Tortelote Giovane G
Section of Pediatric Nephrology, Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
Curr Diab Rep. 2024 Dec 18;25(1):13. doi: 10.1007/s11892-024-01569-9.
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.
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. 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.
本综述探讨妊娠期糖尿病(GDM)影响胎儿肾脏发育的机制,重点关注表观遗传改变作为这些影响的介导因素。我们研究了GDM对肾发生和肾脏成熟的影响,探讨高血糖诱导的宫内应激如何通过正常表观遗传机制的失调减少肾单位数量并损害肾功能。
除代谢影响外,新出现的证据表明GDM通过表观遗传修饰发挥作用,包括DNA甲基化、组蛋白修饰和非编码RNA表达,这些修饰会破坏对肾脏发育至关重要的基因表达模式。最近,在暴露于GDM的后代中观察到的特定表观遗传修饰与肾脏发育必需基因的异常激活或抑制有关。讨论了受这些表观遗传变化影响的关键途径,如氧化应激反应、炎症调节和代谢途径,以说明GDM对肾脏发育的广泛分子影响。最后,我们考虑了可能减轻GDM对肾脏发育不利影响的潜在干预策略。这些策略包括优化母体血糖控制、饮食调整、膳食补充以及针对表观遗传途径的药物。通过对当前研究的全面综合,本综述强调了早期预防策略对于减轻暴露于GDM个体的肾脏疾病负担的重要性,并突出了GDM期间影响肾脏发育的关键表观遗传机制。