Placental DNA methylation changes in the development of gestational diabetes mellitus

Aims: The aim of this study was to investigate the association between gene methylation alterations and the development of GDM, as well as to investigate the potential epigenetic mechanisms of GDM. Methods Reduced representation bisulfite sequencing (RRBS) and RNA sequencing (RNA-seq) analysis were performed on placental tissues from women with GDM and healthy controls. After pyrosequencing, correlation and linear regression analysis were applied based on the effect of methylated-differentially expressed genes (DEGs). Results HOXD9, ALDH1A2, CSMD1, TRIM67 , and PAX8 , five candidate DEGs, were identified. TRIM67 exhibited significant hypermethylation levels at different CpG sites. Hypermethylation of TRIM67 promoter was significantly positively correlated with 1h and 2h OGTT glucose levels and negatively correlated with Lipoprotein(a). Conclusions TRIM67 hypermethylation in the placenta of women with GDM may correlate with insulin resistance, which may play a role in the development of GDM. These findings provide new insights for further studies on the pathophysiology of GDM.