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

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

doi:10.1124/dmd.115.068668

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

Journal article

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

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

Drug metabolism and disposition, Vol.44(7), pp.1061-1065

07/2016

DOI: https://doi.org/10.1124/dmd.115.068668

PMCID: PMC4931889

PMID: 26851240

Abstract

NF-E2 Transcription Factor, p45 Subunit - metabolism

Humans

Male

Environmental Pollutants - metabolism

NAD(P)H Dehydrogenase (Quinone) - genetics

Neoplasm Proteins - metabolism

RNA, Messenger - metabolism

Liver - embryology

ATP Binding Cassette Transporter, Sub-Family G, Member 2 - metabolism

Biological Transport

Membrane Transport Proteins - genetics

Female

Membrane Transport Proteins - metabolism

Multidrug Resistance-Associated Proteins - genetics

Neoplasm Proteins - genetics

NF-E2 Transcription Factor, p45 Subunit - genetics

Hepatobiliary Elimination

Liver - metabolism

RNA, Messenger - genetics

Phenols - metabolism

Gestational Age

ATP Binding Cassette Transporter, Sub-Family G, Member 2 - genetics

NAD(P)H Dehydrogenase (Quinone) - metabolism

Multidrug Resistance-Associated Proteins - metabolism

Benzhydryl Compounds - metabolism

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.

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Title: Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers
Creators: Jamie E Moscovitz - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.)
Muna S Nahar - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.)
Stuart L Shalat - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.)
Angela L Slitt - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.)
Dana C Dolinoy - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.)
Lauren M Aleksunes - Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey (J.E.M., L.M.A.); Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan (M.S.N., D.C.D.); Division of Environmental Health, School of Public Health, Georgia State University, Atlanta, Georgia (S.L.S.); Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey (S.L.S.); Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey (S.L.S., L.M.A.); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island (A.L.S.); and Department of Nutritional Sciences, University of Michigan, Ann Arbor, Michigan (D.C.D.) aleksunes@eohsi.rutgers.edu
Publication Details: Drug metabolism and disposition, Vol.44(7), pp.1061-1065
Date published: 07/2016
Grant note: R01 ES020522 / NIEHS NIH HHS R24 HD000836 / NICHD NIH HHS T32 ES007148 / NIEHS NIH HHS F31 HD082965 / NICHD NIH HHS R01 ES017524 / NIEHS NIH HHS P30 ES017885 / NIEHS NIH HHS T32 ES007062 / NIEHS NIH HHS
Academic Unit: Pharmacology and Toxicology (EMSOP)
Language: English
Resource Type: Journal article
Identifiers: 991031654470904646