title: Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice.
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.
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: Ammar
authors.identifier: 0000-0003-3160-6964
authors.initials: A
authors.lastname: Saadoon
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
authors.affiliation: 2 Radiology, and.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zinn
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: Ambika P
authors.initials: AP
authors.lastname: Ashraf
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: Mark
authors.initials: M
authors.lastname: MacEwen
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: Teodora
authors.initials: T
authors.lastname: Nicola
authors.affiliation: 3 Environmental Health Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
authors.forename: Michelle V
authors.initials: MV
authors.lastname: Fanucchi
authors.affiliation: 1 Departments of Pediatrics.
authors.forename: William T
authors.initials: WT
authors.lastname: Harris
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D012129:Respiratory Function Tests; D014132:Trachea / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D014807:Vitamin D / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000473:pathology* / Q000503:physiopathology
chemical_list: D014807:Vitamin D
keywords: lung development; murine model; pulmonary function; tracheal ultrasound; vitamin D deficiency