Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives
Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives
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DOI：
10.1210/en.2015-1350
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发表时间：
2015-10-01
期刊：
影响因子：
4.8
通讯作者：
Heindel, Jerrold J.
中科院分区：
文献类型：
--
作者：
Grandjean, Philippe;Barouki, Robert;Heindel, Jerrold J.
健康与疾病的发展起源（DOHaD）范式是生物医学研究中发展最快的领域之一。可能影响DOHaD的环境压力因素包括各种环境和职业危害以及营养和能量的缺乏和过度供应。它们可能会扰乱早期发育过程，并导致晚年对疾病/功能障碍的易感性增加。2014年10月在波士顿举行的第四次产前规划和毒性会议上的发言提供了重要的见解，并为研究和公共卫生行动提出了新的建议。会议强调了早在孕前时期就可能出现的脆弱暴露窗口，以及表观遗传学作为一种主要机制，可能导致基因组的不利“重新编程”，从而可能导致跨代影响。干细胞也可能是环境压力的目标，从而为可能持续一生的影响铺平了另一条道路。目前的测试模式不允许正确的风险因素及其相互作用的特点。因此，必须从人体接触情况和结果评估中确定用于测试的相关接触水平和组合。测试潜在的基础机制和生物标志物的开发需要实验室动物模型和体外方法。只有少数几个大规模的出生群组，应促进全球范围内出生群组之间的合作。多哈的研究在确定导致有害结果的因素和制定早期预防/补救战略以应对这些风险方面发挥着至关重要的作用。
The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous "reprogramming" of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks.