The Effects And Mechanism Of Sodium Arsenite On Preimplantation Embryo Development In Mouse

As the initial form of mammalian life,the fate of pre-implantation embryos is closely related to embryo implantation,pregnancy outcome and the overall physiological status of offspring.During the period before implantation into the uterus,embryos are particularly sensitive to the changes of environmental factors owing to their drastic changes in gene expression,protein synthesis,energy requirements and amino acid metabolism.As a kind of heavy metal salt,sodium arsenite itself is not easy to be degraded.Females are susceptible to arsenic exposure when breeding their offspring.Previous studies showed that sodium arsenite affected the reproductive efficiency of female animals through multiple ways,such as abnormal meiosis of oocytes,abnormal cell differentiation,changes of DNA methylation and abnormal elevation of ROS.However,the specific mechanism by which it hinders the development of pre-implantation embryos is still unclear.In this study,the effect of sodium arsenite on the development of mouse pre-implantation embryos and its mechanism are investigated by using mouse embryo culture system in vitro.The specific research results are as follows:(1)When 1-cell embryos were treated with different concentrations of sodium arsenite(1 μM,3 μM,and 5 μM),sodium arsenite influenced the development of early mouse embryos in a dose-dependent manner.Most embryos(87.09±4.53%)were arrested at 2-cell stage after treated by 5 μM sodium arsenite.(2)Transcriptome analysis of 2-cell embryos treated with 5 μM sodium arsenite revealed that the transcription levels of 3069 genes had changed,including of 1672up-regulated genes and 1397 down-regulated genes.Zygotic genome activation(ZGA)of 2-cell embryo was inhibited.At the same time,the degradation of maternal effect genes was abnormal,and the degradation of zygote-dependent maternal effect genes was most affected.(3)Although sodium arsenite did not alter the distribution of H3K27 ac modification in 2-cell embryos,it reduced the genome-wide enrichment level of H3K27 ac in the whole genome wide.Sodium arsenite reduced the modification level of H3K27 ac in the BRG1 promoter region,and the transcription of the gene itself was inhibited,which in turn affected embryonic development.