Effects of Maternal Retinoic Acid Administration on Lung Angiogenesis in Oligohydramnios-Exposed Fetal Rats

Abstract

All-trans retinoic acid (ATRA) induces in vitro angiogenesis and vascular endothelial growth factor (VEGF) secretion. Prenatal administration of vitamin A tends to increase the pulmonary and plasma levels of VEGF in the developing mouse. The aims of this study were to examine the effects of maternal retinoic acid treatment on lung VEGF expression and angiogenesis in oligohydramnios-exposed fetal rats. Methods: On day 16 of gestation, pregnant Sprague–Dawley rats were randomly assigned to either the retinoic acid group (intragastric ATRA at 10 mg/kg body weight) or the vehicle group. We punctured each uterine sac to produce oligohydramnios, and fetuses in the opposite uterine horn served as controls. On day 21 of gestation, the fetuses were delivered by cesarean section. Results: Rats exposed to oligohydramnios exhibited lower lung weights and lung/body weight ratios, and ATRA exhibited no effects on the body or lung weights of oligohydramnios-exposed rats. Lung microvessel density decreased in oligohydramnios-exposed rats of maternal vehicle-treated dams. Microvessel density was comparable between the oligohydramnios + retinoic acid group and the control + retinoic acid group. VEGF expression was comparable among control and oligohydramnios-exposed rats of maternal vehicle- or retinoic acid-treated dams. Conclusion: Maternal retinoic acid treatment did not increase lung VEGF expression or enhance lung development in oligohydramnios-exposed fetal rats. These results do not support the use of maternal retinoic acid to prevent oligohydramnios-induced pulmonary hypoplasia in the pseudoglandular stage.

Keywords

• angiogenesis
• oligohydramnios
• retinoic acid
• vascular endothelial growth factor