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Review ArticleMINIREVIEW

The Role of the Placenta in Fetal Exposure to Xenobiotics: Importance of Membrane Transporters and Human Models for Transfer Studies

Caroline Prouillac and Sylvaine Lecoeur
Drug Metabolism and Disposition October 2010, 38 (10) 1623-1635; DOI: https://doi.org/10.1124/dmd.110.033571
Caroline Prouillac
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Sylvaine Lecoeur
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Abstract

The placenta is a key organ in fetal growth and development because it controls maternal-to-fetal exchanges of nutrients and hormones. It also interferes with drug delivery to the fetus by expressing active membrane transporters and xenobiotic metabolism enzymes. Developing strategies to understand the role of the placenta in drug delivery is a challenge in toxicology. Despite common physiological functions, the placentas of different species are heterogeneous in their morphology and in their expression of membrane transporters and metabolizing proteins. These characteristics raise the difficulty of obtaining a good representative model of human placental transfer. To date, different in vitro, in vivo, and ex vivo tools have been used to elucidate transport and metabolism processes in the human placenta. This study recapitulates the typical features of human placenta and then presents the placental enzymes of xenobiotic metabolism, ATP-binding cassette transporters, solute carrier transporters, and their role in fetal exposure to xenobiotics. The study also compares the characteristics of different models of human placenta, in terms of membrane localization of transporters, and the expression of xenobiotic metabolism enzymes. The use of these models for toxicological studies, in particular xenobiotic transfer, is described, and the advantages and limits of each model are summarized.

Footnotes

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

    doi:10.1124/dmd.110.033571.

  • ABBREVIATIONS:

    P450
    cytochrome P450
    ABC
    ATP-binding cassette
    MDR1, ABCB1
    multidrug resistance-associated proteins
    P-gp
    P-glycoprotein
    PSC833
    6-{(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic} cyclosporine D. GG918, N-{4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl}-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine
    MRPs, ABCCs
    multidrug resistance proteins
    BCRP
    ABCG2, breast cancer resistance proteins
    PhIP
    2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
    SLC
    solute carrier
    OATP
    organic anion-transporting polypeptide
    OAT
    organic anion transporter
    OCT
    organic cation transporter
    OCTN
    organic cation/carnitine transporter
    SERT
    serotonin transporter
    NET
    norepinephrin transporter
    MCT
    monocarboxylate transporter
    ENT
    equilibrative nucleoside transporter
    FRα
    folate receptor alpha
    RFC-1
    reduced folate carrier 1
    PCFT/HCP1
    proton-coupled folate transporter/heme carrier protein 1
    hCG
    human chorionic gonadotropin
    IFN
    interferon
    IL
    interleukin
    ASCT
    amino acid transporter
    SNP
    single nucleotide polymorphism.

  • Received March 26, 2010.
  • Accepted July 6, 2010.
  • Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 38 (10)
Drug Metabolism and Disposition
Vol. 38, Issue 10
1 Oct 2010
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Review ArticleMINIREVIEW

The Role of the Placenta in Fetal Exposure to Xenobiotics: Importance of Membrane Transporters and Human Models for Transfer Studies

Caroline Prouillac and Sylvaine Lecoeur
Drug Metabolism and Disposition October 1, 2010, 38 (10) 1623-1635; DOI: https://doi.org/10.1124/dmd.110.033571

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Review ArticleMINIREVIEW

The Role of the Placenta in Fetal Exposure to Xenobiotics: Importance of Membrane Transporters and Human Models for Transfer Studies

Caroline Prouillac and Sylvaine Lecoeur
Drug Metabolism and Disposition October 1, 2010, 38 (10) 1623-1635; DOI: https://doi.org/10.1124/dmd.110.033571
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  • Article
    • Abstract
    • Introduction
    • Physiological Function of the Human Placental Barrier
    • Enzymes of Xenobiotic Metabolism Content
    • Membrane Transport in Placenta
    • ABC Transporters
    • Solute Carrier Transporters
    • Variation of Transporter Expression during Pregnancy
    • The Use of Cell Lines as Placental Barrier Models
    • Human Choriocarcinoma Cell Lines
    • Human Primary Cells
    • Other Models for Placental Transfer Studies
    • Conclusions and Perspectives
    • Footnotes
    • References
  • Figures & Data
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  • eLetters
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  • Blood-Testis Barrier Drug Transport Models
  • Application of endogenous biomarkers for drug transporters
  • Use of crypt-derived enterocytes to predict drug absorption
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