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| Status |
Public on Feb 02, 2017 |
| Title |
Paternal nicotine exposure alters hepatic xenobiotic metabolism in offspring |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it remains unclear whether phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a specific ligand-receptor interaction and thereby enable pharmacological interrogation of the offspring phenotype, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that paternal exposure to chronic nicotine induced a broad protective response to xenobiotic exposure in the next generation. This effect manifested as increased survival following an injection of toxic levels of nicotine, was specific to male offspring, and was only observed after these offspring were first acclimated to low levels of nicotine for a week. Importantly, offspring xenobiotic resistance was documented not only for toxic nicotine challenge, but also for toxic cocaine challenge, indicating that paternal nicotine exposure reprograms offspring to become broadly resistant to environmental toxins. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, and we found that isolated hepatocytes displayed upregulation of enzymes that metabolize xenobiotics. Taken together, our data show that paternal nicotine exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
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| Overall design |
Hepatocytes were isolated from eight week-old male F1 animals from control (TA) and nicotine-exposed fathers, 4 biological replicates each.
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| Contributor(s) |
Rando OJ, Bing XY |
| Citation(s) |
28196335 |
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| Submission date |
Dec 12, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Mike Levine |
| E-mail(s) |
msl2@princeton.edu
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| Organization name |
Princeton University
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| Department |
Lewis Sigler Institute
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| Street address |
South Dr
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| City |
Princeton |
| State/province |
NJ |
| ZIP/Postal code |
08540 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA357011 |
| SRA |
SRP094923 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE92240_RAW.tar |
1.4 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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