{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:45:18Z","timestamp":1792028718174,"version":"4.4.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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\u2013deficient 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\u2013deficient 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\u2013associated lung disease and provides an in vivo model for investigating preclinical preventive and therapeutic strategies.<\/jats:p>","DOI":"10.1165\/rcmb.2014-0482oc","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T10:33:42Z","timestamp":1488364422000},"page":"383-392","source":"Crossref","is-referenced-by-count":42,"title":["Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice"],"prefix":"10.1093","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3160-6964","authenticated-orcid":false,"given":"Ammar","family":"Saadoon","sequence":"first","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namasivayam","family":"Ambalavanan","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Zinn","sequence":"additional","affiliation":[{"name":"Radiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambika P.","family":"Ashraf","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"MacEwen","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Nicola","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle V.","family":"Fanucchi","sequence":"additional","affiliation":[{"name":"Environmental Health Sciences, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Harris","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,3,1]]},"reference":[{"key":"2026021122414460600_bib1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/ajcn\/76.1.187","article-title":"Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988\u20131994","volume":"76","author":"Nesby-O\u2019Dell","year":"2002","journal-title":"Am J Clin Nutr"},{"key":"2026021122414460600_bib2","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1093\/jn\/137.2.447","article-title":"High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates","volume":"137","author":"Bodnar","year":"2007","journal-title":"J Nutr"},{"key":"2026021122414460600_bib3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.earlhumdev.2008.10.006","article-title":"Vitamin D intake during pregnancy: association with maternal characteristics and infant birth weight","volume":"85","author":"Scholl","year":"2009","journal-title":"Early Hum Dev"},{"key":"2026021122414460600_bib4","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/ajcn\/85.3.853","article-title":"Maternal vitamin D intake during pregnancy and early childhood wheezing","volume":"85","author":"Devereux","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"2026021122414460600_bib5","doi-asserted-by":"crossref","first-page":"e180","DOI":"10.1542\/peds.2010-0442","article-title":"Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma","volume":"127","author":"Camargo","year":"2011","journal-title":"Pediatrics"},{"key":"2026021122414460600_bib6","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1164\/rccm.200808-1361OC","article-title":"Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica","volume":"179","author":"Brehm","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021122414460600_bib7","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1164\/rccm.201202-0351OC","article-title":"The effect of vitamin D and inhaled corticosteroid treatment on lung function in children","volume":"186","author":"Wu","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021122414460600_bib8","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1097\/EDE.obo13e318280dd5e","article-title":"Prospective association of 25-hydroxyvitamin d3 and d2 with childhood lung function, asthma, wheezing, and flexural dermatitis","volume":"24","author":"Tolppanen","year":"2013","journal-title":"Epidemiology"},{"key":"2026021122414460600_bib9","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1093\/jn\/131.11.2910","article-title":"The amino bisphosphonate ibandronate prevents vitamin D toxicity and inhibits vitamin D\u2013induced calcification of arteries, cartilage, lungs and kidneys in rats","volume":"131","author":"Price","year":"2001","journal-title":"J Nutr"},{"key":"2026021122414460600_bib10","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1177\/000348949210100403","article-title":"Pediatric tracheobronchomalacia and major airway collapse","volume":"101","author":"Mair","year":"1992","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"2026021122414460600_bib11","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s12098-011-0595-6","article-title":"Indications and outcome of flexible bronchoscopy in neonates","volume":"79","author":"Vijayasekaran","year":"2012","journal-title":"Indian J Pediatr"},{"key":"2026021122414460600_bib12","doi-asserted-by":"crossref","first-page":"F290","DOI":"10.1136\/adc.2004.062604","article-title":"Computed tomography versus bronchography in the diagnosis and management of tracheobronchomalacia in ventilator dependent infants","volume":"90","author":"Mok","year":"2005","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"issue":"4","key":"2026021122414460600_bib13","first-page":"CD005304","article-title":"Interventions for primary (intrinsic) tracheomalacia in children","author":"Masters","year":"2005","journal-title":"Cochrane Database Syst Rev"},{"key":"2026021122414460600_bib14","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.4049\/jimmunol.180.8.5211","article-title":"1\u03b1,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-\u03b2","volume":"180","author":"Taher","year":"2008","journal-title":"J Immunol"},{"key":"2026021122414460600_bib15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jsbmb.2004.03.054","article-title":"1,25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase","volume":"89-90","author":"Nguyen","year":"2004","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026021122414460600_bib16","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/j.1476-5381.2009.00428.x","article-title":"Vitamin D inhibits growth of human airway smooth muscle cells through growth factor\u2013induced phosphorylation of retinoblastoma protein and checkpoint kinase 1","volume":"158","author":"Damera","year":"2009","journal-title":"Br J Pharmacol"},{"key":"2026021122414460600_bib17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0378-3782(95)01719-4","article-title":"Vitamin D deficiency