School of Biomedical Sciences, The University of Queensland, St Lucia, 4067, Australia.
Pediatr Nephrol. 2012 Dec;27(12):2175-82. doi: 10.1007/s00467-012-2108-x.
Maternal perturbations or sub-optimal conditions during development are now recognized as contributing to the onset of many diseases manifesting in adulthood. This "developmental programming" of disease has been explored using animal models allowing insights into the potential mechanisms involved. Impaired renal development, resulting in a low nephron number, has been identified as a common outcome that is likely to contribute to the development of hypertension in the offspring as adults. Changes in other organs and systems, including the heart and the hypothalamic–pituitary–adrenal axis, have also been found. Evidence has recently emerged suggesting that epigenetic changes may occur as a result of developmental programming and result in permanent changes in the expression patterns of particular genes. Such epigenetic modifications may be responsible not only for an increased susceptibility to disease for an individual, but indirectly for the establishment of a disease state in a subsequent generation. Further research in this field, particularly examination as to whether epigenetic changes to genes affecting kidney development do occur, are essential to understanding the underlying mechanisms of developmental programming of disease.
现在人们已经认识到,母体在发育过程中受到干扰或处于亚最佳状态,会导致许多成年后才显现的疾病的发生。通过使用动物模型来探索这种“疾病发育编程”,可以深入了解潜在的相关机制。人们已经发现,肾脏发育受损导致的肾小球数量减少是一种常见的后果,这可能导致后代成年后患高血压。其他器官和系统(包括心脏和下丘脑-垂体-肾上腺轴)的变化也已被发现。最近有证据表明,由于发育编程,表观遗传变化可能会发生,并导致特定基因表达模式的永久性变化。这种表观遗传修饰不仅可能导致个体对疾病的易感性增加,而且还可能间接地导致后代疾病状态的建立。该领域的进一步研究,特别是对影响肾脏发育的基因的表观遗传变化是否确实发生的研究,对于理解疾病发育编程的潜在机制至关重要。