EFFECT OF TRIAMCINOLONE ACETONIDE ON THE DEVELOPMENT OF THE PULMONARYAIRWAYS IN THE FETAL-RAT

Triamcinolone acetonide (TAC) has a potent teratogenic effect on vario us mammalian fetal tissues as well as a steroid effect on the lung. Le ss well documented is the fact that it produces profound oligohydramni os. We wished to determine what effect TAC would have on branching mor phogenesis and other aspects of lung development, using an in vivo mod el described previously. Thirty rats were randomized to receive 0.6 mg /kg of TAC or saline on days 12, 13, and 14 of gestation. At gestation al days 15, 17, 18,and 21, the left lungs of 365 fetuses were studied by dissecting microscopy, histology, and morphometry. TAC produced pro found pulmonary hypoplasia (dry lung weight/body weight 0.025, compare d with 0.06 in controls) on day 21. TAC decreased maternal weight gain , fetal weight, placental weight, amniotic fluid, and pole to pole len gth (PTP), while it increased the peripheral airway count (PAC). The n umber of central and intermediate airway branches was reduced, and the y were dilated. Growth of peripheral airways was enhanced. In treated fetuses epithelial cells lining these airspaces were histologically mo re mature and the mesenchyme thinner than in controls. These findings were confirmed by the morphometric measurements. We conclude that when TAC is administered in the early phase of fetal rat lung development, the lungs become hypoplastic, with hypoplasia of the intermediate air ways, an increase in the number of peripheral airways, and increased d ifferentiation. We speculate that these effects are primarily due to t he steroid action of TAC and that the mechanisms of monopodial branchi ng are different from those of dichotomous branching. (C) 1997 Wiley-L iss, Inc.