Abnormal Fetal Lung of Hoxa1−/− Piglets Is Rescued by Maternal Feeding with All-Trans Retinoic Acid

Abstract

Neonatal Hoxa1−/− piglets were characterized by dyspnea owing to the Hoxa1 mutation, and maternal administration with ATRA alleviated the dyspnea of neonatal Hoxa1−/− piglets. The purpose of this experiment was to explore how maternal ATRA administration rescued the abnormal fetal lungs of Hoxa1−/− piglets. Samples of the lungs were collected from neonatal Hoxa1−/− and non-Hoxa1−/− piglets delivered by sows in the control group, and from neonatal Hoxa1−/− piglets born by sows administered with ATRA at 4 mg/kg body weight on dpc 12, 13, or 14, respectively. These were used for the analysis of ELISA, histological morphology, immunofluorescence staining, immunohistochemistry staining, and quantitative real-time PCR. The results indicate that the Hoxa1 mutation had adverse impacts on the development of the alveoli and pulmonary microvessels of Hoxa1−/− piglets. Maternal administration with ATRA at 4 mg/kg body weight on dpc 14 rescued the abnormal lung development of Hoxa1−/− piglets by increasing the IFN-γ concentration (p < 0.05), airspace area (p < 0.01) and pulmonary microvessel density (p < 0.01); increasing the expression of VEGFD (p < 0.01), PDGFD (p < 0.01), KDR (p < 0.01), ID1 (p < 0.01), and NEDD4 (p < 0.01); and decreasing the septal wall thickness (p < 0.01) and the expression of SFTPC (p < 0.01) and FOXO3 (p < 0.01). Maternal administration with ATRA plays a vital role in rescuing the abnormal development of lung of Hoxa1−/− fetal piglets.