Metabolic programming in pregnancy: studies in animal models

Abstract

Epidemiological studies of many large populations indicate that non-communicable diseases in adulthood are related to factors in fetal life or during infancy [1]. Low birthweight or disproportion at birth are associated with increased risk of cardiovascular disease and type-II diabetes. These associations have been explained in terms of developmental programming, which is the process through which insults or stimuli during early life exert permanent effects upon organ development, physiology and metabolism [18]. Variation in the nutrient supply during fetal has been proposed as the major programming stimulus that determines risk of disease in adulthood. Studies of human cohorts have mainly required the use of retrospective cohorts and this has raised serious issues regarding control for confounding factors, selection bias and measurement bias [11]. Moreover, within relatively well-nourished populations variation in maternal nutrient intakes are noted to have little impact upon patterns of fetal growth or birthweight [17], which has led some observers to question the plausibility of the developmental origins of adult disease hypothesis. Experimental studies employing small animal species (e.g. rat, mouse or guinea pig) or larger species (pig and sheep) have, however, clearly demonstrated the biological plausibility of nutritional programming [25]. A diverse range of nutritional manipulations in pregnancy have been shown to programme profound changes in tissue morphology, physiology and metabolism and often these changes occur independently of fetal growth retardation [25].