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Epigenetic regulation and fetal programming

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Fetal programming encompasses the role of developmental plasticity in response to environmental and nutritional signals during early life and its potential adverse consequences (risk of cardiovascular, metabolic and behavioural diseases) in later life. The first studies in this field highlighted an association between poor fetal growth and chronic adult diseases. However, environmental signals during early life may lead to adverse long-term effects independently of obvious effects on fetal growth. Adverse long-term effects reflect a mismatch between early (fetal and neonatal) environmental conditions and the conditions that the individual will confront later in life. The mechanisms underlying this risk remain unclear. However, experimental data in rodents and recent observations in humans suggest that epigenetic changes in regulatory genes and growth-related genes play a significant role in fetal programming. Improvements in our understanding of the biochemical and molecular mechanisms at play in fetal programming would make it possible to identify biomarkers for detecting infants at high risk of adult-onset diseases. Such improvements should also lead to the development of preventive and therapeutic strategies.

Section snippets

Fetal programming and postnatal diseases: endocrine and metabolic aspects

There are several excellent reviews dealing with the epidemiological evidence for an association between early nutrition and the major risk factors for cardiovascular diseases, insulin resistance, diabetes and metabolic syndrome in adult life, and addressing the critical windows during which perturbations have major effects.*1, *2, 10, 11 In many instances, the disorders associated with suboptimal fetal growth are caused by changes in the development of key endocrine axes, with postnatal

Initiating mechanisms

It is clear that environmental and nutritional factors during early life are determinants for postnatal and adult health, but the mechanisms by which fetal programming by environmental factors is initiated in early life remain unclear.

Conclusion

The human fetus responds to maternal under-nutrition, placental dysfunction, maternal stress, and other environmental influences by changing its physiological development and slowing its growth. These adaptive processes result in a higher risk of chronic adult diseases. At the molecular level, this is reflected in transcriptional changes in metabolic and growth pathways. There is some evidence that some of these changes are achieved by alteration of the epigenetic regulation of genes.

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