Our proposal tests the hypotheses that polybrominated diphenyl ethers (PBDEs) and their metabolites (OH- PBDEs) accumulate differently in the human fetal liver and placenta than in maternal serum, and that fetal exposure to PBDEs affects fetal metabolic capacity. Virtually all pregnant women in the United States are exposed to at least one and often multiple PBDEs, a class of persistent organic chemicals widely used as flame retardants in consumer products since the 1970s. PBDEs are an important public health concern, as in vitro and in vivo studies show that in utero exposure can adversely impact fetal development. Human exposure and epidemiologic studies have largely characterized in utero exposure by measuring chemicals in proxy biological specimens, such as maternal blood and umbilical cord blood collected at delivery. These samples are not necessarily representative of fetal exposures earlier in pregnancy, particularly to target organs of concern such as the liver and placenta. We propose to measure levels of PBDEs and OH-PBDEs in human maternal and fetal biological specimens from women undergoing voluntary, second trimester pregnancy terminations. Because data on chemical-induced changes in human fetal metabolic capacity are critical to understanding mechanisms of in utero toxicity but are currently lacking, we will also generate original human data on whether fetal exposures to PBDEs alter gene expression of cytochrome P450 (CYP) enzymes in the second-trimester human fetal liver and placenta. At the end of this study, we will produce unique information about human fetal exposure to PBDEs and OH-PBDEs during the second trimester, including empirical relationships between maternal and fetal exposures which can be used to estimate fetal exposures when only maternal levels are available. Further, this will be the first ever in vio data on the relationship between PBDE exposure and human fetal CYP activity. Collectively, this information will help bridge the gap between experimental toxicology and human observation studies and will improve our understanding of population risks to PBDEs as well as other structurally similar environmental chemicals that interact with xenobiotic-sensing nuclear receptors. Pregnant women in the United States are widely exposed to a group of flame retardant chemicals called polybrominated diphenyl ethers (PBDEs), which interfere with the development of a fetus during pregnancy, resulting in endocrine, liver, reproductive, and neurodevelopmental harm. Although many forms of these flame retardants have been phased out, these chemicals persist in the environment and pregnant women will continue to be exposed to them. Our research will produce novel data on human maternal and fetal exposure to PBDEs during the 2nd trimester of pregnancy, and their influence on metabolic pathways in the fetus, critical to understanding developmental risks from PBDEs and other structurally related chemicals.