Roles of the placenta in fetal brain development.

F ollowing on the seminal observations of Barker and associates (1), maternal hormonal and nutrient environment has been systematically implicated in effects on the developing fetus that ultimately influence susceptibility to a wide range of metabolic, neurodevelopmental, and psychiatric diseases in adulthood (2, 3). There is a growing appreciation that perturbations in the maternal environment are conveyed to the fetus by changes in placental function (4). Two recent studies have identified functions of the murine placenta as the interface between the maternal environment and the developing CNS (5, 6). In response to acute maternal food deprivation, Broad and Keverne (5) find that a program of catabolic gene expression is initiated in the placenta, whereas the hypothalamus is largely spared. These observations raise the possibility that, in circumstances of reduced maternal nutrient availability, the placenta itself may be catabolized to provide critical fuel and structural molecules to the developing hypothalamus. Levitt and collaborators (6) used a novel ex vivo preparation to demonstrate that the placenta can convert maternal tryptophan into the neurotransmitter serotonin (5-hydroxytryptophan; 5-HT), providing the primary source of 5-HT for the developing mouse forebrain at midgestation. Together these studies suggest that the traditional view of the placenta as a passive site of transport of maternal nutrients, growth factors, and hormones needs to be expanded to include a role in supporting CNS development through adaptive responses to the maternal environment.