ABSTRACT: Gestational diabetes mellitus (GDM) is a pregnancy-specific metabolic disorder associated with adverse maternal and fetal outcomes, with epigenetic dysregulation increasingly implicated in fetal programming. As the placenta plays a central role in maternal–fetal nutrient and hormonal exchange, this study investigated structural, epigenetic, and metabolic alterations in placentas from GDM pregnancies. Pregnant women recruited from PRS Hospital Pvt. Ltd. were classified as normoglycemic and GDM based on oral glucose tolerance test results, and maternal blood, cord blood, and placental tissues were collected for histological evaluation, DNA methylation profiling, lipid analysis, and gene expression studies. GDM placentas exhibited pronounced morphological abnormalities, including increased syncytial knots, chorangiosis, villous immaturity, and fibrinoid necrosis. Epigenomic analysis identified 521 differentially methylated regions, with significant enrichment in lipid metabolism pathways; notably, the lipid-associated gene PLIN1 was hypermethylated and significantly downregulated in GDM placentas. Concordantly, lipid profiling of maternal and cord blood revealed marked dyslipidemia in GDM subjects, indicating disrupted lipid homeostasis at both molecular and systemic levels. Collectively, these findings demonstrate that GDM induces coordinated structural, epigenetic, and metabolic alterations in the placenta that may influence fetal lipid exposure and contribute to long-term metabolic risk, highlighting PLIN1 as a potential biomarker and therapeutic target.
