Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring
AuthorsVallaster, Markus P.
Bing, Xin Y.
Gardner, Paul D.
Tapper, Andrew R.
Rando, Oliver J.
Student AuthorsJennifer Ngolab
UMass Chan AffiliationsGardner Lab
Graduate School of Biomedical Sciences, Neuroscience Program
Brudnick Neuropsychiatric Research Institute
Department of Psychiatry
Department of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
Cell and Developmental Biology
Neuroscience and Neurobiology
Substance Abuse and Addiction
MetadataShow full item record
AbstractPaternal 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.
Elife. 2017 Feb 14;6. pii: e24771. doi: 10.7554/eLife.24771. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/46217
Co-author Jennifer Ngolab is a doctoral student in the Neuroscience Program in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
RightsCopyright © 2017, Vallaster et al.
Except where otherwise noted, this item's license is described as Copyright © 2017, Vallaster et al.