DELAYED ULTRASTRUCTURAL LUNG MATURATION IN THE FETAL AND NEWBORN HYPOTHYROID (HYT HYT) MOUSE/

Thyroid hormones influence fetal and neonatal lung growth and maturati on. However, the effect of naturally occurring, genetically determined hypo- or hyperthyroidism on fetal or neonatal lung maturation has not been examined. In the hyt/hyt mouse, primary hypothyroidism, which is characterized by a high serum TSH concentration, is transmitted as an autosomal recessive trait. It occurs due to a mutational defect in th e beta-subunit of the TSH receptor. We studied the lung ultrastructure of the fetal [18-d-gestation (term = similar to 19.5 d)] and neonatal (<1-d-old) hyt/ hyt mouse. In addition, disaturated phosphatidylcholi ne and total phospholipid contents of newborn hyt/hyt mouse lungs were determined. Male and female hyt/hyt mice with a high serum TSH concen tration were made euthyroid by adding 3,5,3'-triiodothyronine to drink ing water and then mated. Balb-c mice served as euthyroid controls. Fe tal and neonatal hyt/hyt mice had a higher serum TSH concentration tha n the Balb-c controls. Fetal hyt/hyt mouse lungs showed a large amount of intracellular glycogen and fewer lamellar bodies in epithelial typ e II cells compared with Balb-c fetal mouse lungs. The neonatal hyt/hy t mouse also showed signs of lung immaturity such as persistent epithe lial cell glycogen, few lamellar bodies, reduced disaturated phosphati dylcholine content, and absent tubular myelin. We conclude that fetal and neonatal lung maturation is delayed in the hyt/hyt mouse with prim ary hypothyroidism.