ACCELERATION OF CANALICULAR DEVELOPMENT IN LUNGS OF FETAL MICE EXPOSED TRANSPLACENTALLY TO DEXAMETHASONE

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 36  (4) , 395-401
Abstract
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 0.40-12.0 .mu.g/g 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 during days 17-19, an increase from 1.5 to 15%. A 25-fold increase occurred during the same period in test fetal lungs exposed to 0.40 .mu.g/g or more of dexamethasone. When the degree of air space development was compared 24 h after exposure, within a single weight group and, according to dose, a linear increase in air space was found; 0.1 .mu.g/g increment in dexamethasone produced a 0.66% increment in Vva. Body weight was an important determinant, in that fetuses to get lower weight range had much less response. The latter showed an increment of approximately 0.25% in Vva for each 0.1 .mu.g/g increment of dexamethasone. A maximal development of Vva was 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 h after receiving either 0.40 or 0.80 .mu.g/mg of dexamethasone showed no significant increase in this proportion; a significant increase in the proportion of cells containing osmiophilic granules was found in fetal lungs exposed to 2.0 .mu.g/mg. While a significant increase in Vva was found within 14 h of exposure, no increase in the proportion of cells containing osmiophilic granules was detectable at this time. Air space development was a sensitive method for evaluating the effect of dexamethasone as it gave a clear dose-response curve in fetuses exposed to it 24 h prior to sacrifice. Accelerated maturation of the presumptive type II cell was only demonstrated within 24 h by using higher doses than those required to initiate air space development. The steps involved in canal formation, which were assumed to reflect alterations in mesenchyme, may have a different sensitivity to dexamethasone than do those initiating the maturation of alveolar epithelial cells.

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