Structural analysis of fetal rat lung development

Abstract

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.

Effects of oligohydramnios on lung growth and maturation in the fetal rat

“…These effects included reduced expression of RTI 40 mRNA and its protein as well as diminished surface coverage by type I cells compared with type II cells in the distal potential air spaces. The effects of oligohydramnios on epithelial differentiation, although apparent at 21 days, were more pronounced at 22 days, a time when the prospective air spaces of the fetal rat lung are undergoing dilatation (9).…”

Developmental Implications

“…In RFL at Embryonic Day 16, PARP-1 was expressed mainly in peripheral lung parenchyma and in epithelial tubules, regions associated with cell proliferation in pseudoglandular lung (36), as well as dividing cells (Figure 4A), findings consistent with previous observations in vitro of upregulation of PARP-1 in dividing cells (9). In proliferating acute promyelocytic leukemia cells PARP-1 regulates cell cycle progression (6).…”

“…This apparent conflict with the data in Figure 1 Immunolocalization showed that PARP-1 expression became progressively more restricted with maturation, so that fewer cells expressed PARP-1, whereas those that continued to express it did so at relatively high levels. The high PARP-1 expression at ed18 corresponds with the onset of terminal differentiation of the gas exchange epithelium (36,37). This finding is consistent with results from the adipocyte (12) and chick limb differentiation models (11), in which predifferentiation peaks in PARP-1 expression and activity were demonstrated.…”

Apoptosis in Lung Development and Neonatal Lung Injury

“…Looking like a primitive gland, the developing lung enters the pseudoglandular stage. During this period, most of the branching morphogenesis takes place (7). In the subsequent canalicular stage the bronchial tree is established, vascularization increases rapidly, respiratory bronchioli appear, interstitial tissue decreases, and the epithelial barrier thins out as the capillaries begin to lie in close apposition to the epithelium, forming the eventual air-blood barrier (7).…”

“…During this period, most of the branching morphogenesis takes place (7). In the subsequent canalicular stage the bronchial tree is established, vascularization increases rapidly, respiratory bronchioli appear, interstitial tissue decreases, and the epithelial barrier thins out as the capillaries begin to lie in close apposition to the epithelium, forming the eventual air-blood barrier (7). By the end of this stage, airway branching is complete and the distal cuboidal epithelium begins to differentiate into alveolar epithelial type II cells (AEC2) and alveolar epithelial type I cells (AEC1), responsible for surfactant production and gas exchange, respectively (7).…”