Maternal Vitamin D deficiency induces transcriptomic changes in newborn rat lungs

Transcriptomic analysis of lungs from newborn rats born to vitamin D adequate and vitamin D deficient mothers Vitamin D deficiency during pregnancy is common and is related to several maternal and fetal morbidities. Past studies suggest that vitamin D plays a role in normal lung development and we have shown that vitamin D regulates lung alveolar and vascular growth and preserves lung structure in experimental bronchopulmonary dysplasia (BPD) through improved pro-angiogeneic signaling. In addition, maternal vitamin D deficiency causes abnormal airway, alveolar, and vascular growth, as well as impaired lung function and airway hyper-reactivity in newborn rats. However, the mechanisms responsible for these physiologic effects are unknown. To gain insight into the role that maternal vitamin D status has on fetal lung development we used an unbiased transcriptomic approach to identify pathways altered in the lungs of offspring from vitamin D deficient dams. We collected lungs from newborn pups born to mothers with adequate or deficient vitamin D nutritional status (n=4 per group). To generate the mothers for our experiments, 4-week-old female rats were obtained from Charles River Laboratories (Wilmington, MA) then maintained in room air at Denver altitude (1,600 m; barometric pressure 630 mmHg; inspired oxygen tension 122 mmHg). Rats were housed in ultraviolet (UV) light-free surroundings using UV A/B blocking films on all light fixtures and they were exposed to a 12 h day- 12 h night cycle. UV A/B levels were verified to be less than 1 W/m2 with Sper Scientific UV A/B light meter. Rats were randomized to be fed ad libitum with semi-purified AIN93G diets containing adequate (1000 IU/kg diet) or no added vitamin D (0 IU/kg diet, VDD); both diets contained 0.5% calcium, and 0.4% phosphorus (Research Diets Inc. New Brunswick NJ). At 8 weeks of age serum 25-OHD levels were determined from blood obtained via the tail vein. If 25-OHD levels were <10 ng/ml, the female mice were mated with vitamin D–replete males. Pups from control and VDD dams were allowed to spontaneously deliver at term.