Dorey Emily S, Pantaleon Marie, Weir Kristy A, Moritz Karen M
School of Biomedical SciencesThe University of Queensland, St Lucia, Queensland 4072, Australia.
School of Biomedical SciencesThe University of Queensland, St Lucia, Queensland 4072, Australia
Reproduction. 2014 Jun;147(6):R189-98. doi: 10.1530/REP-13-0478. Epub 2014 Mar 31.
The 'developmental origins of health and disease' hypothesis suggests that many adult-onset diseases can be attributed to altered growth and development during early life. Perturbations during gestation can be detrimental and lead to an increased risk of developing renal, cardiovascular, metabolic, and neurocognitive dysfunction in adulthood. The kidney has emerged as being especially vulnerable to insult at almost any stage of development resulting in a reduction in nephron endowment. In both humans and animal models, a reduction in nephron endowment is strongly associated with an increased risk of hypertension. The focus of this review is twofold: i) to determine the importance of specific periods during development on long-term programing and ii) to examine the effects of maternal perturbations on the developing kidney and how this may program adult-onset disease. Recent evidence has suggested that insults occurring around the time of conception also have the capacity to influence long-term health. Although epigenetic mechanisms are implicated in mediating these outcomes, it is unclear as to how these may impact on kidney development. This presents exciting new challenges and areas for research.
“健康与疾病的发育起源”假说表明，许多成年后发病的疾病可归因于生命早期生长发育的改变。孕期的干扰可能有害，并导致成年后患肾脏、心血管、代谢和神经认知功能障碍的风险增加。肾脏在几乎任何发育阶段都特别容易受到损伤，从而导致肾单位数量减少。在人类和动物模型中，肾单位数量减少与高血压风险增加密切相关。本综述的重点有两个方面：一是确定发育过程中特定时期对长期编程的重要性；二是研究母体干扰对发育中肾脏的影响以及这如何引发成年后发病的疾病。最近的证据表明，受孕前后发生的损伤也有影响长期健康的能力。尽管表观遗传机制与介导这些结果有关，但尚不清楚它们如何影响肾脏发育。这带来了令人兴奋的新挑战和研究领域。
