Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development.

Blaskovic, Sanja; Donati, Yves; Zanetti, Filippo; Ruchonnet-Métrailler, Isabelle; Lemeille, Sylvain; Cremona, Tiziana P.; Schittny, Johannes C.; Barazzone-Argiroffo, Constance (2020). Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development. American journal of physiology - lung cellular and molecular physiology, 318(4), L606-L618. American Physiological Society 10.1152/ajplung.00228.2019

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Harmful consequences of cigarette smoke (CS) exposure during lung development can already manifest in infancy. In particular, early life exposure to nicotine, the main component of CS, was shown to affect lung development in animal models. We aimed to characterize the effect of nicotine on alveoli formation. We analyzed the kinetics of normal alveolar development during the alveolarization phase and then looked at the effect of nicotine in a mouse model of gestational and early life exposure. Immunohistochemical staining revealed that the wave of cell proliferation (i.e. vascular endothelial cells, alveolar epithelial cells (AEC) type II and mesenchymal cell) occurs at pnd8 in control and nicotine-exposed lungs. However, FACS analysis of individual epithelial alveolar cells revealed nicotine-induced transient increase of AEC type I proliferation and decrease of vascular endothelial cell proliferation at pnd8. Furthermore, nicotine increased the percentage of endothelial cells at pnd2. Transcriptomic data also showed significant changes in nicotine samples compared to the controls on cell cycle associated genes at pnd2, but not anymore at pnd16. Accordingly, the expression of survivin, involved in cell cycle regulation, also follows a different kinetics in nicotine lung extracts. These changes resulted in an increased lung size detected by stereology at pnd16, but no longer in adult age, suggesting that nicotine can act on the pace of lung maturation. Taken together, our results indicate that early life nicotine exposure could be harmful to alveolar development independently from other toxicants contained in CS.

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