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Research ArticleArticle

Conjugation and Deconjugation Reactions within the Fetoplacental Compartment in a Sheep Model: A Key Factor Determining Bisphenol A Fetal Exposure

Tanguy Corbel, Elisabeth Perdu, Véronique Gayrard, Sylvie Puel, Marlène Z. Lacroix, Catherine Viguié, Pierre-Louis Toutain, Daniel Zalko and Nicole Picard-Hagen
Drug Metabolism and Disposition April 2015, 43 (4) 467-476; DOI: https://doi.org/10.1124/dmd.114.061291
Tanguy Corbel
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Elisabeth Perdu
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Véronique Gayrard
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Sylvie Puel
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Marlène Z. Lacroix
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Catherine Viguié
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Pierre-Louis Toutain
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Daniel Zalko
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Nicole Picard-Hagen
Institut National de Recherche Agronomique, Unité Mixte de Recherche 1331, Toxalim, Research Centre in Food Toxicology, F-31027; and Université de Toulouse, Institut National Polytechnique de Toulouse, Ecole Nationale Vétérinaire de Toulouse, Ecole d’Ingénieur de Purpan, Université Paul Sabatier, F-31076, Toulouse, France
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Abstract

The widespread human exposure to bisphenol A (BPA), an endocrine disruptor targeting developmental processes, underlines the need to better understand the mechanisms of fetal exposure. Animal studies have shown that at a late stage of pregnancy BPA is efficiently conjugated by the fetoplacental unit, mainly into BPA-glucuronide (BPA-G), which remains trapped within the fetoplacental unit. Fetal exposure to BPA-G might in turn contribute to in situ exposure to bioactive BPA, following its deconjugation into parent BPA at the level of fetal sensitive tissues. The objectives of our study were 1) to characterize the BPA glucurono- and sulfoconjugation capabilities of the ovine fetal liver at different developmental stages, 2) to compare hepatic conjugation activities in human and sheep, and 3) to evaluate the extent of BPA conjugation and deconjugation processes in placenta and fetal gonads. At an early stage of pregnancy, and despite functional sulfoconjugation activity, ovine fetuses expressed low hepatic BPA conjugation capabilities, suggesting that this stage of development represents a critical window in terms of BPA exposure. Conversely, the late ovine fetus expressed an efficient detoxification system that metabolized BPA into BPA-G. Hepatic glucuronidation activities were quantitatively similar in adult sheep and humans. In placenta, BPA conjugation and BPA-G deconjugation activities were relatively balanced, whereas BPA-G hydrolysis was systematically higher than BPA conjugation in gonads. The possible reactivation of BPA-G into BPA could contribute to an increased exposure of fetal sensitive tissues to bioactive BPA in situ.

Footnotes

    • Received September 21, 2014.
    • Accepted January 6, 2015.
  • This work was supported by the French Région Midi-Pyrénées [APRTCN 100551322] and by the French National Research Agency [ANR-13-CESA0007-1].

  • Part of this work was presented as follows: Corbel T, Perdu E, Lacroix MZ, Puel S, Gayrard V, Viguié C, Toutain PL, Zalko D, and Picard-Hagen N (2012) The free/conjugated bisphenol A ratio in fetoplacental compartment: a key parameter determining bisphenol A prenatal exposure. Connaissances récentes sur les effets des perturbateurs endocriniens sur l’environnement et la santé; 2012 Dec 10–11; Paris, France. Ministère de l’Écologie et du Développement Durable et de l’Énergie/National Endocrine Disrupter Research Programme (PNRPE), Paris, France.

  • dx.doi.org/10.1124/dmd.114.061291.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 43 (4)
Drug Metabolism and Disposition
Vol. 43, Issue 4
1 Apr 2015
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Research ArticleArticle

Fetoplacental BPA Conjugation/Deconjugation Reactions

Tanguy Corbel, Elisabeth Perdu, Véronique Gayrard, Sylvie Puel, Marlène Z. Lacroix, Catherine Viguié, Pierre-Louis Toutain, Daniel Zalko and Nicole Picard-Hagen
Drug Metabolism and Disposition April 1, 2015, 43 (4) 467-476; DOI: https://doi.org/10.1124/dmd.114.061291

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Research ArticleArticle

Fetoplacental BPA Conjugation/Deconjugation Reactions

Tanguy Corbel, Elisabeth Perdu, Véronique Gayrard, Sylvie Puel, Marlène Z. Lacroix, Catherine Viguié, Pierre-Louis Toutain, Daniel Zalko and Nicole Picard-Hagen
Drug Metabolism and Disposition April 1, 2015, 43 (4) 467-476; DOI: https://doi.org/10.1124/dmd.114.061291
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