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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication

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 July 2016, 44 (7) 1061-1065; DOI: https://doi.org/10.1124/dmd.115.068668
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.)
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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.)
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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.)
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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.)
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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.)
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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.)
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    Fig. 1.

    Univariate modeling of gene expression and conjugated BPA levels in fetal livers. Linear regressions for NRF2 mRNA, NQO1 mRNA, MRP1 mRNA, and conjugated BPA levels are shown. Data are presented as mean relative expression (n = 49, normalized to β-2-microglobulin). Dashed lines represent 95% confidence limits. B2M, β-2-microglobulin.

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    TABLE 1

    Correlation matrix for sample characteristics

    Summary of the correlations between different BPA species concentrations and gestational age. A value of 1.0 represents a perfect correlation.

    CharacteristicTotal BPAConjugated BPAFree BPAGestational Age
    Total BPA1.00
    Conjugated BPA0.748*1.00
    Free BPA0.963*0.539*1.00
    Gestational age0.1990.0670.2241.00
    • * P < 0.001.

    • View popup
    TABLE 2

    Normalized gene expression correlation matrix

    Summary of the correlations between gene expression of different transcription factors and transporters in human fetal liver. A value of 1.0 represents a perfect correlation.

    GeneMRP1MRP2MRP3MRP4MDR1BCRPNRF2NQO1
    MRP11.00
    MRP20.739*1.00
    MRP30.462*0.301***1.00
    MRP40.380**0.1690.741*1.00
    MDR10.320***0.1470.689*0.734*1.00
    BCRP0.370**0.2120.796*0.941*0.816*1.00
    NRF20.418**0.2350.315***0.2660.2660.2641.00
    NQO10.859*0.597*0.300***0.302***0.1670.2330.475*1.00
    • * P < 0.001; **P < 0.01; ***P < 0.05.

    • View popup
    TABLE 3

    Regression coefficients for gene expression and BPA levels in human fetal livers

    Regression coefficients (β) were calculated from simple linear regression analysis for each gene and BPA species (n = 49).

    GeneBPA Species
    TotalConjugatedFree
    βP ValueβP ValueβP Value
    MRP11.45 × 10−30.6661.13 × 10−2<0.001*4.36 × 10−40.728
    MRP23.79 × 10−40.8155.54 × 10−30.038**−3.14 × 10−40.779
    MRP38.82 × 10−40.3507.12 × 10−30.013**2.26 × 10−40.851
    MRP41.19 × 10−30.1854.79 × 10−30.0851.11 × 10−30.332
    MDR15.16 × 10−40.6773.37 × 10−30.3802.62 × 10−40.868
    BCRP1.03 × 10−30.2884.45 × 10−30.1389.08 × 10−40.462
    NRF21.82 × 10−30.0571.04 × 10−2<0.001*1.19 × 10−30.334
    NQO11.66 × 10−30.1241.27 × 10−2<0.001*1.19 × 10−30.334
    • * P < 0.001; **P < 0.05.

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    • Supplemental Table -

      qPCR primer sequences

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Drug Metabolism and Disposition: 44 (7)
Drug Metabolism and Disposition
Vol. 44, Issue 7
1 Jul 2016
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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication

BPA and Efflux Transporters in 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 July 1, 2016, 44 (7) 1061-1065; DOI: https://doi.org/10.1124/dmd.115.068668

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Rapid CommunicationSpecial Section on Pediatric Drug Disposition and Pharmacokinetics—Short Communication

BPA and Efflux Transporters in 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 July 1, 2016, 44 (7) 1061-1065; DOI: https://doi.org/10.1124/dmd.115.068668
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