Mark Hanson

Developmental origins of non-communicable disease: Implications for research and public health.

This White Paper highlights the developmental period as a plastic phase, which allows the organism to adapt to changes in the environment to maintain or improve reproductive capability in part through sustained health. Plasticity is more prominent prenatally and during early postnatal life, i.e., during the time of cell differentiation and specific tissue formation. These developmental periods are highly sensitive to environmental factors, such as nutrients, environmental chemicals, drugs, infections and other stressors. Nutrient and toxicant effects share many of the same characteristics and reflect two sides of the same coin. In both cases, alterations in physiological functions can be induced and may lead to the development of non-communicable conditions. Many of the major diseases – and dysfunctions – that have increased substantially in prevalence over the last 40 years seem to be related in part to developmental factors associated with either nutritional imbalance or exposures to environmental chemicals. The Developmental Origins of Health and Disease (DOHaD) concept provides significant insight into new strategies for research and disease prevention and is sufficiently robust and repeatable across species, including humans, to require a policy and public health response. This White Paper therefore concludes that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages.

The Fetal Matrix: Evolution, Development and Disease: The biology of predictive adaptive responses

The combination of experimental, clinical and epidemiological data relating an adverse perinatal environment to long-term outcome has one particularly striking feature. That is, despite the variety of models examined, there is a remarkable consistency in the phenotype that emerges in adulthood. The common features include a tendency to insulin resistance, increased blood pressure, vascular endothelial dysfunction, altered lipid and carbohydrate metabolism, a tendency to obesity and small muscle mass. We have termed this the survival phenotype for reasons that are discussed below. This raises two important questions. First, why is it so easy to produce a consistent phenotype from such a variety of prenatal environments? Second, what is the biological basis for the development of this phenotype? The answers to these questions need to apply to both humans and animals because the PARs theory applies across species. In turn this leads to the more general question of the fundamental biological mechanisms underpinning PARs. These fundamental mechanisms must be independent of whether the PARs that are induced in utero are subsequently appropriate or inappropriate. They are also likely to be independent of the specific intrauterine situation in which they arose. These questions are the focus of this chapter. Such questions can be asked at several levels. At one level there are a set of issues about the nature of the environmental cues that the embryo and fetus respond to, and secondly about when in development these cues act.