Perinatal exposure to environmental tobacco smoke is associated with changes in DNA methylation that precede the adult onset of lung disease in a mouse model

Abstract

Prenatal and early-life environmental tobacco smoke (ETS) exposure can induce epigenetic alterations associated with inflammation and respiratory disease. The objective of this study was to address the long-term epigenetic consequences of perinatal ETS exposure on latent respiratory disease risk, which are still largely unknown. C57BL/6 mice were exposed to prenatal and early-life ETS; offspring lung pathology, global DNA, and gene-specific methylation were measured at two adult ages. Significant alterations in global DNA methylation and promoter methylation of IFN-γ and Thy-1 were found in ETS-exposed offspring at 10–12 and 20 weeks of age. These sustained epigenetic alterations preceded the onset of significant pulmonary pathologies observed at 20 weeks of age. This study suggests that perinatal ETS exposure induces persistent epigenetic alterations in global DNA, as well as IFN-γ and Thy-1 promoter methylation that precede the adult onset of fibrotic lung pathology. These epigenetic findings could represent potential biomarkers of latent respiratory disease risk.

Keywords:

• Inflammation
• early life
• environmental tobacco smoke
• methylation
• prenatal
• respiratory disease

Acknowledgments

The authors thank Virginia Porter, Mary Buford, Melisa Schelvan, Forrest Jessop, Pamela Shaw, Lou Herritt, Zeina Jaffar, Maria Ferrini, the Fluorescence Cytometry Core, and the Molecular Histology and Fluorescence Imaging Core (Center for Environmental Health Sciences at UM), Dale Uyeminami, and Shanie McCarty (Center for Health and the Environment at the University of California, Davis) for their varied expert technical assistance with different aspects of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health [grant number P30GM103338] and an S10 Shared Instrument Grant [grant number S10RR026325-01]. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NIGMS or NIEHS.