Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Agro Paris Tech, Université Paris-Saclay, Paris, France.
Am J Physiol Renal Physiol. 2024 Jul 1;327(1):F21-F36. doi: 10.1152/ajprenal.00383.2023. Epub 2024 May 2.
According to the Developmental Origins of Health and Disease hypothesis, exposure to certain environmental influences during early life may be a key determinant of fetal development and short- and long-term offspring health. Indeed, adverse conditions encountered during the fetal, perinatal, and early childhood stages can alter normal development and growth, as well as put the offspring at elevated risk of developing long-term health conditions in adulthood, including chronic kidney disease and cardiovascular diseases. Of relevance in understanding the mechanistic basis of these long-term health conditions are previous findings showing low glomerular number in human intrauterine growth restriction and low birth weight-indicators of a suboptimal intrauterine environment. In different animal models, the main suboptimal intrauterine conditions studied relate to maternal dietary manipulations, poor micronutrient intake, prenatal ethanol exposure, maternal diabetes, glucocorticoid and chemical exposure, hypoxia, and placental insufficiency. These studies have demonstrated changes in kidney structure, glomerular endowment, and expression of key genes and signaling pathways controlling endocrine, excretion, and filtration function of the offspring. This review aims to summarize those studies to uncover the effects and mechanisms by which adverse gestational environments impact offspring renal and vascular health in adulthood. This is important for identifying agents and interventions that can prevent and mitigate the long-term consequences of an adverse intrauterine environment on the subsequent generation. Human data and experimental animal data show that suboptimal environments during fetal development increase the risk of renal and vascular diseases in adult-life. This is related to permanent changes in kidney structure, function, and expression of genes and signaling pathways controlling filtration, excretion, and endocrine function. Uncovering the mechanisms by which offspring renal development and function is impacted is important for identifying ways to mitigate the development of diseases that strain health care services worldwide.
根据健康与疾病的发育起源假说，生命早期暴露于某些环境影响可能是胎儿发育以及短期和长期后代健康的关键决定因素。事实上，在胎儿、围产期和儿童早期阶段遇到的不良条件可能会改变正常的发育和生长，并使后代在成年后罹患长期健康状况（包括慢性肾脏病和心血管疾病）的风险增加。在理解这些长期健康状况的机制基础方面，先前的研究结果具有重要意义，这些研究结果表明宫内生长受限和低出生体重的人类存在肾小球数量减少，这是宫内环境不佳的指标。在不同的动物模型中，研究的主要宫内不良条件与母体饮食操作、微量营养素摄入不良、产前乙醇暴露、母体糖尿病、糖皮质激素和化学物质暴露、缺氧以及胎盘功能不全有关。这些研究表明，肾脏结构、肾小球发生和控制后代内分泌、排泄和过滤功能的关键基因和信号通路的表达发生了变化。本综述旨在总结这些研究，以揭示不良妊娠环境对后代成年期肾脏和血管健康的影响和机制。这对于确定可以预防和减轻不良宫内环境对后代的长期影响的药物和干预措施非常重要。人类数据和实验动物数据表明，胎儿发育过程中的不良环境会增加成年期肾脏和血管疾病的风险。这与控制过滤、排泄和内分泌功能的基因和信号通路的肾脏结构、功能和表达的永久性变化有关。揭示后代肾脏发育和功能受影响的机制对于确定减轻全球卫生保健服务负担的疾病发展的方法非常重要。
