Vitamin D treatment improves survival and infant lung structure after intra-amniotic endotoxin exposure in rats: potential role for the prevention of bronchopulmonary dysplasia

Vitamin D (vit D) has anti-inflammatory properties and modulates lung growth, but whether vit D can prevent lung injury after exposure to antenatal inflammation is unknown. We hypothesized that early and sustained vit D treatment could improve survival and preserve lung growth in an experimental model of bronchopulmonary dysplasia induced by antenatal exposure to endotoxin (ETX). Fetal rats (E20) were exposed to ETX (10 μg), ETX + Vit D (1 ng/ml), or saline (control) via intra-amniotic (IA) injections and delivered 2 days later. Newborn pups exposed to IA ETX received daily intraperitoneal injections of vit D (1 ng/g) or saline for 14 days. Vit D treatment improved oxygen saturations (78 vs. 87%; P < 0.001) and postnatal survival (84% vs. 57%; P < 0.001) after exposure to IA ETX compared with IA ETX alone. Postnatal vit D treatment improved alveolar and vascular growth at 14 days by 45% and 25%, respectively (P < 0.05). Vit D increased fetal sheep pulmonary artery endothelial cell (PAEC) growth and tube formation by 64% and 44%, respectively (P < 0.001), and prevented ETX-induced reductions of PAEC growth and tube formation. Vit D directly increased fetal alveolar type II cell (ATIIC) growth by 26% (P < 0.001) and enhanced ATIIC growth in the presence of ETX-induced growth suppression by 73% (P < 0.001). We conclude that antenatal vit D therapy improved oxygenation and survival in newborn rat pups and enhanced late lung structure after exposure to IA ETX in vivo, which may partly be due to direct effects on vascular and alveolar growth.