Me. Depaepe et al., TEMPORAL PATTERN OF ACCELERATED LUNG GROWTH AFTER TRACHEAL OCCLUSION IN THE FETAL RABBIT, The American journal of pathology, 152(1), 1998, pp. 179-190
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.