Study On The Expression And Regulatory Mechanism Of Imprinted Genes In The Placenta Of Mice Exposed To Maternal Cadmium During Pregnancy

Cadmium is a kind of toxic environmental pollutants.Cadmium can not only disrupt the body’s metabolism,but also has strong reproductive toxicity.A series of epidemiological studies have confirmed that maternal cadmium exposure is closely related to the occurrence of fetal growth restriction.However,the underlying molecular mechanism of cadmium-induced fetal growth restriction is still unclear.Placenta is the main target organ of fetal growth restriction induced by cadmium.Exploring the abnormally expressed functional genes in the placenta exposed to cadmium may be one of the effective ways to explore the molecular mechanism of cadmium-induced fetal growth restriction.The placenta is an organ with high expression of imprinted genes,and many imprinted genes have been confirmed to be involved in the regulation of the development of the fetus and placenta.Therefore,we build on the established mouse model of fetal growth restriction induced by maternal cadmium exposure during pregnancy.In this study,six imprinted genes(Slc38a4,H19,Grb10,Cdkn1 c,IGF2R and Phlda2)and 7 imprinted genes related to mouse placenta development(Peg10,Gpc3,Chm,Sgce,Plagl1,Dlk1,and Esx1),the expression levels of these imprinted genes in the placentas of each group of mice were then measured(by real-time fluorescent quantitative PCR and Western blot).In addition,We also tested the DNA methylation level of the promoter regions of the differentially expressed imprinted genes(Cdkn1c and Peg10)in the placenta exposed to low-dose cadmium during pregnancy.The experimental results showed that: Firstly,at 19.5 days of pregnancy(Embryonic,E),the expression level of placental imprinted gene Cdkn1 c in the 40 mg/L cadmium exposure group was significantly higher than that of the control group,and there was no significant difference at E16.5 days.Secondly,At E16.5 days and E19.5 days,the expression level of placental imprinted gene Peg10 in the 40 mg/L cadmium exposure group was significantly lower than that of the control group.Secondly,compared with the control group,the DNA methylation level at position 2 of the promoter region of the imprinted gene Cdkn1 c in the mouse placenta treated with different concentrations of cadmium was significantly lower at E16.5 days,and the DNA methylation at position 1compared with the control group,there was no significant change in the level;the DNA methylation level of the gene promoter region of the imprinted gene Peg10 in the mouse placenta of the different concentration of cadmium treatment group was significantly higher at E16.5 days compared with the control group.Conclusion based on the above results:Firstly,fetal growth restriction induced by maternal cadmium exposure during pregnancy may be related to the imbalance of expression levels of Cdkn1 c and Peg10 imprinted genes in mouse placenta.Secondly,the differentially expressed genes Cdkn1 c and Peg10 in placenta of mice exposed to maternal cadmium during pregnancy may be related to DNA methylation modification in the promoter region.