Budge Helen, Stephenson Terence, Symonds Michael E
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, UK.
Curr Drug Targets. 2007 Aug;8(8):888-93. doi: 10.2174/138945007781386839.
An increase in fetal glucocorticoid exposure has long been considered to be a primary mechanism by which maternal nutritional manipulation may result in long term adaptations in the fetus such that it is at increased risk of a range of adult diseases including hypertension, diabetes and obesity. Animal studies in which high doses of synthetic glucocorticoids have been administered to the mother shown some long term programming effects, but these are nearly always accompanied by a reduction in maternal food intake. In this review, we will, therefore, consider the extent to which maternal food restriction and elevated maternal glucocorticoid concentrations can result in the same or different adaptations within the fetus such that they exhibit developmental changes in blood pressure control and/or metabolic homeostasis. One factor that appears to be critical in determining the mother's response is the stage of gestation at which her nutrient intake is manipulated. This may be explained in part by the placenta's ability to inactivate glucocorticoids. Irrespective of the mechanisms involved, it is clear that long term tissue specific adaptations within a range of organs, including adipose tissue and the kidney, can be greatly altered following changes in maternal glucocorticoid secretion.
长期以来，胎儿糖皮质激素暴露增加一直被认为是母体营养调控可能导致胎儿长期适应性变化的主要机制，从而使胎儿患包括高血压、糖尿病和肥胖症在内的一系列成人疾病的风险增加。对母亲施用高剂量合成糖皮质激素的动物研究显示出一些长期的编程效应，但这些效应几乎总是伴随着母体食物摄入量的减少。因此，在本综述中，我们将探讨母体食物限制和母体糖皮质激素浓度升高在多大程度上会导致胎儿出现相同或不同的适应性变化，从而使其在血压控制和/或代谢稳态方面表现出发育变化。在决定母亲反应方面似乎至关重要的一个因素是对其营养摄入进行调控时的妊娠阶段。这部分可以通过胎盘使糖皮质激素失活的能力来解释。无论涉及何种机制，很明显，包括脂肪组织和肾脏在内的一系列器官内的长期组织特异性适应性变化，会在母体糖皮质激素分泌发生变化后受到极大影响。
