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Author Notes:

Correspondence and requests for reprints should be addressed to Cherry Wongtrakool, M.D., Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA 30033. E-mail: cwongtr@emory.edu

The authors sincerely thank Susanne Roser-Page and Kora Grooms for excellent technical assistance, specifically immunohistochemistry and animal care, Judy St. George for assisting in airway measurements, and Xiaowei Yang for assisting in the statistical analysis. They also thank Art Beaudet for assistance with the α7 nicotinic acetylcholine receptor knockout mice.


Research Funding:

This work was supported by National Institutes of Health (NIH) grants HL080293 (C.W.), NIH RR00163 (E.R.S.), NIH HL066118 (E.R.S.), and by the American Thoracic Society Research Program (C.W.) and a Veterans Affairs Merit Review (J.R.).


  • lung development
  • nicotine
  • branching

Prenatal Nicotine Exposure Alters Lung Function and Airway Geometry through α7 Nicotinic Receptors


Journal Title:

American Journal of Respiratory Cell and Molecular Biology


Volume 46, Number 5


, Pages 695-702

Type of Work:

Article | Post-print: After Peer Review


Maternal smoking during pregnancy has been associated with adverse effects on respiratory health. Whereas the epidemiologic link is incontrovertible, the mechanisms responsible for this association are still poorly understood. Although cigarette smoke has many toxic constituents, nicotine, the major addictive component in cigarette smoke, may play a more significant role than previously realized. The objectives of this study were to determine whether exposure to nicotine prenatally leads to alterations in pulmonary function and airway geometry in offspring, and whether α7 nicotinic acetylcholine receptors (nAChRs) mediate these effects. In a murine model of in utero nicotine exposure, pulmonary function, airway size and number, methacholine response, and collagen deposition were examined. Exposure periods included Gestation Days 7–21, Gestation Day 14 to Postnatal Day 7, and Postnatal Days 3–15. Prenatal nicotine exposure decreases forced expiratory flows in offspring through α7 nAChR–mediated signals, and the critical period of nicotine exposure was between Prenatal Day 14 and Postnatal Day 7. These physiologic changes were associated with increased airway length and decreased diameter. In addition, adult mice exposed to prenatal nicotine exhibit an increased response to methacholine challenge, even in the absence of allergic sensitization. Collagen expression was increased between adjacent airways and vessels, which was absent in α7 nAChR knockout mice. These observations provide a unified mechanism of how maternal smoking during pregnancy may lead to lifelong alterations in offspring pulmonary function and increased risk of asthma, and suggest potential targets to counteract those effects.

Copyright information:

Copyright © 2012 by the American Thoracic Society

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