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Human Reproduction, Vol. 15, No. 12, 2483-2488, December 2000
© 2000 European Society of Human Reproduction and Embryology

Lung development following diaphragmatic hernia in the fetal rabbit

J. Wu1, H. Yamamoto1,5, E. Gratacos1,3, X. Ge1, E. Verbeken2, K. Sueishi6, S. Hashimoto6, K. Vanamo1,7, T. Lerut1,4 and J. Deprest1,3,8

1 Center for Surgical Technologies, Faculty of Medicine, Katholieke Universiteit Leuven, 2 Departments of Pathology, 3 Obstetrics & Gynaecology and 4 Thoracic Surgery, University Hospital `Gasthuisberg', Leuven, Belgium, 5 Department of Pediatric Surgery, Kumamoto University School of Medicine, Kumamoto, 6 Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka, Japan and 7 Department of Pediatric Surgery, Kuopio University Hospital, Kuopio, Finland

Diaphragmatic hernia was created in 39 rabbit fetuses on day 23 of gestation. Fifteen fetuses underwent a sham thoracotomy (SHAM). Thirty-nine non-operated littermates served as internal controls (CTR). Fetuses were harvested by Caesarean section on days 25, 27, 29 and 30 of gestation. Pulmonary response was evaluated by lung to body weight ratio (LBWR), morphometry, and density of type II pneumocytes. No difference was found between CTR and SHAM fetuses at term. CDH fetuses had smaller lungs (LBWR 0.014 ± 0.004 versus 0.030 ± 0.04 in CTR, P < 0.0001), a less complex acinus [mean terminal bronchial density (MTBD) 1.786 ± 0.408 versus 0.917 ± 0.188, P < 0.0001], thicker alveolar septa [mean wall transection length (LMW) 0.0221 ± 0.008 versus 0.0142 ± 0.002, P = 0.0003], and a lower type II cell count (144.5 ± 19.33 versus 216.2 ± 27.85 per high power field, P < 0.0001). The differences in MTBD and LMW were significant from gestational day 25 onwards, and the differences in type II cell count from day 27 onwards. Surgical diaphragmatic hernia in rabbit fetuses in the late pseudoglandular phase reproduces many features of the pulmonary hypoplasia associated with human congenital diaphragmatic hernia, including the delayed maturation. The effects are present within 2 days following experimental diaphragmatic hernia and progress over time.

Key words: animal models/congenital diaphragmatic hernia/fetal surgery/lung development/pulmonary hypoplasia

8 To whom correspondence should be addressed at: Centre for Surgical Technologies Minderbroedersstraat 17, B-3000 Leuven, Belgium. E-mail: Jan.Deprest{at}uz.kuleuven.ac.be


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