Mechanism of Oligohydramnios-induced Pulmonary Hypoplasia

Pulmonary hypoplasia is common in the perinatal period and is a significant cause of death in newborn infants, and oligohydramnios is one of the most commonly associated abnormalities. Neonates exposed to oligohydramnios caused by premature rupture of membranes have an increased risk of acute respiratory morbidity. The exact mechanism by which oligohydramnios alters the respiratory system remains unknown. We herein report the effects of experimental oligohydramnios on lung growth and the expressions of growth factors and extracellular matrix in fetal rats on days 19 and 21 of gestation by producing oligohydramnios from days 16 to 21 of gestation in Sprague-Dawley dams. Rats exposed to oligohydramnios exhibited lung hypoplasia and significantly decreased expressions of extracellular matrix, transforming growth factor-β1 and platelet-derived growth factor on days 19 and 21 of gestation. Concomitant maternal retinoic acid treatment at a dose of 10 mg/kg increased platelet-derived growth factor expression but did not enhance fetal lung development. These results suggest that there is a stage-specific requirement for retinoic acid during lung development, and retinoic acid treatment should be applied with caution.