Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice

Am J Respir Cell Mol Biol. 2017 Mar;56(3):383-392. doi: 10.1165/rcmb.2014-0482OC.


Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by inducing it in pregnant mice and then compared lung development and function in their offspring to littermate controls. Postnatal vitamin D deficiency and sufficiency models from each group were also studied. We developed a novel tracheal ultrasound imaging technique to measure tracheal diameter in vivo. Histological analysis estimated tracheal cartilage total area and thickness. We found that vitamin D-deficient pups had reduced tracheal diameter with decreased tracheal cartilage minimal width. Vitamin D deficiency increased airway resistance and reduced lung compliance, and led to alveolar simplification. Postnatal vitamin D supplementation improved lung function and radial alveolar count, a parameter of alveolar development, but did not correct tracheal narrowing. We conclude that antenatal vitamin D deficiency impairs airway and alveolar development and limits lung function. Reduced tracheal diameter, cartilage irregularity, and alveolar simplification in vitamin D-deficient mice may contribute to increased airways resistance and diminished lung compliance. Vitamin D supplementation after birth improved lung function and, potentially, alveolar simplification, but did not improve defective tracheal structure. This mouse model offers insight into the mechanisms of vitamin D deficiency-associated lung disease and provides an in vivo model for investigating preclinical preventive and therapeutic strategies.

Keywords: lung development; murine model; pulmonary function; tracheal ultrasound; vitamin D deficiency.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / drug effects
  • Alveolar Epithelial Cells / metabolism
  • Alveolar Epithelial Cells / pathology
  • Animals
  • Animals, Newborn
  • Female
  • Mice, Inbred C57BL
  • Pregnancy
  • Respiratory Function Tests
  • Trachea / diagnostic imaging
  • Trachea / drug effects
  • Trachea / pathology*
  • Trachea / physiopathology
  • Vitamin D / pharmacology
  • Vitamin D Deficiency / pathology*
  • Vitamin D Deficiency / physiopathology


  • Vitamin D