Differential effects of vitamin A on fetal lung growth and diaphragmatic formation in nitrofen-induced rat model

Congenital diaphragmatic hernia (CDH) is associated with high neonatal mortality and morbidity due to pulmonary hypoplasia and pulmonary hypertension. Antenatal interventions have been developed in an attempt to reduce the unacceptable mortality rate of CDH. The pathogenesis of pulmonary hypoplasia is not fully understood. It is not clear whether the increase of lung growth would be necessary for diaphragmatic closure. Vitamin A is important for various aspects of lung development. Therefore, the aim of this study was to examine whether antenatal treatment with vitamin A can increase lung growth and reduce the incidence of CDH in a nitrofen-treated rat model. The animals were randomly assigned to four groups: control, vitamin A, nitrofen, and nitrofen/vitamin A (NIP/Vit A). The incidence of CDH in the NIP/Vit A group (54%) was markedly lower than that in the nitrofen-treated group (85%). Although lung weight was decreased in the nitrofen-treated and NIP/vitamin A groups, the fetal lung weight-to-body weight ratio was slightly increased in the NIP/vitamin A group, compared to the nitrofen-treated group. The mRNA levels of lung surfactant proteins were decreased in the NIP/vitamin A group. We conclude that antenatal treatment with vitamin A reduced the incidence of CDH without lung maturation in the nitrofen-induced rat model.