Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows

The maternal nutritional and metabolic environment is critical in determining not only reproduction, but also long-term health and viability. In the present review, the effects of maternal nutritional manipulation at defined stages of gestation coinciding with embryogenesis, maximal placental or fetal growth will be discussed. Long-term outcomes from these three developmental windows appear to be very different, with brain and cardiovascular function being most sensitive to influences in the embryonic period, the kidney during placental development and adipose tissue in the fetal phase. In view of the similarities in fetal development, number and maturity at birth, there are close similarities in these outcomes between findings from epidemiological studies in historical human cohorts and nutritional manipulation of large animals, such as sheep. One key nutrient that may modulate the long-term metabolic effects is the supply of glucose from the mother to the fetus, because this is sensitive to both global changes in food intake, maternal glucocorticoid status and an increase in the carbohydrate content of the diet. The extent to which these dietary-induced changes may reflect epigenetic changes remains to be established, especially when considering the very artificial diets used to induce these types of effects. In summary, the maintenance of a balanced and appropriate supply of glucose from the mother to the fetus may be pivotal in ensuring optimal embryonic, placental and fetal growth. Increased or decreased maternal plasma glucose alone, or in conjunction with other macro- or micronutrients, may result in offspring at increased risk of adult diseases.