School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK.
Proc Nutr Soc. 2013 Aug;72(3):317-25. doi: 10.1017/S0029665112003035. Epub 2013 Jan 14.
The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under- or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena.
健康与疾病起源假说认为，胎儿在发育过程中暴露于不理想的母体环境会影响生理功能，并决定成年后患疾病的风险。大量证据表明这种编程来自回顾性的流行病学队列研究，这些研究表明出生时的人体测量学与成年期的非传染性疾病之间存在关联。断言母体营养的变化驱动这些关联得到了使用动物模型的研究的支持，这些研究表明，怀孕期间母体营养不足或过剩会影响后代的发育。通常，在怀孕期间营养不良的动物的后代表现出相对狭窄的生理表型范围，包括更高的血压、葡萄糖不耐受、肾功能不全和肥胖增加。从非常不同的母体营养损伤中出现常见表型的观察结果导致了编程是由少数机制过程驱动的假设。由于内分泌失衡或限制胎儿中关键营养物质的过程，母体营养状态对组织的重塑可能导致器官结构不可逆转地改变，从而限制其随着年龄增长的功能。有人提出，母体饮食可能会影响决定胎儿组织中基因表达的表观遗传标记，这可能是连接母体营养摄入与后代表型长期编程的重要机制。本次综述的目的是提供胎儿编程的机制基础概述，展示动物模型作为研究编程现象的工具的关键作用。
