ESPE Abstracts (2015) 84 S5.2

Transgenerational Developmental Programming of Endocrine Disease

Susan Ozanne

University of Cambridge, Cambridge, UK

It has been recognized for over 20 years that there is an association between patterns of early growth and long-term risk of traditionally adult onset diseases such as type 2 diabetes. This has been observed both in human epidemiological studies and in animal models. This led to the concept of the developmental origins of health and disease that suggests that the environment to which an individual is exposed during critical periods of development, such as the in utero period, has a permanent impact on our long-term health.

One important early environmental factor known to have such programming effects is nutrition. Initial studies focussed on the detrimental effects of low birth weight and early under-nutrition. However in light of the growing epidemic of obesity, more and more focus is now being directed towards the detrimental effects of early over-nutrition. Fetal under-nutrition and fetal over-nutrition appear to have a very similar phenotypic consequence in terms of metabolic disease risk. However it is yet to be established if they mediate their effects through the same mechanistic pathways. In recent years considerable progress has been made in defining these mechanisms by which an event in early life can have a long-term phenotypic consequence. Three key programming mechanisms have emerged: i) permanent structural changes – the idea that if during a critical period of development an organ is exposed to a suboptimal level of a key hormone or nutrient required for its development this will permanent impact on organ structure and consequently function, ii) accelerated cellular ageing as a consequence of increased oxidative stress and iii) epigenetic programming of gene expression through changes in DNA methylation, histone modifications and/or miRNAs. Further understanding of these mechanisms may give us the potential to develop markers of disease risk and aid the design of rational intervention strategies.

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