Developmental nicotine exposure results in programming of alveolar simplification and interstitial pulmonary fibrosis in adult male rats.
OBJECTIVE
To determine the long-term effect of maternal nicotine intake on the lung development of the offspring in adult life, we analyzed the alveolar structure, protein expression in the adult rat offspring lungs.


METHODS
We determined animal body weight (BW), lung weight (LW), lung/body weight ratio (L/BWR), lung volume (LV), radial alveolar count (RAC), alveolar septal thickness (AST) and expression of collagen, AT1R, AT2R, TGF-β1, pSmad3, Smad3 and CTGF proteins.


RESULTS
Male offspring lung showed decreased RAC, thickened alveolar septa, increased collagen, AT1R, TGF-β1, pSmad3 and CTGF proteins. In contrast, female offspring lungs had reduced L/BWR, increased LV, and expression of AT2R, resulting in decreased AT1R to AT2R ratio.


CONCLUSIONS
Maternal nicotine use during development programs abnormal lung development in male rats. This finding links maternal nicotine use to increased susceptibility to interstitial pulmonary fibrosis in adult male but not female offspring, indicating sex-dependent effects of developmental nicotine exposure.
Institute for Fetal Origin Diseases, First Hospital of Soochow University and Prenatal Biology, Center of Soochow University, Suzhou, China. cdasgupta@llu.edu
Chiranjib
C
Dasgupta
DaLiao
D
Xiao
Zhice
Z
Xu
Shumei
S
Yang
Lubo
L
Zhang
D000818:Animals; D003094:Collagen / Q000378:metabolism; D005260:Female; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008431:Maternal-Fetal Exchange; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D018722:Nicotinic Agonists; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D053773:Transforming Growth Factor beta1; D009538:Nicotine; D003094:Collagen