DNA Methylation Profiles in Diabetic Embryos

Maternal diabetes is a known factor for neural tube defects (NTDs) in offspring. DNA methylation could be associated with NTDs induced by maternal diabetes. This study investigated whether maternal diabetes disturbs embryonic DNA methylation, with a focus on genes involved in neural tube closure. Our study showed that the overall distribution of DNA methylation was not significantly different between nondiabetic and diabetic embryos. However, further analysis showed that the methylation levels of differentially methylated CpGs (dmCpGs) around transcription start sites, gene body, and transcription end sites were higher in nondiabetic embryos than in diabetic embryos. There was an increased methylation level of dmCpGs in CpG islands in diabetic embryos compared to that of nondiabetic embryos. Meanwhile, maternal diabetes significantly resulted in differential methylation of CpG islands in the promoter and gene body region of genes such as Sphingosine kinase-1 (Sphk1), twist basic helix-loop-helix transcription factor 1 (Twist1), and shroom family member 3 (Shroom3), and the gene expression of these genes was altered by maternal diabetes. This study suggested that changes in DNA methylation in diabetic embryos may be involved in the pathophysiology of NTDs induced by maternal diabetes through aberrant expression of genes.