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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Alteration of the Expression of Pesticide-Metabolizing Enzymes in Pregnant Mice: Potential Role in the Increased Vulnerability of the Developing Brain

Marie C. Fortin, Lauren M. Aleksunes and Jason R. Richardson
Drug Metabolism and Disposition February 2013, 41 (2) 326-331; DOI: https://doi.org/10.1124/dmd.112.049395
Marie C. Fortin
Environmental and Occupational Health Sciences Institute, A Joint Institute of Rutgers University and the University of Medicine and Dentistry of New Jersey (M.C.F., L.M.A., J.R.R.), Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School (J.R.R.), Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University (L.M.A.), Piscataway, New Jersey
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Lauren M. Aleksunes
Environmental and Occupational Health Sciences Institute, A Joint Institute of Rutgers University and the University of Medicine and Dentistry of New Jersey (M.C.F., L.M.A., J.R.R.), Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School (J.R.R.), Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University (L.M.A.), Piscataway, New Jersey
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Jason R. Richardson
Environmental and Occupational Health Sciences Institute, A Joint Institute of Rutgers University and the University of Medicine and Dentistry of New Jersey (M.C.F., L.M.A., J.R.R.), Department of Environmental and Occupational Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School (J.R.R.), Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University (L.M.A.), Piscataway, New Jersey
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Abstract

Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy. However, it is not known whether pesticide metabolic capacity changes throughout pregnancy, which could affect exposure of the developing brain. We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides. Livers were collected from virgin and pregnant C57BL/6 mice at gestational days (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA expression of several enzymes involved in the metabolism of pesticides, including hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 (Pon1), were assessed in mice during gestation and the postpartum period. Compared with virgin mice, alterations in the expression occurred at multiple time points, with the largest changes observed on GD14. At this time point, the expression of most of the Cyps involved in pesticide metabolism in the liver (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 30% or more. Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity. These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy, which could alter exposure of developing animals to these chemicals.

Footnotes

  • This work was supported in part by National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK080774] and National Institutes of Health National Institute of Environmental Health Sciences [Grants ES015991, ES020522, ES007148, and ES005022].The content of this manuscript does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institute of Environmental Health Sciences.

  • dx.doi.org/10.1124/dmd.112.049395

  • ↵Embedded ImageThis article contains supplemental material available at dmd.aspetjournals.org.

  • Received October 3, 2012.
  • Accepted December 4, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 41 (2)
Drug Metabolism and Disposition
Vol. 41, Issue 2
1 Feb 2013
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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Pesticide-Metabolizing Enzymes in Pregnancy

Marie C. Fortin, Lauren M. Aleksunes and Jason R. Richardson
Drug Metabolism and Disposition February 1, 2013, 41 (2) 326-331; DOI: https://doi.org/10.1124/dmd.112.049395

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Rapid CommunicationSpecial Section on Drug Metabolizing Enzymes and Transporters in Pregnancy

Pesticide-Metabolizing Enzymes in Pregnancy

Marie C. Fortin, Lauren M. Aleksunes and Jason R. Richardson
Drug Metabolism and Disposition February 1, 2013, 41 (2) 326-331; DOI: https://doi.org/10.1124/dmd.112.049395
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  • Increased Cyp2d and Cyp26a1 During Mouse Pregnancy
  • CYP Regulation by Female Hormones
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