2002 International International Biennial Scientific Meeting

THE EARLY ORIGINS OF ADULT DISEASE: PARENTING BEFORE AND AFTER BIRTH

Caroline McMillen

Research Centre for the Physiology of Early Development, Department of Physiology, The University of Adelaide

caroline.mcmillen@adelaide.edu.au

A world wide series of epidemiological studies has shown that poor intrauterine growth is associated with an increased prevalence of cardiovascular disease, non insulin dependent diabetes mellitus and the Metabolic Syndrome in adult life. It has been postulated that a reduced intrauterine nutrient supply perturbs fetal growth and concomitantly alters or programs the structure and function of developing systems. There are a range of pathophysiological factors which may result in a perturbation or restriction of fetal growth which include gene defects, chromosomal abnormalities, poor placental function, maternal smoking, maternal alcohol or drug abuse and poor maternal nutrition. The mechanisms by which these factors alter the pattern of fetal growth vary and the physiological adaptations of the fetus to these stimuli will depend on their nature, timing and intensity. The physiological adaptations of the fetus to an adverse intrauterine environment are in turn clearly important in determining the immediate and longer term consequences for the health and well being of the fetus, newborn and adult. Whilst restriction of placental function and maternal undernutrition may each impact on fetal growth, there may be important differences in the fetal neuroendocrine and physiological adaptations to these stimuli which result in different outcomes for the fetus and adult. Recent work has shown that poor placental function or inadequate maternal nutrition each result in an altered fetal substrate supply, an increased exposure of fetal tissues to glucocorticoids and specific changes in the regulation of arterial blood pressure through different mechanistic pathways. Furthermore it has been demonstrated that the timing, type and duration of maternal nutrient restriction are each important in determining the fetal adaptive responses and their pathophysiological sequelae in later life. These experimental studies provide a mechanistic basis upon which to identify the key elements of the causal pathways which underpin the early origins of adult disease and the associated opportunities for therapeutic intervention. One intriguing possibility that will be highlighted in this presentation is that patterns of parenting after birth may ameliorate some of the impact of a poor intrauterine environment to limit the consequences of the early programming of adult disease.