Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function
Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function
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DOI：
10.1113/jphysiol.2007.147967
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发表时间：
2008-04-15
影响因子：
5.5
通讯作者：
Hanson, Mark A.
中科院分区：
文献类型：
--
作者：
Bertram, Caroline;Khan, Omar;Hanson, Mark A.
围产期环境是晚年患病风险的重要决定因素。在这里，我们已经表明，母亲营养不良会导致两代人的心脏结构和下丘脑-垂体-肾上腺（HPA）功能发生巨大变化。妊娠豚鼠从妊娠第1-35天（早期限制; ER）或36-70天（晚期限制; LR）喂食正常摄入量的70%。雌性后代（F-1）交配并自由采食，以产生第二代（F-2）后代。在雄性F-1和F-2后代中评估心脏形态、血压、压力感受器和HPA功能。ERF 1雄性动物表现出血压升高、左心室（LV）壁厚度和LV质量增加。这些LV效应在ERF 2后代中得以维持。母亲营养不良增加基础皮质醇和改变HPA的反应，在两代的挑战，影响最大的LR组。总之，中度母体营养不良深刻地改变了两代成年男性后代的心脏结构和HPA功能。
The perinatal environment is a powerful determinant of risk for developing disease in later life. Here, we have shown that maternal undernutrition causes dramatic changes in heart structure and hypothalamo-pituitary-adrenal (HPA) function across two generations. Pregnant guinea pigs were fed 70% of normal intake from gestational days 1-35 (early restriction; ER), or 36-70 (late restriction; LR). Female offspring (F-1) were mated and fed ad libitum to create second generation (F-2) offspring. Heart morphology, blood pressure, baroreceptor and HPA function were assessed in male F-1 and F-2 offspring. ERF1 males exhibited elevated blood pressure, increased left ventricular (LV) wall thickness and LV mass. These LV effects were maintained in the ERF2 offspring. Maternal undernutrition increased basal cortisol and altered HPA responsiveness to challenge in both generations; effects were greatest in LR groups. In conclusion, moderate maternal undernutrition profoundly modifies heart structure and HPA function in adult male offspring for two generations.