Acceleration of Canalicular Development in Lungs of Fetal Mice Exposed Transplacentally to Dexamethasone

Morphometric techniques were used to compare the volume density of air space (Vva) and the degree of maturation of pulmonary epithelium in normal fetal mouse lung and in lungs of fetuses exposed transplacentally to dexamethasone. Pregnant Bagg-Webster Swiss mice of 16 days' gestation were given injections of either saline or dexamethasone in doses ranging from 0.40 to 12.0 microng. per gm. of body weight, and killed at intervals thereafter. Fetuses were removed and weighed and their lungs prepared for morphometry using osmium-fixed, Epon-embedded tissue. In control lungs, Vva increased 10-fold between days 17 and 19, an increase from 1.5 to 15%. A 25-fold increase occurred during the same period in test fetal lungs exposed to 0.40 microng. per gm. or more of dexamethasone. When the degree of air space development was compared 24 hours after exposure, within a single weight group and, according to dose, a linear increase in air space was found; 0.1-microng. per gm. increment in dexamethasone produced a 0.66% increment in Vva. Body weight was an important determinant, in that fetuses in the lower weight range had much less response. The latter showed an increment of approximately 0.25% in Vva for each 0.1-microng. per gm. increment of dexamethasone. It can be emphasized from the present experiments that a maximal development of Vva could be achieved by amounts of dexamethasone too low to depress fetal or lung weight. The proportion of pulmonary epithelial cells containing osmiophilic granules increased in control lungs from 18% on day 17 to 42% on day 18. Test fetuses (17 days old) examined 24 hours after receiving either 0.40 or 0.80 microng. per mg. of dexamethasone showed no significant increase in this proportion; however, a significant increase in the proportion of cells containing osmiophilic granules was found in fetal lungs exposed to 2.0 microng. per mg. Whereas a significant increase in Vva was found within 14 hours of exposure, no increase in the proportion of cells containig osmiophilic granules was detectable at this time. It was concluded that air space development is a sensitive method for evaluating the effect of dexamethasone as it gives a clear dose-response curve in fetuses exposed to it 24 hours prior to sacrifice. Accelerated maturation of the presumptive type II cell could only be demonstrated within 24 hours by using higher doses than those required to initiate air space development. These observations suggest that the steps invovled in canal formation, which are assumed to reflect alterations in mesenchyme, may have a different sensitivity to dexamethasone than do those initiating the maturation of alveolar epithelial cells.