Academic journal article Environmental Health Perspectives

Combined Effects of in Utero and Adolescent Tobacco Smoke Exposure on Lung Function in C57BL/6J Mice

Academic journal article Environmental Health Perspectives

Combined Effects of in Utero and Adolescent Tobacco Smoke Exposure on Lung Function in C57BL/6J Mice

Article excerpt


Chronic obstructive pulmonary disease (COPD) is a major cause of death and disability worldwide that is expected to increase in prevalence over the next few years (Lopez et al. 2006). A better understanding of the conditions leading to its occurrence is required to facilitate its prevention. Smoking is the main risk factor for COPD, but only a minority of smokers develop the disease (Chen et al. 2010), and nonsmokers account for a substantive part of the burden of COPD (Eisner et al. 2010). Thus, both environmental exposure and individual susceptibility factors are involved in the pathogenesis and progression of COPD.

The quality of lung development is known to play a critical role in determining pulmonary function in adults (Boucherat et al. 2016; Rennard and Drummond 2015). Previous findings suggest that the maximum lung function attained after childhood lung growth is a key determinant of the rate of functional decline leading to a COPD diagnosis (Lange et al. 2015; Rennard and Drummond 2015). Prenatal airway growth may be a key predictor of adult lung function. For example, poor airway function measured shortly after birth in 123 infants predicted airflow obstruction in early adulthood (Stern et al. 2007). A systematic review and meta-analysis by Kotecha et al. (2013) indicated that premature birth, which interrupts physiological prenatal growth, is negatively associated with later pulmonary function in children and adults. Finally, genes involved in early airway morphogenesis have been associated with lung function and COPD (Klar et al. 2011; Van Durme et al. 2010). The impairment of prenatal airway growth may be related to exposure to environmental factors, such as in utero exposure to maternal cigarette smoke (CS). Exposure to maternal CS has been negatively associated with lung function in adolescents and young adults (Hollams et al. 2014) and in early adulthood (Hayatbakhsh et al. 2009). One key question concerns the potential role of preexisting airway obstruction, secondary to impaired prenatal growth, as a risk factor for an earlier onset or more rapid decline in lung function in individuals beginning to smoke actively during adolescence or early adulthood. Previous studies have suggested that maternal smoking and personal smoking may have a synergistic effect on lung function decline, but these studies were unable to separate the influences of prenatal and postnatal exposure to parental smoking (Guerra et al. 2013; Upton et al. 2004).

In this study, we used a murine model to investigate whether in utero exposure to CS caused an accelerated decline in lung function in mice that were also exposed to CS during adolescence.

Our secondary objective was to determine whether the combined effects of in utero exposure and exposure during adolescence to CS led to an acceleration of lung senescence. Several studies have suggested that the aging process is accelerated in the development of COPD (Ito and Barnes 2009). Prebronchodilator forced expiratory volume in the first second (FEV1) values were positively associated with telomere length in peripheral leukocytes, a biomarker of cell senescence, in a combined analysis of 14 European cohorts (Albrecht et al. 2014).



All of the animal experiments were approved by the local institutional animal care and use committee (Agreement number 11/11/15-4), and all animals were treated humanely and with regard for alleviation of suffering. Twelve-week-old female C57Bl/6J mice were obtained from Janvier (France), housed in groups of 4, and given 1 week to acclimate to the housing facility. Environmental conditions were a temperature of 21[degrees]C, humidity of 55%, lighting of 300 lux (at bench level) and a 12:12 light:dark cycle with lights on at 0800 hours and off at 2000 hours. Animals were housed in 330 mm x 150 mm x 130 mm cages and given access to mouse maintenance food (reference A03. …

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