Animal models that elucidate basic principles of the developmental origins of adult diseases
Animal models that elucidate basic principles of the developmental origins of adult diseases
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DOI：
10.1093/ilar.47.1.73
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发表时间：
2006-01-01
期刊：
影响因子：
2.5
通讯作者：
Nathanielsz, PW
中科院分区：
文献类型：
--
作者：
Nathanielsz, PW
人类流行病学和动物实验室研究表明，子宫内和新生儿早期的次优环境会改变发育，并使个体容易出现终身健康问题。成人疾病的发育起源的概念已经被广泛接受，因为令人信服的动物研究已经精确地定义了特定暴露的结果，如营养限制，怀孕期间过度喂养，母亲压力和外源性给药糖皮质激素。这篇综述的重点是使用动物模型来评估高血压、糖尿病、肥胖和后代日后垂体肾上腺功能改变的发育过程中涉及的暴露、机制和结果。发展规划的十个原则被描述为基本的，不管在发展过程中暴露和生理系统参与改变的结果。这10条原则在所涉及的生理系统和动物模型研究的背景下进行了讨论，以评估暴露、机制和结果。例如，胎儿对缺氧和营养限制等挑战的反应有助于确保其生存，但这种“发育可塑性”可能会产生长期后果，可能对成年生活不利。为了理解发育规划，它代表了自然和后天的相互作用，有必要整合整个动物系统生理学，体外细胞生物学，基因组和蛋白质组学方法，并使用仔细表征并适合研究问题的动物模型。动物模型在这一评估中发挥着重要作用，因为它们允许在暴露和随后的发育反应期间的不同关键时间窗进行体内和体外联合研究。
Human epidemiological and animal laboratory Studies show that suboptimal environments in the womb and during early neonatal life alter development and predispose the individual to lifelong health problems. The concept of the developmental origins of adult diseases has become well accepted because of the compelling animal studies that have precisely defined the outcomes of specific exposures Such as nutrient restriction, overfeeding during pregnancy, maternal stress, and exogenously administered glucocorticoids. This review focuses on the use of animal models to evaluate exposures, mechanisms, and Outcomes involved in developmental programming of hypertension, diabetes, obesity, and altered pituitary-adrenal function in offspring in later life. Ten principles of developmental programming are described as fundamental, regardless of the exposure during development and the physiological system involved in the altered outcome. The 10 principles are discussed in the context of the physiological systems involved and the animal model studies that have been conducted to evaluate exposures, mechanisms, and outcomes. For example, the fetus responds to challenges such as hypoxia and nutrient restriction in ways that help to ensure its Survival, but this "developmental plasticity" may have long-term consequences that may not be beneficial in adult life. TO understand developmental programming, which represents the interaction of nature and nurture, it is necessary to integrate whole animal systems physiology, in vitro cellular biology, and genomic and proteomic approaches, and to use animal models that are carefully characterized and appropriate for the questions under study. Animal models play an important role in this evaluation because they permit combined in vivo and in vitro study at different critical time windows during the exposure and the ensuing developmental responses.