Tracheal occlusion in the fetal rat: A new experimental model for the study of accelerated lung growth

Abstract Background: Prenatal tracheal occlusion accelerates fetal lung growth, but the mechanism of this phenomenon is unknown. Previous animal models have been limited by expense, lack of species-specific molecular probes, or the stage of lung development when studies could be performed. To provide a model that is more amenable to systematic analysis, we have developed an in vivo rat model of prenatal tracheal occlusion. Methods: Time-dated pregnant rats underwent laparotomy at 19 days' gestational age (term, 22 days). The fetal head and neck were exteriorized through a hysterotomy, and the trachea was ligated under a dissecting microscope. The fetus was returned to the amniotic cavity, and the uterine and maternal abdominal incisions were closed. The dam and the fetuses were killed at 21.5 days' gestational age, and the fetal lungs were assessed for lung growth and compared with nonoperated littermate controls. Results: Thirty-two of 50 manipulated fetuses survived. Of the 32 survivors, successful tracheal, ligation was confirmed in 20, and these 20 fetuses were compared with 33 littermate controls. Fetal body weight (4.81 ± 0.26 g v 4.87 ± 0.41 g) and heart weight (0.05 ± 0.01 g v 0.05 ± 0.01 g) were not significantly different between ligated fetuses and littermate controls, whereas the wet lung weight (0.30 ± 0.06 g v 0.13 ± 0.02 g, P v 2.64 ± 0.41%, P v 12.1 ± 1.87 mg, P v 828 ± 208 μg, P v 8.7 ± 1.7 mg, P Conclusions: Prenatal tracheal occlusion during the canalicular stage of lung development accelerates lung growth in the rat. In comparison with other large animal models, this relatively inexpensive small animal model has the distinct advantages of a short gestation, a large number of fetuses per litter, the availability of a developmental model of congenital diaphragmatic hernia, and the availability of well-defined molecular probes to investigate the mechanism of tracheal occlusion-induced lung growth.