Maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis in rats.
BACKGROUND
Maternal nicotine exposure increases lung collagen in fetal and newborn animals. Connective tissue growth factor (CTGF) plays a role in hyperoxia-induced pulmonary fibrosis.


OBJECTIVE
To determine whether pre- and postnatal nicotine exposure can augment CTGF expression and postnatal hyperoxia-induced lung fibrosis.


METHODS
Nicotine was administered to pregnant Sprague-Dawley rats at a dose of 6 mg/kg/day from gestational days 7-21 (prenatal nicotine-treated group) and gestational day 7 to postnatal day 14 (pre- and postnatal nicotine-treated group). A control group of pregnant dams was injected with an equal volume of saline. Within 12 h of birth, rats were exposed to room air or 1 week of >95% O2 and an additional 2 weeks of 60% O2 (3 weeks of hyperoxia). Lungs were taken for total collagen, CTGF expression and histological analyses.


RESULTS
In each maternal treatment group, the rats reared in hyperoxia had a higher total collagen compared with rats reared in room air on postnatal days 7 and 21. Collagen content was significantly higher in rats born to pre- and postnatal nicotine-treated dams than rats born to saline-treated and prenatal nicotine-treated dams on postnatal days 7 and 21. Pre- and postnatal nicotine exposure and neonatal hyperoxia exposure increased CTGF expression on postnatal days 7 and 21.


CONCLUSIONS
CTGF may be involved in the pathogenesis of lung fibrosis induced by maternal nicotine and neonatal hyperoxia, and maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis. These results are relevant to neonates who require supplemental oxygen and are exposed to the breast milk of smoking mothers during infancy.
Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC.
Liang-Ti
LT
Huang
Hsiu-Chu
HC
Chou
Chun-Mao
CM
Lin
Tsu-Fu
TF
Yeh
Chung-Ming
CM
Chen
D000818:Animals; D000831:Animals, Newborn; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005865:Gestational Age; D018496:Hyperoxia / Q000150:complications*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure / Q000009:adverse effects*; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D013997:Time Factors
C526316:CCN2 protein, rat; D018722:Nicotinic Agonists; D055513:Connective Tissue Growth Factor; D009538:Nicotine; D003094:Collagen