A conceptual framework for the developmental origins of health and disease
- 9 December 2009
- journal article
- review article
- Published by Cambridge University Press (CUP) in Journal of Developmental Origins of Health and Disease
- Vol. 1 (1), 6-18
- https://doi.org/10.1017/s2040174409990171
Abstract
In the last decades, the developmental origins of health and disease (DOHaD) have emerged as a vigorous field combining experimental, clinical, epidemiological and public health research. Its goal is to understand how events in early life shape later morbidity risk, especially of non-communicable chronic diseases. As these diseases become the major cause of morbidity and mortality worldwide, research arising from DOHaD is likely to gain significance to public health and economic development. But action may be hindered by the lack of a firm mechanistic explanation and of a conceptual basis, especially regarding the evolutionary significance of the DOHaD phenomenon. In this article, we provide a succinct historical review of the research into the relationship between development and later disease, consider the evolutionary and developmental significance and discuss the underlying mechanisms of the DOHaD phenomenon. DOHaD should be viewed as a part of a broader biological mechanism of plasticity by which organisms, in response to cues such as nutrition or hormones, adapt their phenotype to environment. These responses may be divided into those for immediate benefit and those aimed at prediction of a future environment: disease occurs in the mismatch between predicted and realized future. The likely mechanisms that enable plasticity involve epigenetic processes, affecting the expression of genes associated with regulatory pathways. There is now evidence that epigenetic marks may be inherited and so contribute to non-genomic heritable disease risk. We end by discussing the global significance of the DOHaD phenomenon and its potential applications for public health purposes.Keywords
This publication has 105 references indexed in Scilit:
- DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specificHuman Molecular Genetics, 2009
- Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequencesGenome Research, 2009
- Common Genetic Variation and Human TraitsThe New England Journal of Medicine, 2009
- Methyl donor supplementation prevents transgenerational amplification of obesityInternational Journal of Obesity, 2008
- DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine statusProceedings of the National Academy of Sciences of the United States of America, 2007
- Metabolic plasticity during mammalian development is directionally dependent on early nutritional statusProceedings of the National Academy of Sciences of the United States of America, 2007
- Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controlsNature, 2007
- Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modificationsBritish Journal of Nutrition, 2007
- Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life?British Journal of Nutrition, 2007
- Stability and flexibility of epigenetic gene regulation in mammalian developmentNature, 2007