Developmental origins of health and disease: New insights
Developmental origins of health and disease: New insights
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DOI：
10.1111/j.1742-7843.2007.00186.x
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Gluckman, Peter D.
中科院分区：
文献类型：
--
作者：
Hanson, Mark A.;Gluckman, Peter D.
流行病学和动物研究表明，发育环境的微小变化可以引起表型变化，影响个体对后来环境的反应。这些可能会改变患慢性疾病的风险，如代谢综合征或心血管疾病。最近的研究表明，暴露在出生前和出生后环境不匹配的动物会出现肥胖、活动减少、瘦素和胰岛素抵抗、血压升高和血管内皮功能障碍。表观遗传过程参与了这种效应，目标是特定组织中特定基因的启动子区域。这种对基因表达的精细控制表明，这些机制通过它们的适应优势在进化中得以保留，而不是代表类似于畸形发生的发育中断的极端影响。在一条发育线索中可能存在适应性优势，该线索可以在直接怀孕之后的世代中诱导表型变化，并且有一系列数据支持这一概念。在动物身上，DNA甲基化等表观遗传效应可以遗传给后代。环境毒素，包括内分泌干扰物，如果影响正常的发育表观遗传过程，即使在低水平暴露，也可能导致更大的慢性病风险。适当的干预措施可能会产生长期的多代影响，以降低慢性病的风险。
Epidemiological and animal studies show that small changes in the developmental environment can induce phenotypic changes affecting an individual's responses to their later environment. These may alter the risk of chronic disease such as metabolic syndrome or cardiovascular disease. Recent research shows that animals exposed to such a mismatch between prenatal and postnatal environment develop obesity, reduced activity, leptin and insulin resistance, elevated blood pressure and vascular endothelial dysfunction. Epigenetic processes are involved in such effects, targeted to promoter regions of specific genes in specific tissues. Such fine control of gene expression suggests that the mechanisms have been retained through evolution through their adaptive advantage, rather than representing extreme effects of developmental disruption akin to teratogenesis. There may be adaptive advantage in a developmental cue inducing a phenotypic change in generations beyond the immediate pregnancy, and a range of data that support this concept. In animals, epigenetic effects such as DNA methylation can be passed to successive generations. Environmental toxins, including endocrine disruptors, may induce greater risk of chronic disease, even at low exposure levels, if they affect such normal developmental epigenetic processes. Appropriate interventions may have long-term multigenerational effects to reduce the risk of chronic disease.