RT Journal Article SR Electronic T1 Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP dmd.115.068668 DO 10.1124/dmd.115.068668 A1 Jamie E Moscovitz A1 Muna S Nahar A1 Stuart L Shalat A1 Angela L Slitt A1 Dana C Dolinoy A1 Lauren M Aleksunes YR 2016 UL http://dmd.aspetjournals.org/content/early/2016/02/05/dmd.115.068668.abstract AB 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.