Stereological monitoring of mouse lung alveolarization from the early postnatal period to adulthood.
Postnatal lung maturation generates a large number of small alveoli, with concomitant thinning of alveolar septal walls, generating a large gas exchange surface area but minimizing the distance traversed by the gases. This demand for a large and thin gas exchange surface area is not met in disorders of lung development, such as bronchopulmonary dysplasia (BPD) histopathologically characterized by fewer, larger alveoli and thickened alveolar septal walls. Diseases such as BPD are often modeled in the laboratory mouse to better understand disease pathogenesis or to develop new interventional approaches. To date, there have been no stereology-based longitudinal studies on postnatal mouse lung development that report dynamic changes in alveoli number or alveolar septal wall thickness during lung maturation. To this end, changes in lung structure were quantified over the first 22 mo of postnatal life of C57BL/6J mice. Alveolar density peaked at postnatal day (P)39 and remained unchanged at 9 mo (P274) but was reduced by 22 mo (P669). Alveoli continued to be generated, initially at an accelerated rate between P5 and P14, and at a slower rate thereafter. Between P274 and P669, loss of alveoli was noted, without any reduction in lung volume. A progressive thinning of the alveolar septal wall was noted between P5 and P28. Pronounced sex differences were observed in alveoli number in adult (but not juvenile) mice, when comparing male and female mouse lungs. This sex difference was attributed exclusively to the larger volume of male mouse lungs.
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Agnieszka
A
Pozarska
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
José Alberto
JA
Rodríguez-Castillo
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
David E
DE
Surate Solaligue
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Aglaia
A
Ntokou
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.
Philipp
P
Rath
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Ivana
I
Mižíková
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Alicia
A
Madurga
Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Konstantin
K
Mayer
Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
István
I
Vadász
Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Susanne
S
Herold
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Katrin
K
Ahlbrecht
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Werner
W
Seeger
Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany; and rory.morty@mpi-bn.mpg.de.|Department of Internal Medicine (Pulmonology), University of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Giessen, Germany.
Rory E
RE
Morty
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009929:Organ Size; D011650:Pulmonary Alveoli / Q000033:anatomy & histology / Q000254:growth & development*; D012727:Sex Characteristics