Feeding All-Trans Retinoic Acid to Pregnant Sows Regulates the Development of the Pulmonary Nervous Systems of Neonatal Pigs

Newborn piglets in intensive pig farms are often prone to pulmonary diseases due to underdeveloped fetal lung neural systems, and ATRA is often regarded as an important morphogen that displays pleiotropic functions during embryonic development. However, information about the effect of maternal administration with ATRA on the peripheral neural system of fetal lungs is still scare. Fifteen pregnant sows were assigned to the ATRA0 (0 mg/kg diet), ATRA4, ATRA8, ATRA16 and ATRA32 treatment groups and offered their own feed from d12 to d95 after artificial insemination; then two neonatal pigs with birth weights similar to the average birth weight were taken out from each litter for the collection of lung samples, and samples were subjected to immunofluorescence staining, RNA-seq and RT-qPCR assays. Results indicated that compared to newborn piglets from the ATRA0 treatment group, newborn piglets from the ATRA4 treatment group had higher percentages of GFAP-positive astrocyte cells (p < 0.05) and GFAP-TUBB3 colocalization (p < 0.05) in the lungs. KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that differential expressed genes are mainly enriched in the pathways of neuroactive ligand–receptor interaction, GABAergic synapses and cell adhesion molecules. Addition of ATRA at 4 mg/kg to the diet of pregnant sows can enhance the healthy development of the pulmonary nervous systems of fetal pigs.