Department of Health and Human Services, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Am J Clin Nutr. 2011 Dec;94(6 Suppl):1939S-1942S. doi: 10.3945/ajcn.110.001057. Epub 2011 Nov 16.
Many chemicals in the environment, especially those with estrogenic activity, are able to disrupt the programming of endocrine signaling pathways established during development; these chemicals are referred to as endocrine-disrupting chemicals. Altered programming can result in numerous adverse consequences in estrogen-target tissues, some of which may not be apparent until later in life. For example, a wide variety of structural, functional, and cellular effects have been identified in reproductive tract tissues. In addition to well-documented reproductive changes, obesity and diabetes have joined the list of adverse effects that have been associated with developmental exposure to environmental estrogens and other endocrine-disrupting chemicals. Obesity is a significant public health problem reaching epidemic proportions worldwide. Experimental animal studies document an association of developmental exposure to environmental estrogens and obesity. For example, a murine model of perinatal exposure to diethylstilbestrol has proven useful in studying mechanisms involved in abnormal programming of differentiating estrogen-target tissues, including reproductive tract tissues and adipocytes. Other environmental estrogens, including the environmental contaminant bisphenol A, have also been linked to reproductive problems and obesity later in life. Epidemiology studies support similar findings in humans, as do studies of cells in culture. Together, these findings suggest new targets for abnormal programming by estrogenic chemicals and provide evidence supporting the scientific concept termed the developmental origins of adult disease. Furthermore, the association of environmental estrogens with obesity and diabetes expands the focus on these diseases from intervention or treatment to include prevention or avoidance of chemical modifiers, especially during critical windows of development.
环境中的许多化学物质，特别是那些具有雌激素活性的化学物质，能够破坏在发育过程中建立的内分泌信号通路的编程；这些化学物质被称为内分泌干扰物。编程的改变会导致雌激素靶组织中出现许多不良后果，其中一些后果可能要到以后的生活中才会显现出来。例如，在生殖道组织中已经确定了各种各样的结构、功能和细胞效应。除了有充分记录的生殖变化外，肥胖和糖尿病也加入了与环境雌激素和其他内分泌干扰物的发育接触相关的不良影响的清单。肥胖是一个严重的公共卫生问题，在全球范围内达到了流行的程度。实验动物研究记录了环境雌激素和肥胖之间的发育接触的关联。例如，围产期暴露于己烯雌酚的小鼠模型已被证明可用于研究异常分化的雌激素靶组织编程（包括生殖道组织和脂肪细胞）所涉及的机制。其他环境雌激素，包括环境污染物双酚 A，也与以后生活中的生殖问题和肥胖有关。流行病学研究在人类中支持类似的发现，培养细胞的研究也是如此。这些发现共同表明，雌激素类化学物质的异常编程有了新的目标，并为支持发育起源于成年疾病的科学概念提供了证据。此外，环境雌激素与肥胖和糖尿病的关联将这些疾病的关注点从干预或治疗扩展到包括预防或避免化学修饰剂，特别是在发育的关键窗口期。
