title: Mild vitamin A deficiency delays fetal lung maturation in the rat.
abstract: During late pregnancy, the fetal lung stores surfactant in preparation for extrauterine life. Surfactant deficiency, most often due to prematurity, precipitates respiratory distress syndrome (RDS) of the neonate. Although vitamin 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 expression of the life-essential surfactant protein-B (SP-B). We induced in rats a partial vitamin A deficiency leading to a 30-60% reduction in blood retinol, a status compatible with maintenance of gestation and absence of gross abnormalities in offspring. At term, lung surfactant phospholipids were reduced by 21%, and the major surfactant phospholipid, disaturated phosphatidylcholine (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 concentrations; it was accompanied by reduced expression of the gene for fatty acid synthase, a key enzyme in the synthetic pathway for surfactant-phospholipid lipid precursors. The amounts of SP-A, SP-B, and SP-C messenger RNAs were decreased by 46%, 32%, and 28%, respectively, in VAD fetuses. Consistently, amounts of SP-A and SP-B proteins were diminished as assessed by Western blotting. The proportion of type II cells determined after SP-B labeling was unchanged in VAD as compared with control lungs. Vitamin A deficiency is therefore a cause of lung maturational delay. In view of its rather large incidence in human populations, it may represent an increased risk for RDS and an aggravating factor for prematurity.
authors.affiliation: INSERM U319, Développement Normal et Pathologique des Fonctions Epithéliales, Université Paris 7-Denis Diderot, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Chailley-Heu
authors.forename: N
authors.initials: N
authors.lastname: Chelly
authors.forename: M
authors.initials: M
authors.lastname: Lelièvre-Pégorier
authors.forename: A M
authors.initials: AM
authors.lastname: Barlier-Mur
authors.forename: C
authors.initials: C
authors.lastname: Merlet-Bénichou
authors.forename: J R
authors.initials: JR
authors.lastname: Bourbon
mesh_terms: D000818:Animals; D019916:Choline-Phosphate Cytidylyltransferase / Q000032:analysis; D004224:Diterpenes; D005260:Female; D008168:Lung / Q000196:embryology* / Q000201:enzymology; D010743:Phospholipids / Q000032:analysis; D011247:Pregnancy; D011248:Pregnancy Complications; D011270:Pregnancy, Animal; D011663:Pulmonary Surfactants / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood; D014802:Vitamin A Deficiency / Q000196:embryology*
chemical_list: D004224:Diterpenes; D010743:Phospholipids; D011663:Pulmonary Surfactants; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D019916:Choline-Phosphate Cytidylyltransferase