The Impact of Gestational Diabetes on Kidney Development: is There an Epigenetic Link?

Abstract

Purpose of Review This review explores the mechanisms through which gestational diabetes mellitus GDM impacts fetal kidney development, focusing on epigenetic alterations as mediators of these effects. We examine the influence of GDM on nephrogenesis and kidney maturation, exploring how hyperglycemia-induced intrauterine stress can reduce nephron endowment and compromise renal function via dysregulation of normal epigenetic mechanisms. Recent Findings In addition to metabolic impacts, emerging evidence suggests that GDM exerts its influence through epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNA expression, which disrupt gene expression patterns critical for kidney development. Recently, specific epigenetic modifications observed in offspring exposed to GDM were implicated in aberrant activation or repression of genes essential for kidney development. Key pathways influenced by these epigenetic changes, such as oxidative stress response, inflammatory regulation, and metabolic pathways, are discussed to illustrate the broad molecular impact of GDM on renal development. Finally, we consider potential intervention strategies that could mitigate the adverse effects of GDM on kidney development. These include optimizing maternal glycemic control, dietary modifications, dietary supplementation, and pharmacological agents targeting epigenetic pathways. Summary Through a comprehensive synthesis of current research, this review underscores the importance of early preventive strategies to reduce the burden of kidney disease in individuals exposed to GDM and highlights key epigenetic mechanisms altered during GDM that impact kidney development.