Genomics

Dataset Information

0

Intergenerational programming of hepatic xenobiotic response by paternal Nicotine exposure


ABSTRACT: Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it generally remains unclear whether the 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 known ligand-receptor interaction and thereby enable pharmacological interrogation of the specificity of the offspring response, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that chronic paternal exposure to nicotine prior to reproduction induced a broad protective response to multiple xenobiotics in the next generation. This effect manifested as increased survival following an injection of toxic levels of either nicotine or of cocaine, was specific to male offspring, and was only observed after offspring were first acclimated to sublethal doses of nicotine or cocaine. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, accompanied by hepatic upregulation of genes involved in xenobiotic metabolism. Surprisingly, this protective effect could also be induced by paternal exposure to a nicotinic receptor antagonist as well as to nicotine, suggesting that paternal xenobiotic exposure, rather than nicotinic receptor signaling, is likely to be responsible for programming of offspring drug resistance. Taken together, our data show that paternal drug exposure can induce a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.

ORGANISM(S): Mus musculus

PROVIDER: GSE94059 | GEO | 2017/02/01

SECONDARY ACCESSION(S): PRJNA368689

REPOSITORIES: GEO

Similar Datasets

2017-02-02 | GSE92240 | GEO
| PRJNA357011 | ENA
2022-04-01 | GSE199661 | GEO
2020-07-31 | GSE155308 | GEO
2019-11-25 | GSE140904 | GEO
2019-11-25 | GSE140903 | GEO
| PRJNA649278 | ENA
| PRJNA368689 | ENA
2008-04-19 | GSE11208 | GEO
| E-GEOD-11208 | biostudies-arrayexpress