1. Chromosomes and Gene Expression
Download icon

Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring

  1. Markus P Vallaster
  2. Shweta Kukreja
  3. Xinyang Y Bing
  4. Jennifer Ngolab
  5. Rubing Zhao-Shea
  6. Paul D Gardner
  7. Andrew R Tapper  Is a corresponding author
  8. Oliver J Rando  Is a corresponding author
  1. University of Massachusetts Medical School, United States
Research Article
  • Cited 14
  • Views 2,224
  • Annotations
Cite this article as: eLife 2017;6:e24771 doi: 10.7554/eLife.24771

Abstract

Paternal environmental conditions can influence phenotypes in future generations, but it is unclear whether offspring phenotypes represent specific responses to particular aspects of the paternal exposure history, or a generic response to paternal 'quality of life'. Here, we establish a paternal effect model based on nicotine exposure in mice, enabling pharmacological interrogation of the specificity of the offspring response. Paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in male offspring. This effect manifested as increased survival following injection of toxic levels of either nicotine or cocaine, accompanied by hepatic upregulation of xenobiotic processing genes, and enhanced drug clearance. Surprisingly, this protective effect could also be induced by a nicotinic receptor antagonist, suggesting that xenobiotic exposure, rather than nicotinic receptor signaling, is responsible for programming offspring drug resistance. Thus, paternal drug exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics.

Article and author information

Author details

  1. Markus P Vallaster

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Shweta Kukreja

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xinyang Y Bing

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer Ngolab

    Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Rubing Zhao-Shea

    Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul D Gardner

    Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Andrew R Tapper

    Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Andrew.Tapper@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Oliver J Rando

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    Oliver.Rando@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1516-9397

Funding

National Institute on Drug Abuse

  • Markus P Vallaster
  • Jennifer Ngolab
  • Rubing Zhao-Shea
  • Paul D Gardner
  • Andrew R Tapper
  • Oliver J Rando

Eunice Kennedy Shriver National Institute of Child Health and Human Development

  • Shweta Kukreja
  • Xinyang Y Bing
  • Oliver J Rando

National Institutes of Health (F32DA034414)

  • Markus P Vallaster

National Institutes of Health (R01DA033664)

  • Paul D Gardner
  • Andrew R Tapper
  • Oliver J Rando

National Institutes of Health (R01HD080224)

  • Oliver J Rando

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol (A-1788) of the University of Massachusetts.

Reviewing Editor

  1. Detlef Weigel, Max Planck Institute for Developmental Biology, Germany

Publication history

  1. Received: December 30, 2016
  2. Accepted: January 31, 2017
  3. Accepted Manuscript published: February 14, 2017 (version 1)
  4. Version of Record published: March 7, 2017 (version 2)

Copyright

© 2017, Vallaster et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,224
    Page views
  • 541
    Downloads
  • 14
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

  1. Exposing male mice to nicotine can make their sons more resistant to nicotine and other drugs.

    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression
    Kanokwan Champasa et al.
    Research Article Updated