DNA Methylation Profiles in Placenta and Its Association with Gestational Diabetes Mellitus

Abstract

Emerging evidences indicate that placenta plays a critical role in gestational diabetes mellitus (GDM). DNA methylation could be associated with altered placental development and functions. This study is to uncover the genome-wide DNA methylation patterns in this disorder. DNA methylation was measured at >385 000 CpG sites using methylated DNA immunoprecipitation (MeDIP) and a huamn CpG island plus promoter microarray. We totally identified 6 641 differentially methylated regions (DMRs) targeting 3 320 genes, of which 2 729 DMRs targeting 1 399 genes, showed significant hypermethylation in GDM relative to the controls, whereas 3 912 DMRs targeting 1 970 genes showed significant hypomethylation. Functional analysis divided these genes into different functional networks, which mainly involved in the pathways of cell growth and death regulation, immune and inflammatory response and nervous system development. In addition, the methylation profiles and expressions of 4 loci (RBP4, GLUT3, Resistin and PPARα) were validated by BSP for their higher log2 ratio and potential functions with energy metabolism. This study demonstrates aberrant patterns of DNA methylation in GDM which may be involved in the pathophysiology of GDM and reflect the fetal development. Future work will assess the potential prognostic and therapeutic value for these findings in GDM.

Key words

DNA methylation - placenta - gestational diabetes mellitus - microarray

^* These authors contributed equally to this work.

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