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Multigenerational epigenetic effects of nicotine on lung function
1Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA. fmleslie@uci.edu
BMC Medicine
|February 6, 2013
Summary
Maternal and grandmaternal smoking exposure increases pediatric asthma risk. Nicotine exposure in rats causes multigenerational asthma-like lung changes via epigenetic mechanisms, highlighting risks of smoking and nicotine replacement therapy in pregnancy.
Area of Science:
- Environmental Health
- Developmental Biology
- Genetics
Background:
- Maternal smoking is linked to pediatric asthma.
- A 'grandmother effect' suggests transgenerational impacts of smoking on asthma risk.
- Preclinical models are needed to investigate these multigenerational effects.
Purpose of the Study:
- To investigate the multigenerational effects of prenatal nicotine exposure on asthma-like phenotypes in rats.
- To explore the underlying epigenetic mechanisms responsible for transgenerational asthma risk.
- To assess the potential protective role of rosiglitazone against nicotine-induced effects.
Main Methods:
- Utilized a rat model with in utero nicotine exposure.
- Examined lung function and epigenetic changes (DNA and histone modifications) in offspring.
- Assessed the impact of rosiglitazone co-administration.
- Evaluated effects across two generations (F1 and F2).
Main Results:
- Nicotine exposure in pregnant rats led to asthma-like lung function changes and epigenetic alterations in F1 offspring.
- These changes were observed in both lungs and gonads of F1 offspring.
- F2 offspring, unexposed to nicotine, exhibited similar lung function changes, indicating transgenerational inheritance.
- Rosiglitazone treatment blocked the nicotine-induced alterations, suggesting peroxisome proliferator-activated receptor-γ (PPARγ) downregulation.
Conclusions:
- Epigenetic mechanisms mediate the multigenerational transmission of nicotine-induced asthma-like phenotypes.
- Findings support the 'grandmother effect' and highlight risks associated with prenatal nicotine exposure.
- Results question the safety of nicotine replacement therapy for pregnant women and emphasize smoking cessation.
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