TEMPORAL PATTERN OF ACCELERATED LUNG GROWTH AFTER TRACHEAL OCCLUSION IN THE FETAL RABBIT

Tracheal occlusion in utero is a potent stimulus of fetal lung growth. We describe the early growth mechanics of fetal lungs and type II pne umocytes after tracheal ligation (TL). Fetal rabbits underwent TL at 2 4 days gestational age (DGA; late pseudoglandular stage; term = 31 to 33 days) and were sacrificed at time intervals ranging from 1 to 5 day s after TL. Lung growth was measured by stereological volumetry and br omodeoxyuridine (BrdU) pulse labeling, Pneumocyte II population kineti cs were analyzed using a combination of anti-surfactant protein A and BrdU immunohistochemistry and computer-assisted morphometry. Nonoperat ed littermates served as controls. TL resulted in dramatically enhance d lung growth (lung weight/body weight was 5.00 +/- 0.81% in TL versus 2.52 +/- 0.13% in controls at 29 DGA; P < 0.001, unpaired Student's t -test), Post-TL lung growth was characterized by a 3-day lag-phase typ ified by relative stagnation of growth, followed by distension of airs paces, increased cell proliferation, and accelerated architectural and cellular maturation by post-ligation days 4 and 5. During the prolife ration phase, the replicative activity of type II cells was markedly i ncreased (type II cell BrdU labeling index was 10.0 +/- 4.1% in TL ver sus 1.1 +/- 0.3% for controls at 29 DGA; P < 0.02), but their numerica l density decreased (3.0 +/- 0.5 x 10(-3)/mu m(2) in TL versus 4.5 +/- 0.3 x 10(-3)/mu m(2) in controls at 29 DGA; P < 0.02), suggesting acc elerated terminal differentiation to type I cells. In conclusion, post -TL lung development is characterized by a well defined temporal patte rn of lung growth and maturation, The rabbit model lends itself well t o study the regulatory mechanisms underlying accelerated fetal lung gr owth after TL.