School of Biomedical Sciences, The University of Queensland, St Lucia 4072, Australia.
Placenta. 2010 Mar;31 Suppl:S40-6. doi: 10.1016/j.placenta.2010.01.006. Epub 2010 Jan 29.
The "Developmental Origins of Health and Disease" hypothesis has caused resurgence of interest in understanding the factors regulating fetal development. A multitude of prenatal perturbations may contribute to the onset of diseases in adulthood including cardiovascular and renal diseases. Using animal models such as maternal glucocorticoid exposure, maternal calorie or protein restriction and uteroplacental insufficiency, studies have identified alterations in kidney development as being a common feature. The formation of a low nephron endowment may result in impaired renal function and in turn may contribute to disease. An interesting feature in many animal models of developmental programming is the disparity between males and females in the timing of onset and severity of disease outcomes. The same prenatal insult does not always affect males and females in the same way or to the same degree. Recently, our studies have focused on changes induced in the kidney of both the fetus and the offspring, following a perturbation during pregnancy. We have shown that changes in the renin-angiotensin system (RAS) occur in the kidney. The changes are often sex specific which may in part explain the observed sex differences in disease outcomes and severity. This review explores the evidence suggesting a critical role for the RAS in sex specific developmental programming of disease with particular reference to the immediate and long term changes in the local RAS within the kidney.
“健康与疾病的发育起源”假说引起了人们对调节胎儿发育的因素的重新关注。许多产前干扰因素可能导致成年后出现心血管和肾脏疾病等疾病。使用动物模型，如母体糖皮质激素暴露、母体卡路里或蛋白质限制和胎盘功能不全，研究已经确定了肾脏发育的改变是一个共同的特征。低肾小球发生可能导致肾功能受损，进而可能导致疾病。在许多发育编程的动物模型中，一个有趣的特征是男性和女性在疾病发病时间和严重程度上存在差异。同样的产前刺激并不总是以相同的方式或相同的程度影响男性和女性。最近，我们的研究集中在怀孕期间受到干扰后，胎儿和后代肾脏中诱导的变化。我们已经表明，肾素-血管紧张素系统 (RAS) 的变化发生在肾脏中。这些变化通常具有性别特异性，这在一定程度上可以解释观察到的疾病结局和严重程度的性别差异。这篇综述探讨了 RAS 在疾病性别特异性发育编程中具有关键作用的证据，特别提到了肾脏内局部 RAS 的即时和长期变化。
