Placental Delta-Like 1 Gene DNA Methylation Levels Are Related to Mothers' Blood Glucose Concentration

We aim to identify the methylation status of delta-like 1 (DLK1) in the placenta and the correlation between DLK1 methylation and maternal serum glucose level and fetal birth weight.

We analyzed the gene expression of DLK1 gene in both maternal and fetal sides of the placenta in a GDM group (n = 15) and a control group (n = 15) using real-time polymerase chain reaction. With MethylTargetTM technique, we detected the methylation status of DLK1 promotor in the placenta. Furthermore, Pearson's correlation was used to confirm the association of methylation alteration of DLK1 promoter and maternal 2 h OGTT glucose level and fetal birth weight.

In our study, we found that DLK1 expression in both maternal and fetal sides of the placenta decreased significantly in GDM group compared with control group, and it was caused by hypermethylation of DLK1 promoter region. Additionally, the methylation status of DLK1 gene in the maternal side of the placenta highly correlated with maternal 2 h OGTT glucose level (coefficient = 0.7968, P < 0.0001), while the methylation status in the fetal side of the placenta was closely related to fetal birth weight (coefficient = 0.6233, P < 0.0001).

Our results demonstrated that altered expression of DLK1 was caused by the hypermethylation of DLK1 promoter region in the placenta, and intrauterine exposure to GDM has long-lasting effects on the epigenome of the offspring.