Fig. 6.

The epigenotype model of developmental origins of disease. Environmental factors acting in early life have consequences that become manifest as an altered disease risk in later life. The period of life in which external factors can influence biology extends from conception to the neonatal period and early infancy. It has been suggested that the baby receives from its mother a forecast of the environment it will encounter after birth and modifies its metabolism, whole body physiology, and growth trajectory appropriately to maximize its chances of survival postnatally. However, these adaptations become detrimental if the conditions after birth are not the same as the ones encountered during early life. These adaptations include metabolic and endocrine changes that may lead to lifelong changes in the function and structure of the body—a concept that has been termed programming. The molecular mechanisms by which a phenomenon that occurs in utero has a phenotypic consequence many years later are likely to involve epigenetic mechanisms of gene regulation. Epigenetic marks can be modulated by environmental factors, are heritable, and perpetuate gene-expression changes that underlie programming and may contribute to the onset of disease in later life. Ac, Histone acetylation/active genes; CH3, DNA methylation/silent genes. [Reprinted with permission from I. Sandovici et al.: Epigenetics, Horizon Scientific Press/Caister Academic Press, Norfolk, UK, 2008 (563). © with permission from the publisher]