Livestock as models for developmental programming

Infants that are growth-restricted or developmentally compromised (e.g., altered development of specific organs such as the heart or coronary blood vessels) have an increased risk of health complications, not just as infants, but throughout their lives. The health complications include pathological conditions like metabolic disease (cardiovascular disease, diabetes, and obesity) as well as poor immune function, poor reproductive function, poor cognitive function, and pervasive developmental disorders (e.g., autism spectrum). This concept has been named Developmental Origins of Health and Disease, or developmental programming (Armitage et al., 2004; Barker, 2004; Wu et al., 2006; Reynolds et al., 2010b; Reynolds and Caton, 2012; Vonnahme, 2012; Reynolds and Vonnahme, 2016). The basic idea is that a stimulus or insult that occurs in utero or during infancy can have lifelong effects on the health and well-being of an individual. Human epidemiological studies throughout the world have provided convincing support for the concept of developmental programming by showing a strong relationship between low birth weight, or other “developmental insults” such as exposure to stress-related hormones (including corticosteroids, which are widely used clinically to prepare the fetus for birth and to initiate delivery), and the subsequent risk of developing the range of pathologies mentioned in the previous paragraph as adults (Godfrey and Barker, 2000; Armitage et al., 2004; Barker, 2004; Luther et al., 2009; Wallace et al., 2006; Wu et al., 2006; Reynolds et al., 2010b; Reynolds and Caton, 2012; Vonnahme, 2012). As one example, Table 1 shows the strong relationship between birth weight and the odds of developing type 2 (adult onset) diabetes or impaired glucose tolerance (pre-diabetes) in men aged 59 to 70; for example, men who were born in the lowest birth weight category (< 5.5 lb or 2.5 kg) were almost 7 times more likely to develop these pathologies compared with those born in the highest birth weight category (>9.5 lb or 4.3 kg). These and the other pathologies mentioned above have a major impact on the quality of life and lifetime productivity and ultimately will reduce life expectancy. Many epidemiological studies in humans and controlled studies in animal models, including livestock, have identified a host of risk factors that provide the developmental insults that may lead to developmental programming. These risk factors include such things as lifestyle choices, various maternal factors, and environmental exposures (Table 2). Reducing the incidence or impact of such developmental insults has the potential to affect both the immediate survival and the lifelong health of an individual (Reynolds and Caton, 2012; Reynolds and Vonnahme, 2016). Whereas the initial epidemiological studies that led to the concept of developmental programming focused on individuals with low birth weight, we now know that birth weight per se is only a reflection of an Livestock as models for developmental programming