Introduction and Objective: Intrauterine exposure to Type 2 Diabetes Mellitus (T2DM) has been associated with an increased risk of cardio-metabolic disorders in offspring, potentially driven by epigenetic modifications primarily DNA methylation. This study aims to investigate the DNA methylation profiles of placental tissues from women with T2DM pregnancies compared to those from normoglycemic (NG) pregnancies.Methods: Subjects were classified as T2DM (HbA1c >6.5%, n=25) or NG (HbA1c < 5.8%, n=50) and matched for age, Body Mass Index(BMI), and blood pressure. Exclusion criteria included systemic chronic diseases such as coronary artery disease, asthma, familial hypercholesterolemia, hypertension, and preeclampsia. Placental DNA was isolated from NG(n=6) and T2DM (n=5) samples. Bisulfite conversion and methylation profiling were performed using Illumina’s 850K Infinium methylation EPIC BeadChip array. Differential Methylation was performed using the GenomeStudio Differential Methylation Analysis module on the overall CpG sites. Significant genes were identified based on DiffScore (>13 /<-13) and Delta Beta (>0.2 /<-0.2). Gene Ontology (GO) analysis for significant CpG regions was performed using DAVID database.Results: DNA methylation analysis revealed differentially methylated CpG sites between T2DM and NG groups. Gene ontology (GO) analysis of these sites identified pathways associated with diabetes, cardiovascular diseases, obesity and metabolic syndrome.Conclusion: In utero exposure to Type 2 Diabetes Mellitus (T2DM) is associated with DNA methylation alterations in the placenta reflecting adaptive responses to glucose intolerance which may potentially influence long-term health of the offspring.
A. S: None. A. Jaleel: None. S. Ramachandran: None.
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