreased significantly.The expression levels of three amino acid transporter genes(SNAT4,SNAT7 and ASCT1)in maternal liver of cadmium-exposed mice were upregulated.The results of GC-TOF-MS analysis showed that the expression levels of several amino acids and their derivatives were also increased.Further bioinformatics analysis showed that the metabolic pathways mainly affected by cadmium exposure included the metabolism of alanine,aspartic acid and glutamic acid,the biosynthesis of valine,leucine and isoleucine,and the metabolism of arginine and proline.In addition,cadmium exposure also caused liver dysfunction and histopathological changes in pregnant mice.The following conclusions are drawn :(1)Maternal cadmium exposure during pregnancy leads to an abnormal increase in the expression level of amino acid transporters in maternal liver,and the amino acid supply function in maternal blood is insufficient;(2)Maternal cadmium exposure during pregnancy resulted in abnormal activation of multiple amino acid metabolic pathways in maternal liver;(3)Maternal cadmium exposure during pregnancy may induce a large amount of amino acids in maternal blood to be absorbed by the liver,causing a lack of maternal nutrition supply(amino acids),and ultimately leading to fetal growth restriction.