Effect of In Utero and Early-Life Conditions on Adult Health and Disease
A long latency period between an environmental trigger and the onset of subsequent disease is widely recognized in the etiology of certain cancers, yet this phenomenon is not generally considered in the etiology of other conditions such as cardiovascular disease, metabolic disease, or osteoporosis. However, many lines of evidence, including epidemiologic data and data from extensive clinical and experimental studies, indicate that early life events play a powerful role in influencing later susceptibility to certain chronic diseases. An increased understanding of developmental plasticity (defined as the ability of an organism to develop in various ways, depending on the particular environment or setting) provides a conceptual basis for these observations. Developmental plasticity requires stable modulation of gene expression, and this appears to be mediated, at least in part, by epigenetic processes such as DNA methylation and histone modification. Thus, both the genome and the epigenome interactively influence the mature phenotype and determine sensitivity to later environmental factors and the subsequent risk of disease. In this review, we synthesize evidence from several disciplines to support the contention that environmental factors acting during development should be accorded greater weight in models of disease causation.