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Prenatal Nicotine Exposure Alters Pulmonary Function in Newborn Rhesus Monkeys
Abstract
Epidemiological studies have shown that offspring of women who smoke during pregnancy have abnormal lung function and associated higher incidences of lower respiratory disorders. The recent identification of nicotinic acetylcholine receptors (nAChR) in fetal lung suggests that the direct interaction between nicotine and nAChR in fetal lung may underlie the postnatal pulmonary abnormalities seen in such infants. This hypothesis was tested in monkeys to determine if maternal nicotine exposure would produce changes in lung mechanics in newborn monkeys similar to those observed in human infants whose mothers smoked during pregnancy. Timed pregnant rhesus monkeys were infused with either nicotine (1.5 mg/kg/d, n = 7) or saline (n = 7) using subcutaneous osmotic pumps from Day 26 to 160 of gestation. On Day 160 of pregnancy (term = 165 d), fetuses were delivered by C-section, and the following day were subjected to pulmonary function testing. After testing, animals were sacrificed, and lungs weighed and fixed. Lung weight and fixed lung volume decreased (16% and 14%, respectively) significantly following in utero nicotine exposure. Peak tidal expiratory flow, FEV(0.2), mean mid-expiratory flow, forced expiratory volume at peak expiratory flow (FEV(PEF)), and FEV(PEF)/FVC% were significantly lower in newborns exposed to nicotine during gestation. Absolute and specific pulmonary resistance increased significantly whereas absolute and specific dynamic compliance remained unchanged in prenatally nicotine-treated pups. These changes in pulmonary function are strikingly similar to the changes observed in offspring of human smokers. This suggests that the interaction of nicotine with nAChR in developing lung is responsible for the altered pulmonary mechanics observed in human infants whose mothers smoked during pregnancy.
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“In both monkeys and mice, exposure to prenatal nicotine alone, at levels similar to that of smokers, causes similar decreases in forced expiratory flow.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [207]
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Metadata
- Authors
- SEKHON, H. S., KELLER, J. A., BENOWITZ, N. L., & SPINDEL, E. R.
- Affiliations
- Oregon Health & Science University (US)
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-09
- Volume
- 164
- Issue
- 6
- Pages
- 989-994
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2053834750
- Cited by
- 182
- References
- 49
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 9 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 19 · 2019: 4 · 2018: 11 · 2017: 6 · 2016: 10 · 2015: 5 · 2014: 12 · 2013: 5 · 2012: 8
- FWCI
- 6.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Center for Research Resources (RR-00163.)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD/HL-37131)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Keywords
- prenatal nicotine exposure, smoking during pregnancy, lung function, rhesus monkeys, nicotinic acetylcholine receptors, fetal lung development, lung mechanics, pulmonary resistance, lung compliance, lung weight, neonates, fetal lung
- MeSH terms
- Amniotic Fluid, Animals, Animals, Newborn, Body Weight, Chromatography, Gas, Cotinine, Data Interpretation, Statistical, Female, Fetus, Humans, Infant, Newborn, Lung, Lung Compliance, Macaca mulatta, Nicotine, Pregnancy, Respiratory Function Tests, Smoking, Mass Spectrometry
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