Embryology of congenital diaphragmatic hernia.

It is still generally believed that the defect in congenital diaphragmatic hernia results from failure of the so-called pleuroperitoneal canals (PPCs) to close at the end of the embryonic period (8th gestational week). Furthermore, it is assumed that gut could enter the thoracic cavity through this defect, causing compression and finally hypoplasia of the lung. However, this sequence of embryological events has never been studied, and many details even of normal diaphragmatic development are still unknown. Using scanning electron microscopy and a new animal model of congenital diaphragmatic hernia (CDH), the nitrofen rat model, the normal embryology of the diaphragm was reinvestigated and, for the first time, the crucial developmental steps of congenital diaphragmatic hernia formation were studied. The basic results were: (1) In normal development, the PPCs are never wide enough to allow herniation of gut loops. (2) The formation of the defect happens in an early embryonic period. (3) The early ingrowth of liver through the defect is of major importance for the formation of CDH. In another set of experiments, the nitrofen rat model of congenital diaphragmatic hernias was used to study the cellular mechanisms involved during epithelial and mesenchymal growth and differentiation in normal and in abnormal lungs. These results, combined with selected culture techniques (eg, branching morphogenesis and epithelio-mesenchymal interaction) probably open new ways to a better understanding of the mechanisms that finally lead to an abnormal lung in CDH.