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Mild vitamin A deficiency delays fetal lung maturation in the rat
B Chailley-Heu1, N Chelly, M Lelièvre-Pégorier
1INSERM U319, Développement Normal et Pathologique des Fonctions Epithéliales, Université Paris 7-Denis Diderot, Paris, France.
Insights
Vitamin A deficiency in pregnant rats reduced fetal lung surfactant phospholipids and proteins, delaying lung maturation. This may increase the risk of respiratory distress syndrome (RDS) in newborns, especially premature infants.
Area of Science:
- Neonatal physiology
- Nutritional science
- Pulmonary medicine
Background:
- Fetal lung surfactant is crucial for extrauterine respiration.
- Surfactant deficiency, often linked to prematurity, causes neonatal respiratory distress syndrome (RDS).
- Vitamin A's role in surfactant protein synthesis and the impact of its deficiency on fetal lung development remain unclear.
Purpose of the Study:
- To investigate the effects of partial vitamin A deficiency on fetal lung surfactant phospholipid and protein synthesis in rats.
- To assess the impact of vitamin A restriction on the expression of surfactant protein-B (SP-B) and other surfactant components.
- To determine if vitamin A deficiency contributes to lung maturational delay in fetuses.
Main Methods:
- Induced partial vitamin A deficiency in pregnant rats, achieving a 30-60% reduction in blood retinol.
- Analyzed fetal lung surfactant phospholipids, including disaturated phosphatidylcholine (DSPC).
- Quantified messenger RNA (mRNA) levels for surfactant proteins (SP-A, SP-B, SP-C) and fatty acid synthase. Assessed SP-A and SP-B protein levels using Western blotting.
Main Results:
- Vitamin A-deficient fetuses showed reduced lung surfactant phospholipids (21%) and DSPC (27%), correlating with plasma retinol levels.
- Expression of genes for surfactant proteins SP-A, SP-B, and SP-C, as well as fatty acid synthase, was significantly decreased in deficient fetuses.
- SP-A and SP-B protein levels were diminished in vitamin A-deficient fetuses, indicating impaired synthesis.
- The proportion of type II cells remained unchanged, suggesting a specific impact on surfactant production rather than cell numbers.
Conclusions:
- Partial vitamin A deficiency causes a delay in fetal lung maturation in rats.
- Reduced surfactant phospholipids and proteins due to vitamin A deficiency may impair neonatal respiratory function.
- Vitamin A deficiency could be a risk factor for RDS and exacerbate complications of prematurity in human infants.
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.