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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers.

Authors: Moscovitz, Jamie E; Nahar, Muna S; Shalat, Stuart L; Slitt, Angela L; Dolinoy, Dana C; Aleksunes, Lauren M

Published In Drug Metab Dispos, (2016 07)

Abstract: Because of 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 the 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 breast cancer resistance protein (BCRP) and multidrug resistance-associated transporter (MRP)4, as well as BCRP and multidrug resistance transporter 1 exhibited the highest degree of correlation, with r(2) values of 0.941 and 0.816 (P < 0.001 for both), 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 NF-E2-related factor 2 transcription factor (P < 0.001) and its prototypical target gene, NAD(P)H quinone oxidoreductase 1 (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.

PubMed ID: 26851240 Exiting the NIEHS site

MeSH Terms: ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism; Benzhydryl Compounds/metabolism*; Biological Transport; Environmental Pollutants/metabolism*; Female; Gestational Age; Hepatobiliary Elimination*; Humans; Liver/embryology; Liver/metabolism*; Male; Membrane Transport Proteins/genetics; Membrane Transport Proteins/metabolism*; Multidrug Resistance-Associated Proteins/genetics; Multidrug Resistance-Associated Proteins/metabolism; NAD(P)H Dehydrogenase (Quinone)/genetics; NAD(P)H Dehydrogenase (Quinone)/metabolism; NF-E2 Transcription Factor, p45 Subunit/genetics; NF-E2 Transcription Factor, p45 Subunit/metabolism; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Phenols/metabolism*; RNA, Messenger/genetics; RNA, Messenger/metabolism

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