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Groups of fetal monkeys were studied at 50, 75, 100, 125 and 150 days gestational age, and postnatal monkeys were studied at 175 days gestational age and in adult life (full term gestation is 168 plus or minus 4 days). The ratios between the various tissues of which lung is composed were determined by light and electronmicroscopy. Characteristic changes in ratios were noted at each developmental age. Primitive bronchioles increased from 50 to 75 days, decreased as permanent bronchioles, alveolar ducts and alveoli developed, and were absent after 150 days. Mesenchymal tissue decreased progressively from 50 to 150 days. Alveoli were present at 100 days gestational age; alveolar lumens accounted for approximately 1/2 the volume of peripheral lung by 150 days, and 2/3 the volume of lung in adult animals. By 150 days alveolar epithelial cells could be identified as Type I (membranous) or Type II (granular) on the basis of the characteristic cytoplasmic lamellar inclusion bodies of the latter. The ratios of the Type II/Type I cells were .21-.23 at 150 and 175 days, and fell to approximately half that value in adult lungs.

Previous investigations of the effect of glucocorticoids on fetal lung development have suggested that changes in lung structural properties may be of greater functional significance than changes in lung surfactant. In this study we examined the mechanism of the glucocorticoid-induced change in lung structure and compared it with the changes that occur during normal development. Rhesus monkeys (Macaca Mulatta) were treated with betamethasone prior to 133 days gestational age and then delivered by cesarian section either at 133 days or near term at 160 days. Our results show that normal fetal lung development over the last month of gestation occurs with a 45% increase in lung dry weight and a 56% increase in the maximal air volume per gram lung (Vmax/g). The immediate effect of the steroid was to cause a similar percentage increase in Vmax/g but no increase in lung weight. In fact, there were significant decreases in lung weight at both 133 and 160 days in the treated animals. In addition, we found no significant changes in the mean alveolar size either with normal development or with the steroid treatment. We thus conclude that in the rhesus monkey, the lung maturation process involves both an increase in lung mass and an increase in the number of alveoli per gram of that mass. The betamethasone treatment results in accelerated recruitment of alveoli coupled with impaired growth of lung tissue.

In the monkey lung (Macacus nemestrina) canalization of all bronchopulmonary segments begins simultaneously at the peripheral future-alveolar-duct portions of each segment and then continues progressively centralwards. Its simulataneous appearance in all segments of a human lung of the 17th postovulatory week (19th postmenstrual week) has now been confirmed (cf. Boyden, '74). The mode of canalization, as seen under the light microscope, is here demonstrated.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Immunoreactivity of regulatory peptides has been demonstrated in the fetal lung of Macaca mulatta by the peroxidase anti-peroxidase method. Serotonin-immunoreactive neuroepithelial bodies are distributed in the airways from the bronchi to the alveolar ducts. Many neuroepithelial bodies also show bombesin-like immunoreactivity; a very few are immunoreactive to somatostatin antiserum. Four populations of neuroepithelial bodies were identified which contain immunoreactivity for 1) serotonin alone, 2) serotonin and bombesin, 3) serotonin and somatostatin, and 4) serotonin, bombesin, and somatostatin. Since bombesin and somatostatin have been demonstrated to have opposite effects on the release of other peptide hormones, it seems likely that the presence of these same peptides in neuroepithelial bodies may have a similar regulatory role in the lung.