Maternal Nicotine Exposure Exacerbates Neonatal Hyperoxia-Induced Lung Fibrosis in Rats

Abstract

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.

Maternal Nicotine Exposure Induces Epithelial-Mesenchymal Transition in Rat Offspring Lungs

“…Myofibroblasts are differentiated fibroblasts that possess contractile properties similar to those of smooth muscle cells, and they are characterized by the presence of α-SMA. EMT has been categorized based on the physiological context into 3 distinct types: developmental, fibrosis and wound healing, and cancer [12]. Epithelial cells express high E-cadherin levels, whereas mesenchymal cells express high N-cadherin and FSP-1 levels [24].…”

“…There exists a vast amount of literature describing the mechanisms of smoking- and nicotine-induced lung fibrosis [10,11]. We recently demonstrated that maternal nicotine exposure induces lung injuries and fibrosis, which is shown by increased inflammatory cell recruitment and collagen synthesis in the lungs of rat offspring [12]. Epithelial-mesenchymal transition (EMT) following lung injury is a process in which epithelial cells lose their cell polarity and cell-cell adhesion features and gain migratory properties to become mesenchymal (fibroblast-like) cells [13].…”

Maternal nicotine exposure during gestation and lactation induces kidney injury and fibrosis in rat offspring

“…The kidney tissues used for these experiments were obtained from a previous study designed to assess lung fibrosis (36). All rats described in the present manuscript were kept at room air and were not exposed to 95%/60% O 2 .…”

Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

“…Neonatal hyperoxia-induced lung injury serves as an excellent model for mechanistic studies to better understand how hyperoxia disrupts lung development and for preclinical testing of potential therapies for BPD. “Two hit” models have combined postnatal hyperoxia with antenatal lipopolysaccharide (LPS) to represent perinatal inflammation, such as chorioamnionitis [34, 35]; hyperoxia and maternal nicotine administration [36] and hyperoxia with intermittent hypoxia to represent combined injuries [37-39] in the pathogenesis of experimental BPD.…”