Antenatal retinoic acid does not alter alveolization or postnatal lung function in preterm sheep

Area of Science:

• Developmental biology
• Pulmonology
• Pharmacology

Background:

• Retinoic acid (RA) promotes lung development in rodents.
• Alveolization and lung maturation are critical for preterm infants.
• The efficacy of antenatal RA in ovine lung development is unknown.

Purpose of the Study:

• To investigate if antenatal all-trans retinoic acid (RA) administration accelerates lung alveolization and functional maturation in late gestation preterm sheep.
• To assess the impact of RA on lung structure and gas exchange in ovine fetuses.

Main Methods:

• Ovine fetuses received intramuscular injections of all-trans retinoic acid (RA) or vehicle at 115 or 121 days of gestation.
• Animals were delivered prematurely (125 days) or near term (146 days) for analysis.
• Lung structure, gas exchange, and retinol metabolism were assessed.

Main Results:

• Antenatal RA treatment significantly increased liver retinol levels in treated animals.
• No significant differences were observed in dynamic compliance, gas exchange, lung gas volume, or saturated phosphatidylcholine pool size.
• Alveolar development, including volume, wall thickness, and number, remained unaffected by RA treatment at either gestational age.

Conclusions:

• Antenatal retinoic acid administration, as studied, does not accelerate structural or functional maturation of the fetal sheep lung.
• The response to retinoic acid in lung development may be species-dependent.
• Caution is advised when extrapolating findings from rodent studies to other species, including humans.