The Role of the Placenta in Fetal Programming

The placenta occupies a critical place in fetal programming by modulating fetal responses to alterations in the maternal environment, by regulating transfer of nutrients between mother and fetus and by responding to changes in environmental stimuli that affect maternal and/or fetal physiology. Placental size and function are exquisitely sensitive to alterations in maternal nutrition, oxygen tension and exposure to glucocorticoids. These factors affect the activity of proteins such as the System A transporter that shuttles neutral amino acids to the fetus, the activity of cells such as those producing placental lactogen, a key metabolic hormone of pregnancy, and the generation of peptides such as the urocortins, members of the corticotrophin releasing hormone family with pro-and anti-inflammatory activities, and placental 11βhydroxysteroid dehydrogenase-2, which regulates placental metabolism of maternal cortisol. Maternal administration of exogenous synthetic glucocorticoid bypasses this metabolic barrier, programming reductions in fetal body weight and composition, and changing development of the fetal neurologic, pancreatic and hypothalamic-pituitary-adrenal (HPA) axes, leading to altered stress and inflammatory responses, cardiovascular activity and predisposition to insulin resistance in later life. Interestingly, many of these placental functions appear to be regulated in a manner that is dependent upon the sex of the fetus.