Effect of Prenatal Glucocorticoid on Fetal Lung Ultrastructural Maturation in hyt/hyt Mice with Primary Hypothyroidism

Abstract

Glucocorticoids (GC) and thyroid hormones (TH) accelerate fetal lung maturation. Though GC are used clinically, the mechanisms of GC-induced fetal lung maturity remain unclear. Prenatal GC increase fetal TH activity in humans and in animals. Thus, it is possible that increased fetal TH activity after prenatal GC plays a role in accelerating fetal lung maturation. However, this hypothesis has remained untested due to the lack of a suitable animal model. In the hyt/hyt mouse primary hypothyroidism occurs due to a point mutation in the beta subunit of the thyroid-stimulating hormone receptor of the thyroid gland, and it is transmitted in an autosomal recessive manner. We studied the effect of maternal betamethasone on fetal lung ultrastructure in hyt/hyt (hypothyroid) and Balb-c (euthyroid) mice. Hypothyroid mice were made euthyroid by T₃ supplementation and mated to carry hypothyroid pups. Vehicle (n = 6) or betamethasone (n = 6) was injected intraperitoneally twice daily into the doe on days 16 and 17 of gestation. Fetal lungs on 18 days of gestation were subjected to ultrastructural morphometric analysis. The number of lamellar bodies per type II cell increased after betamethasone in Balb-c (2.10 ± 0.31 vs. 3.43 ± 0.37) and hyt/hyt (0.77 ±0.28 vs. 3.85 ± 0.26) mice. The alveolar-to-parenchymal ratio was less in the vehicle-treated hyt/hyt (0.082 ± 0.024) as compared with the vehicle-treated Balb-c (0.30 ± 0.05) mice, while prenatal betamethasone increased the alveolar-to-parenchymal ratio in the hyt/hyt (0.227 ± 0.034) but not in the Balb-c (0.26 ± 0.04) mice. The glycogen-to-nucleus ratio was higher in betamethasone-treated hyt/hyt mice (1.46 ± 0.20) when compared to vehicle-treated hyt/hyt (0.89 ± 0.14) or Balb-c (1.01 ± 0.17) or betamethasone-treated Balb-c (0.81 ± 0.13) mice. Though tubular myelin was readily apparent in the airspace lumen of betamethasone-treated Balb-c mice, it was absent in betamethasone-treated hyt/hyt fetal lungs. We conclude that fetal thyroid plays an important role in accelerating some aspects of fetal lung ultrastructural maturation from GC stimulation.