In recent years, a substantial research effort within the specialty of pediatric surgery has been devoted to improving our knowledge of the natural history and pathophysiology of congenital diaphragmatic hernias (CDH) and pulmonary hypoplasia (PH). However, the embryological background has remained elusive because certain events of normal diaphragmatic development were still unclear and appropriate animal models were lacking. Most authors assume that delayed or inhibited closure of the diaphragm will result in a diaphragmatic defect that is wide enough to allow herniation of the gut into the fetal thoracic cavity. However, we feel that this assumption is not based on appropriate embryological observations. To clarify whether it was correct, we restudied the morphology of pleuroperitoneal openings in normal rat embryos. Shortly before, a model for CDH and PH had been established in rats using nitrofen (2,4-di-chloro-phenyl-p-nitrophenyl ether) as teratogen. We used this model in an attempt to answer the following questions: (1) When does the diaphragmatic defect appear? (2) Are the pleuroperitoneal canals the precursors of the diaphragmatic defect? (3) Why is the lung hypoplastic in babies and infants with CDH? In our study we made following observations: (1) The typical findings of CDH and PH cannot be explained by inhibited closure of the pleuroperitoneal "canals". In normal development, the pleuroperitoneal openings are always too small to allow herniation of gut into the thoracic cavity. (2) The maldevelopment of the diaphragm starts rather early in the embryonic period (5th week). The lungs of CDH rats are significantly smaller than those of control rats at the end of the embryonic period (8th week). (3) The maldevelopment of the lungs in rats with CDH is "secondary" to the defect of the diaphragm. (4) The defect of the lungs is "structural" rather than "functional". Complete spontaneous correction of these lung defects is unlikely even after fetal intervention. (5) The "fetal lamb model" does not completely mimic the full picture of CDH, because the onset of the defect lies clearly in the fetal period. We believe that our rat model is better. It is especially useful for describing the abnormal embryology of this lesion.

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Keywords Abnormal diaphragmatic development, Congenital diaphragmatic hernia, Embryology, Nitrofen, Rat embryos
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Journal Pediatric Surgery International
Kluth, A, Tander, B, von Ekesparre, M, Tibboel, D, & Lambrecht, W. (1995). Congenital diaphragmatic hernia: the impact of embryological studies. Pediatric Surgery International, 10(1), 16–22. doi:10.1007/BF00174435