Chronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow obstruction, accompanied by the progressive loss of lung function. COPD clinical onset occurs after 40ys, but the role of events occurring before entering adult life is more and more suggested. As exposure of adults or children to air pollution is associated with (functional) respiratory alterations, and perinatal exposure to air pollution has been reported to cause deleterious consequences on fetal growth and development, our hypothesis is that prenatal exposure to air pollution could represent a susceptibility factor to develop COPD at adult age. Our objective is therefore to address this issue thanks to an innovative approach based on the use of an atmospheric simulation chamber dedicated to the study of multiphasic atmospheric processes.
Pregnant C57/BL6J mice were exposed to Beijing- or Paris-type atmospheres (hereafter: Beijing or Paris) or to their respective Control air from 9th to 16th day of gestation. At adulthood (D60), the offspring are exposed to cigarette smoke, as a mice model of COPD. The effects on lung development, remodeling and function in the offspring were studied at different life stages. The kinetics of appearance of COPD and its severity were analyzed.
Prenatal exposure to either Beijing or Paris simulated atmosphere is accompanied by a higher neonatal mortality as compared to their respective Control air. At adolescence (D17), morphological analyses show a delayed lung development in Beijing offspring as compared to its Control air. Interestingly, the lung of offspring “catches up” at adult age (D60), as a normal pulmonary structure is observed. After 3-month cigarette smoking (D150), we can observe a destruction of alveolar walls in Beijing offspring (characteristic of emphysema), as well as in their littermates exposed in utero to Control air. No such phenomena are observed in Paris offspring. The underlying molecular mechanisms are still under investigation.
Prenatal exposure to high pollution simulated atmosphere leads to a delayed pulmonary development, followed by a catch-up at adult age. At the moment, our results do not allow us to state that this leads to a particular susceptibility to develop COPD later on.Le texte complet de cet article est disponible en PDF.
Keyword : COPD