Gestational diabetes mellitus changes the DNA methylation profile in cord blood and leads to neonatal immune dysregulation

Abstract Background Gestational diabetes mellitus (GDM) affects the immune balance of pregnant women and their offspring. However, most studies on cord blood have not yielded satisfactory results. Most studies in the field of epigenetics have problems such as small data size, unqualified sampling, cannot be repeated verification, the results are not significant, and usually, there is no multi-omics analysis. Therefore, it is difficult to systematically reveal the critical factors of epigenetic changes in GDM on the immune function of the offspring of GDM pregnant women. Results We randomly recruited 30 pregnant women, including 20 pregnant women with GDM (experimental group) and 10 pregnant women without GDM (control group). 9327 genes in hyper-methylated DMPs, 10908 genes in hypo-methylated DMPs, 42 genes in hyper-methylated DMRs, and 209 genes in hypo-methylated DMRs were identified. Through integration analysis with multiple datasets in the GEO public database, it was found that the genes obtained by DMPs were more accurate than those obtained by DMRs. Through data analysis, we got two groups of gene sets, and functional analysis found that they were related to human immune function. After immune infiltration analysis, it was found that CD4T cells were significantly reduced in the cord blood of pregnant GDM women. To further verify the effect of GDM on cord blood immune function, the integration analysis of the two gene sets identified HIST1H1B and PRTN3 genes. Among them, the cg24587427 and cg00700007 sites of the HIST1H1B gene were significantly correlated with the amount of CD4T cells in the cord blood. Conclusions In this study, we broke the previous lack of practical results from cord blood in terms of epigenetics and confirmed that the changes in the intrauterine environment of pregnant women with GDM affect the immune function of newborns.