Structure of the primordial diaphragm and defects associated with nitrofen-induced CDH

The goals of this study were to further our understanding of diaphragm embr yogenesis and the pathogenesis of congenital diaphragmatic hernia (CDH). Pa st work suggests that the pleuroperitoneal fold (PPF) is the primary source of diaphragmatic musculature. Furthermore, defects associated with an anim al model of CDH can be traced back to the formation of the PPF. This study was designed to elucidate the anatomic structure of the PPF and to determin e which regions of the PPF malform in the well-established nitrofen model o f CDH. This was achieved by producing three-dimensional renderings construc ted from serial transverse sections of control and nitrofen-exposed rats at embryonic day 13.5. Renderings of left-and right-sided defects demonstrate d that the malformations were always limited to the dorsolateral portions o f the caudal regions of the PPF. These data provide an explanation of why t he holes in diaphragmatic musculature associated with CDH are characteristi cally located in dorsolateral regions. Moreover, these data provide further evidence against the widely stated hypothesis that a failure of pleuroperi toneal canal closure underlies the pathogenesis of nitrofen-induced CDH.