The role of the placenta in fetal programming

The rise in rates of non-communicable diseases that emerged over the past 20 years is without precedent. The causes of the epidemic remain enigmatic. The usual explanation, that disease is caused by poor genes or detrimental lifestyle choices are inadequate to explain the rapid time course. However, the work of David Barker and colleagues, published some 25 years ago, showed powerful relationships between low birthweight and risk for adult onset type 2 diabetes and offered new ways of thinking regarding the origins of chronic disease. It is now evident that (i) programming later life health or disease begins at conception or earlier, at different windows of developmental plasticity through altered structural or epigenetic responses; (ii) prenatal changes predispose to altered post natal environmental responses (epigenome x environment, E2, interaction) and (iii) the placenta has a central role in mediating these effects. While the placenta is known to be the conduit through which maternal nutrients reach the embryo and fetus, the mechanisms that underlie the transport of the vast number of nutrients is complex and includes, diffusion, active transport and vesicular transport. These transport systems are influenced by maternal body composition and physiological state. The predilection for various chronic diseases among adults is associated with placental size and shape. The physiological features of the maternal, fetal and placental units are important in regulating transport function of the placenta. Levels of 11β hydroxysteroid dehydrogenase influence the degree to which maternal cortisol reaches the fetal circulation. Maternal under and over-nutritional states affect the fetal HPA axis beyond birth. Five year old offspring of periconceptional undernourished ewes have reduced hypothalamic GR promoter methylation, increased levels of glucocorticoid receptor mRNA and protein and increased adiposity. Thus, the research task of the next generation will be to determine 1) the appropriate use of glucocorticoids in clinical practice balancing potential detrimental effects on offspring, 2) the roles of maternal nutritional state before and during pregnancy and their short term effects on placental function and long term effects on offspring and 3) the degree to which biomarkers associated with maternal conditions can predict disease in offspring.