Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Placenta. 2012 Nov;33 Suppl 2:e40-4. doi: 10.1016/j.placenta.2012.07.018. Epub 2012 Aug 14.
Suboptimal intrauterine conditions, including poor nutrition, during critical periods of growth may lead to lifelong changes in the body's organs and tissues, thus providing a physiological basis for adult-onset disease. Remarkably, recent evidence suggests that the long-term consequences of adverse conditions during early development may not be limited to one generation, but may lead to poor health in the generations to follow, even if these individuals develop in normal conditions themselves. For example, the diet of a pregnant mother may affect the development and disease risk of her children and even her grandchildren. There is limited evidence for this in humans since studies of multiple generations are difficult to maintain. However, recent animal models have been generated to investigate this phenomenon and will be instrumental in the future for assessing the underlying mechanisms of intergenerational and transgenerational transmission of disease. These mechanisms remain unclear, though environmental, metabolic and epigenetic factors are likely involved. Researchers have begun to address how changes in metabolism and epigenetic regulation of gene expression caused by poor nutrition can be passed from one generation to the next. Ultimately, these findings will shed light on the transmission of diabetes, obesity and cardiovascular disease that are rapidly expanding in Western countries. Public health strategies that focus on improved maternal nutrition may provide a means of promoting cardiovascular and metabolic health. However, the full impact of these strategies may not be apparent for decades.
宫内环境不良，包括生长关键期的营养缺乏，可能导致机体器官和组织发生终生变化，从而为成年期疾病提供生理基础。值得注意的是，最近的证据表明，早期发育过程中不良条件的长期后果可能不仅局限于一代，还可能导致后续几代人健康状况不佳，即使这些个体本身在正常条件下发育。例如，孕妇的饮食可能会影响其子女甚至孙辈的发育和疾病风险。由于很难维持几代人的研究，人类对此类证据的了解有限。但是，最近已经产生了用于研究这种现象的动物模型，这对于评估疾病在代际和跨代传递的潜在机制将具有重要意义。尽管环境、代谢和表观遗传因素可能涉及其中，但这些机制仍不清楚。研究人员已经开始研究由营养不良引起的代谢和基因表达的表观遗传调控变化如何从一代传递到下一代。最终，这些发现将揭示在西方国家迅速蔓延的糖尿病、肥胖和心血管疾病的传播机制。关注改善孕产妇营养的公共卫生策略可能为促进心血管和代谢健康提供一种手段。但是，这些策略的全部影响可能在几十年后才会显现。
