Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels
Open accessAbstract
Among the many deleterious effects of maternal smoking during pregnancy on foetal development, is a higher incidence of persistent pulmonary hypertension. The recent identification of nicotinic acetylcholine receptors (nAChR) on cells of the pulmonary vessel walls suggests that maternal smoking during pregnancy may produce morphological alterations in foetal pulmonary vasculature. Timedpregnant rhesus monkeys were treated with nicotine (1 mg·kg−1·day−1) delivered by subcutaneous osmotic minipumps from days 26–134 of gestation (term: 165 days). Lung sections from 134‐day foetal monkeys were used for morphometric analysis,in situ hybridisation and immunohistochemical staining. Following nicotine treatment, total wall and tunica adventitia thickness of airway associated vessels (AAV) increased significantly. Nicotine exposure significantly increased collagen I and III mRNA and protein in tunica adventitia in all AAV but not in tunica media. By contrast, levels of elastin protein were significantly decreased. α7 nAChR were detected in AAV fibroblasts that expressed collagen mRNA. Choline acetyltransferase, the enzyme which synthesises acetylcholine, the ligand for α7 nAChR was also detected in endothelium and fibroblasts. These findings suggest that with smoking during pregnancy, nicotine is transported across the placenta and directly interacts with nicotinic acetylcholine receptors in pulmonary vessels to alter connective tissue expression and therefore produce vascular structural alterations.
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Treating pregnant rhesus monkeys with nicotine causes marked increases of α7 nAChR in fibroblasts around fetal lung airways and blood vessels and increases collagen in a similar distribution.
“Treatment of pregnant rhesus monkeys with nicotine causes marked increases of levels of α7 nAChR in fibroblasts surrounding airways and blood vessels in the fetal monkey lung, and increases in collagen in a similar distribution.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [210]
Prenatal nicotine exposure thickens airway and pulmonary vessel walls in animal models, and this finding has also been reported in human offspring of smokers.
“Prenatal nicotine exposure leads to thickening of walls surrounding airways and pulmonary vessels in animal models,(209, 210) a finding that has also been reported in the human offspring of smokers,(211, 212) along with similar increases in connective tissue and α7 expression.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [210]
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- Authors
- Sekhon, H. S., Proskocil, B. J., Clark, J. A., & Spindel, E. R.
- Affiliations
- Oregon National Primate Research Center (US)
- Oregon Health & Science University (US)
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2004-06
- Volume
- 23
- Issue
- 6
- Pages
- 906-915
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- OpenAlex
- W2043435839
- Cited by
- 81
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 8 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 10
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Respiratory Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Oregon National Primate Research Center
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Neonatal Respiratory Health Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- prenatal nicotine exposure, smoking during pregnancy, persistent pulmonary hypertension of the newborn, pulmonary vasculature, connective tissue, collagen I and III, elastin, alpha7 nicotinic acetylcholine receptor, choline acetyltransferase, rhesus monkey fetus
- MeSH terms
- Animals, Bungarotoxins, Connective Tissue, Female, Embryonic and Fetal Development, Immunohistochemistry, Lung, Macaca mulatta, Nicotine, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Smoking, In Situ Hybridization
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