Moderate maternal nutrient restriction alters type II alveolar epithelial cell density in the non‐human primate fetal lung

Abstract Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero. However, the consequences of reduced fetal substrate supply are dependent on the timing of gestation, severity and duration. We hypothesise that maternal nutrient restriction (MNR) from early pregnancy negatively impacts fetal lung maturation. Female baboons of similar age and weight were randomly assigned to either a control diet (n = 3F, 5M offspring) or MNR (n = 4F, 4M offspring). On a weight‐adjusted basis, MNR animals were fed 70% of the feed consumed by controls. Fetal lung tissue was collected at 0.9 gestation (term = 184 days). qRT‐PCR and immunohistochemistry were utilised to measure expression of key molecules involved in surfactant maturation, reabsorption of lung liquid, vascularisation and immune cells. MNR decreased type II alveolar epithelial cell density and the mRNA expression of PCYT1A, the gene for choline‐phosphate cytidylyltransferase A, the enzyme required for de novo surfactant phospholipid synthesis. However, MNR had no effect on the expression of surfactant proteins in the fetal lung. There was a reduced number of α‐smooth muscle actin‐stained vessels and presence of CD45+ immune cells within the lung of fetuses exposed to MNR. These data indicate that MNR from early pregnancy increases risk of neonatal respiratory complications at birth by impairing the capacity for surfactant maturation, reducing vascularisation within the fetal lung and impairing innate lung immunity.