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

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Abstract
Retinoic acid exposure has been shown to promote surfactant produc- tion in foetal rats and to promote alveolization in neonatal rats. It was hypothesized that antenatal retinoic acid treatment would promote alveolization and accelerate functional maturation in the lungs of late gestation preterm sheep. Foetuses received a single i.m. injection of all-trans retinoic acid (RA, 20 mg.kg-1 )o r vehicle control at 115 days gestation (term=150 days) and were delivered at 125 days gestation. To examine the longer term effects of RA on alveolization a second group of animals received RA or vehicle at 121 days gestation and were delivered at 146 days gestation. Liver retinol levels at time of delivery were 2-3-fold higher in both preterm and near-term RA treated animals, indicating a significant impact of RA treatment on retinol metabolism. Dynamic compliance, gas exchange, lung gas volume and satu- rated phosphatidylcholine pool size at 125 days were unaffected by antenatal RA treatment. Alveolar volume, wall thickness and number at 125 or 146 days were also unaffected by RA treatment. Retinoic acid, as administered in this study, does not appear to accelerate structural or functional maturation of the foetal sheep lung. Response to retinoic acid may be species dependent, highlighting a need for caution when interpreting results from animal based studies. Eur Respir J 2000; 16: 101-107.

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