Developmental nicotine exposure results in programming of alveolar simplification and interstitial pulmonary fibrosis in adult male rats.

AIMS: 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.