McMullen Sarah, Mostyn Alison
Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough LE12 5RD, UK.
Proc Nutr Soc. 2009 Aug;68(3):306-20. doi: 10.1017/S0029665109001396. Epub 2009 Jun 3.
Human epidemiological studies have indicated that the risk of developing non-communicable diseases in later life may be related to exposures during the developmental period. Developmental life is a vulnerable period of the lifespan during which adverse environmental factors have the potential to disturb the processes of cell proliferation and differentiation or to alter patterns of epigenetic remodelling. Animal models have been instrumental in demonstrating the biological plausibility of the associations observed in human populations, providing proof of principle to the theory of the developmental origins of health and disease (DOHaD). A variety of large- and small-animal models have made important contributions to the field, providing strong evidence of a causal relationship between early-life exposures and metabolic risk factors in later life. Studies of animal models are continuing to contribute to improving the understanding of the mechanisms of the developmental origins of disease. All models have their advantages and disadvantages, and the model that is most appropriate for any particular study is hypotheses dependent. The present review aims to briefly summarise the contributions that animal models have made to the DOHaD field, before reviewing the strengths and weaknesses of these animal models. It is proposed that the integration of evidence from a variety of different models is required for the advancement of understanding within the field.
人类流行病学研究表明,成年后患非传染性疾病的风险可能与发育时期的暴露情况有关。发育阶段是生命历程中的一个脆弱时期,在此期间,不良环境因素有可能干扰细胞增殖和分化过程,或改变表观遗传重塑模式。动物模型有助于证明在人类群体中观察到的关联具有生物学合理性,为健康与疾病的发育起源(DOHaD)理论提供了原理证明。各种大小动物模型都为该领域做出了重要贡献,有力证明了生命早期暴露与成年后代谢风险因素之间的因果关系。动物模型研究继续有助于增进对疾病发育起源机制的理解。所有模型都有其优缺点,最适合任何特定研究的模型取决于假设。本综述旨在简要总结动物模型对DOHaD领域的贡献,然后再探讨这些动物模型的优缺点。有人提出,该领域的进展需要整合来自各种不同模型的证据。