Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque

To test the effect of dose and time on fetal lung maturation by exogenous glucocorticosteroids, triamcinolone acetonide was given to time-mated pregnant rhesus macaques (Macaca mulatta). Triamcinolone acetonide (10 mg/kg or 1 mg/kg) was administered intramuscularly during the midpseudoglandular (63 to 65 days' gestational age) or midcanalicular phase (110 to 112 days' gestational age) of lung development. Fetectomies were performed at 90, 120, or 150 days' gestational age. Nontreated control fetuses and postnatal animals from 59 days' gestational age to 31 days' postnatal age were collected for study of normal developmental lung morphology in the rhesus monkey. Lungs from fetuses of 90 days' gestational age and older were fixed by tracheal infusion, and lungs from fetuses less than 90 days' gestational age were fixed by immersion and embedded for high-resolution light microscopy. Body weight, crown-rump length, and fixed lung volume were determined for all fetuses. Morphometric evaluation of the volume percent of parenchyma, the volume percent of air space and the mean linear intercept as an estimate of air space size was also done. Lungs from fetuses treated during the canalicular phase had thinner, longer, less cellular septa, larger air spaces, and increased numbers of alveolar divisions in terminal air spaces as compared to those of controls. Lungs of fetuses treated during the pseudoglandular phase also had some septa which were thinner, less cellular, and longer than those of controls and had a marked increase in air space size. However, most septa were greatly reduced in height and appeared fewer in number. Alveolar divisions were decreased. The volume percent of air space was larger in all treated groups. Fixed lung volume normalized to body size (body weight and crown-rump length) was greater than that for controls for the high-dose canalicular phase treatment group. The same parameter was lower than that of controls for the high-dose, pseudoglandular phase treatment group of 150 days' gestational age. Body weight and crown-rump length for all pseudoglandular phase triamcinolone acetonide-treated fetuses also tended to be lower than those of controls. We concluded that: (1) there is both a time-dependent and a dose-dependent effect on triamcinolone acetonide on fetal lung maturation in rhesus macaques, (2) triamcinolone acetonide accelerates maturation of the interstitial and epithelial component of the developing fetal rhesus lung independent of age, (3) triamcinolone acetonide accelerates alveolarization only at later treatment ages, and (4) triamcinolone acetonide induces retardation of growth of some of the lung septa and body growth only