Mild vitamin A deficiency delays fetal lung maturation in the rat

During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, pr ecipitates respiratory distress syndrome (RDS) of the neonate. Although vit amin A (retinol) and retinoic acid have been shown to enhance the synthesis of phospholipid surfactant components, their effect on surfactant-specific proteins is unclear. No attempt has been made to evaluate the consequences of vitamin A restriction on surfactant phospholipid storage or on the expr ession of the life-essential surfactant protein-B (SP-B). We induced in rat s a partial vitamin A deficiency leading to a 30-60% reduction in blood ret inol, a status compatible with maintenance of gestation and absence of gros s abnormalities in offspring. At term, lang surfactant phospholipids were r educed by 21%, and the major surfactant phospholipid, disaturated phosphati dylcholine (DSPC), was reduced by 27% in vitamin A-deficient (VAD) fetuses. The decrease in surfactant phospholipids and DSPC correlated linearly with plasma retinol, and reached about 50% in fetuses with the lowest retinol c oncentrations; it was accompanied by reduced expression of the gene for fat ty acid synthase, a key enzyme in the synthetic pathway for surfactant-phos pholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RN As were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consi stently, amounts of SP-A and SP-B proteins were diminished as assessed by W estern blotting. The proportion of type Ii cells determined after SP-B labe ling was unchanged in VAD as compared with control lungs. Vitamin A deficie ncy is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk fo r RDS and an aggravating factor for prematurity.