Postnatal mammalian Lung development: The normal Events In a Marsupial, the Quokka Wallaby (Setonix Brachyurusi and the effects of Glucocorticoid treatment in a eutherian, the Rat (Rattus Norvegicusi).
The lungs of a marsupial, the quokka wallaby (Setonix brachyurus) were examined morphologically and morphometric ally at diverse age points from 3 days post partum to adulthood and the qualitative and quantitative changes during postnatal development determined. The objective of this approach was to establish the developmental events taking place at various stages of the postnatal lung development in the quokka and also to study the lung morphology in the adult quokka. The four stages of postnatal lung development in the quokka namely, the canalicular (0-4 days), the saccular (5-125 days), the alveolar (125-180 days) and the microvascular maturation (150-400 days) were investigated. The ultimate goal was to establish a potential animal model that would allow flexibility in drug testing in terms of the developmental stages available postnatally and their respective timescales. Macroscopically the lung had a single left lobe, a right lobe and an accessory lobe. A variable number of fissures divided the lung lobes into pseudo-lobes and some indentations were observable on the parietal edges of the lobes. Microscopically, the primitive tubules of the canalicular stage were converted to large saccules by day 5 with secondary septa arising by day 15. There was subsequent reduction of size of air spaces, which lasted through the saccular and alveolar stages. There was increase in air space size during the stage of microvascular maturation coupled with thinning of interalveolar septa and development of pores of Kohn. Early in the canalicular stage, the.tubules were lined with a low cuboidal epithelium interrupted by a few isolated areas of the first thin portions of gas exchange barrier. The septal interstitium was predominantly mesenchymal with no definitively identifiable cell morphophenotypes. Towards the onset of saccular stage of development, gas exchange barriers increased in number and much of the cuboidal epithelium changed to the squamous type. Quantitative analysis at light microscopy involved coarse lung parameters, which included the volumes of the parenchyma, septal tissue, the non-parenchyma, and the components of the latter, which included blood vessels, airways and connective tissue. Between mid-canalicular stage and the onset of saccular stage, the lung volume increased two-fold when major components of both the parenchyma and nonparenchyma were laid down. The dramatic increase in volume was, however, mainly due to air space expansion as tubules converted to saccules, coupled with septal tissue thinning. Except for the vascular component of the non-parenchyma, rate of increase of the other parameters progressed in a decreasing order, being highest in the canalicular and saccular stages and lowest in the alveolar stage, increasing again in the microvascular maturation stage. It would appear that during the alveolar stage, the main events involved growth and remodelling of the alveolar septa with air space subdivision but with no marked tissue proliferation or air space expansion. Air space expansion followed in the later part of alveolar stage and in the microvascular maturation stage. The final adult lung volume was achieved by the process of equilibrated growth. At ultrastructural ~vel the parameters estimated included the volumes of septal tissue ". cotnponents and those of the air ~p'aces together with their respective surface areas. Further tissue barrier. thicknesses and their diffusion capacities were computed. Most parameters quantified showed a positive correlation with body mass in all the developmental stages, except the volume of type II pneumocytes during the alveolar stage when no significant correlation was observed. The volumes of the interstitium and type II cells increased early in the saccular stage, the rate declining later in the alveolar stage. Conversely, the volume of type I pneumocytes increased markedly in both saccular and alveolar stages. Both capillary and endothelial volumes showed highest rates of increase during the alveolar stage, a fact reflected also in the increase in capillary surface area. Increase in alveolar surface area reached a peak during the alveolar stage. The pulmonary diffusion capacity increased gradually, the rate being highest in the saccular stage and the adult values attained were comparable to those of eutherians. Although the quokka wallaby is born with the lung at a stage earlier than any other reported mammal, the subsequent developmental stages characteristic of all mammals were meticulously recapitulated. From the current findings, the quokka is potentially an excellent animal model for testing paediatric drugs aimed at management of lung related diseases. On an already well-studied animal model, the laboratory rat (Rattus norvergicus) high doses of dexamethasone phosphate were administered in the first 4 days of life to test the effects of this drug on the morpho functional characteristics of the lung in the immediate and prolonged post treatment period. At the fourth postnatal day, the treated animals had rather enlarged air spaces, the interalveolar septa were thinner and more mature with a single capillary system and secondary septa were few compared to the lungs of the control rats. By day 10 post partum, the situation in the dexamethasone treated rats was reversed the septa in the lungs of the treated rats were much thicker and had acquired a double capillary system, showing a new potency for secondary septa formation. Secondary septa were obviously more numerous in the experimental animals and had fewer mature septa at postnatal day 10. The morphology of the lung parenchyma at 21 days was not much different between the control and experimental animals, save for the rugged appearance of the septa in the latter group. Dexamethasone treatment did not appear to confer any morpho-functional advantages to the lung. Body weight-normalized lung volume was boosted by day 21 at which time body weight was depressed. Despite an improvement in the parenchymal proportion and capillary surface area by day 4 post partum, there was no significant increase in the pulmonary diffusing capacity in the experimental animals. At day 60 postpartum, there were no observable qualitative or quantitative differences. From these findings, it is clear that dexamethasone treatment in postnatal life leads to a precocious maturation of the septa and probably to an improved surfactant production and hence its observed positive aspects in improving breathing in premature neonates. The treatment regime of high-dose, short-term administration adopted here appears ideal since all the morphological alterations undergo a reparative process by 36 days post partum. This is indeed the protocol used by ciin'icians and the current study puts to rest the fears that there might be long-term deleterious pulmonary effects after early treatment with glucocorticoids. The effects of glucocorticoids prior to the saccular stage remain unclear but as seen in the current study, .the quokka wallaby offers an opportune animal model to introduce such drugs at the canalicular stage of development.
CitationDoctor of Philosophy (Ph.D.) degree in Veterinary Anatomy, University of Nairobi, 1990
University of NairobiDepartment of Veterinary Anatomy