TY - JOUR T1 - Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.115.068668 SP - dmd.115.068668 AU - Jamie E Moscovitz AU - Muna S Nahar AU - Stuart L Shalat AU - Angela L Slitt AU - Dana C Dolinoy AU - Lauren M Aleksunes Y1 - 2016/01/01 UR - http://dmd.aspetjournals.org/content/early/2016/02/05/dmd.115.068668.abstract N2 - Due to its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples. The mRNA expression of BCRP and MRP4, as well as BCRP and MDR1 exhibited the highest degree of correlation, with r-squared values of 0.941 (p<0.001) and 0.816 (p<0.001), respectively. Increasing concentrations of conjugated BPA significantly correlated with high expression of MRP1 (p<0.001), MRP2 (p<0.05), and MRP3 (p<0.05) transporters, in addition to the transcription factor NRF2 (p<0.001) and its prototypical target gene, NQO1 (p<0.001). These data demonstrate that xenobiotic transporters may be coordinately expressed in the human fetal liver. This is also the first report of a relationship between environmentally-relevant fetal BPA levels and differences in the expression of transporters that can excrete the parent compound and its metabolites. ER -