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

Academic Article

Abstract

  • 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, Alveolar Epithelial Cells, Animals, Animals, Newborn, Female, Mice, Inbred C57BL, Pregnancy, Respiratory Function Tests, Trachea, Vitamin D, Vitamin D Deficiency
  • Digital Object Identifier (doi)

    Author List

  • Saadoon A; Ambalavanan N; Zinn K; Ashraf AP; MacEwen M; Nicola T; Fanucchi MV; Harris WT
  • Start Page

  • 383
  • End Page

  • 392
  • Volume

  • 56
  • Issue

  • 3