Multigenerational epigenetic effects of nicotine on lung function

BMC Medicine

Frances M Leslie¹ 

[1]Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697, USA

关键词: tobacco;    smoking;    peroxisome proliferator-activated receptor-γ (PPARγ);    nicotine replacement therapy (NRT);    histone acetylation;    DNA methylation;    development;   

Others  :  857205
DOI  :  10.1186/1741-7015-11-27

 received in 2012-11-30, accepted in 2013-02-04,  发布年份 2013

【 摘 要 】

A recent preclinical study has shown that not only maternal smoking but also grandmaternal smoking is associated with elevated pediatric asthma risk. Using a well-established rat model of in utero nicotine exposure, Rehan et al. have now demonstrated multigenerational effects of nicotine that could explain this 'grandmother effect'. F1 offspring of nicotine-treated pregnant rats exhibited asthma-like changes to lung function and associated epigenetic changes to DNA and histones in both lungs and gonads. These alterations were blocked by co-administration of the peroxisome proliferator-activated receptor-γ agonist, rosiglitazone, implicating downregulation of this receptor in the nicotine effects. F2 offspring of F1 mated animals exhibited similar changes in lung function to that of their parents, even though they had never been exposed to nicotine. Thus epigenetic mechanisms appear to underlie the multigenerational transmission of a nicotine-induced asthma-like phenotype. These findings emphasize the need for more effective smoking cessation strategies during pregnancy, and cast further doubt on the safety of using nicotine replacement therapy to reduce tobacco use in pregnant women.

Please see related article: http://www.biomedcentral.com/1741-7015/10/129 webcite

【 授权许可】

   
2013 Leslie; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

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