Structural analysis of fetal rat lung development.

The primary aim of this morphological investigation was to elaborate a concept allowing us to coherently define reference spaces for morphometric analysis of fetal lung development. Beyond this quantitative goal, morphological analysis of cell types, definition of compartments, and reflection about the prospective fate of their constituents provided per se new insights into the developmental processes. Lungs of rat fetuses aged 17-23 days and newborns aged 20 hours were fixed with an osmium tetroxide and glutaraldehyde mixture and their volume determined. Left lungs were embedded in Epon and investigated by light and electron microscopy. The right lung of one animal per group was embedded in methacrylate and step sections obtained to precisely locate the airways within the mesenchyme. The various cell types, their topographical relationships, and their morphological alterations with ongoing development were analyzed with regard to their prospective potentials of differentiation. The developing lung could be partitioned into four zones further subdivided into defined compartments. Zone I forms a superficial mantle around the lobes and the future acini. Consisting of primitive mesenchymal cells, it represents a zone of growth which disappears with the onset of the saccular stage. Zone II is mainly a zone of differentiation. Its interstitium stains intensely due to a dense population of dark cells. Up to gestational day 19, zone II contains future conductive airways with their vessels. After day 21, it comprises the whole prospective gas exchange region. Zones III and IV contain the elements of the airway tree and vascular system, zone IV corresponding to the most proximal generations with an adventitial layer. For all differentiation processes, a centrifugal directionality is manifested.