and fetal growth","volume":"45","author":"Brunvand","year":"1996","journal-title":"Early Hum Dev"},{"key":"2026021122414460600_bib18","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/jbmr.2081","article-title":"Identification of the vitamin D receptor in osteoblasts and chondrocytes but not osteoclasts in mouse bone","volume":"29","author":"Wang","year":"2014","journal-title":"J Bone Min Res"},{"key":"2026021122414460600_bib19","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1172\/JCI29463","article-title":"Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts","volume":"116","author":"Masuyama","year":"2006","journal-title":"J Clin Invest"},{"key":"2026021122414460600_bib20","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jsbmb.2014.01.002","article-title":"Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D\u2013deficiency","volume":"144","author":"Lam","year":"2014","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026021122414460600_bib21","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1164\/rccm.201203-0478OC","article-title":"The effect of Aspergillus fumigatus infection on vitamin D receptor expression in cystic fibrosis","volume":"186","author":"Coughlan","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026021122414460600_bib22","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00125-004-1329-3","article-title":"Vitamin D deficiency in early life accelerates type 1 diabetes in non-obese diabetic mice","volume":"47","author":"Giulietti","year":"2004","journal-title":"Diabetologia"},{"key":"2026021122414460600_bib23","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1002\/ar.20726","article-title":"Pulmonary architecture in the conducting regions of six rats","volume":"291","author":"Lee","year":"2008","journal-title":"Anat Rec (Hoboken)"},{"key":"2026021122414460600_bib24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.4103\/0971-6580.75851","article-title":"Clinicopathological studies on vitamin D(3) toxicity and therapeutic evaluation of Aloe vera in rats","volume":"18","author":"Chavhan","year":"2011","journal-title":"Toxicol Int"},{"key":"2026021122414460600_bib25","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1136\/thx.37.8.580","article-title":"The radial alveolar count method of Emery and Mithal: a reappraisal 2\u2014intrauterine and early postnatal lung growth","volume":"37","author":"Cooney","year":"1982","journal-title":"Thorax"},{"key":"2026021122414460600_bib26","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1002\/ar.20771","article-title":"An automated self-similarity analysis of the pulmonary tree of the Sprague-Dawley rat","volume":"291","author":"Einstein","year":"2008","journal-title":"Anat Rec (Hoboken)"},{"key":"2026021122414460600_bib27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1749-7922-6-35","article-title":"A technical modification for percutaneous tracheostomy: prospective case series study on one hundred patients","volume":"6","author":"Rezende-Neto","year":"2011","journal-title":"World J Emerg Surg"},{"key":"2026021122414460600_bib28","doi-asserted-by":"crossref","first-page":"834","DOI":"10.5811\/westjem.22550.9.22550","article-title":"Accuracy of a novel ultrasound technique for confirmation of endotracheal intubation by expert and novice emergency physicians","volume":"15","author":"Gottlieb","year":"2014","journal-title":"West J Emerg Med"},{"key":"2026021122414460600_bib29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/ppul.20549","article-title":"Sequential alterations of tracheal mechanical properties in the neonatal lamb: effect of mechanical ventilation","volume":"42","author":"Miller","year":"2007","journal-title":"Pediatr Pulmonol"},{"key":"2026021122414460600_bib30","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1113\/jphysiol.2008.150763","article-title":"Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator\u2013deficient mice","volume":"586","author":"Bonvin","year":"2008","journal-title":"J Physiol"},{"key":"2026021122414460600_bib31","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1210\/endo.132.4.8462452","article-title":"Direct effects of transforming growth factor-\u03b2 on chondrocytes are modulated by vitamin D metabolites in a cell maturation\u2013specific manner","volume":"132","author":"Schwartz","year":"1993","journal-title":"Endocrinology"},{"key":"2026021122414460600_bib32","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1007\/s10067-013-2432-y","article-title":"Does vitamin D affect femoral cartilage thickness? An ultrasonographic study","volume":"33","author":"Malas","year":"2014","journal-title":"Clin Rheumatol"},{"key":"2026021122414460600_bib33","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/ppul.22922","article-title":"Tracheomalacia is associated with lower FEV and Pseudomonas acquisition in children with CF","volume":"49","author":"Fischer","year":"2014","journal-title":"Pediatr Pulmonol"},{"key":"2026021122414460600_bib34","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1183\/09031936.00035111","article-title":"Malacia, inflammation and bronchoalveolar lavage culture in children with persistent respiratory symptoms","volume":"39","author":"De Baets","year":"2012","journal-title":"Eur Respir J"},{"key":"2026021122414460600_bib35","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1755-8794-6-47","article-title":"Vitamin D related genes in lung development and asthma pathogenesis","volume":"6","author":"Kho","year":"2013","journal-title":"BMC Med Genomics"},{"key":"2026021122414460600_bib36","doi-asserted-by":"crossref","first-page":"e167","DOI":"10.1542\/peds.2014-1860","article-title":"Vitamin D in fetal development: findings from a birth cohort study","volume":"135","author":"Hart","year":"2015","journal-title":"Pediatrics"},{"key":"2026021122414460600_bib37","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/0167-4889(94)90008-6","article-title":"Vitamin D stimulates DNA synthesis in alveolar type-II cells","volume":"1221","author":"Edelson","year":"1994","journal-title":"Biochim Biophys Acta"},{"key":"2026021122414460600_bib38","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/rr199","article-title":"Measuring the lung function in the mouse: the challenge of size","volume":"4","author":"Irvin","year":"2003","journal-title":"Respir Res"},{"key":"2026021122414460600_bib39","doi-asserted-by":"crossref","first-page":"e00276","DOI":"10.1002\/phy2.276","article-title":"Vitamin D deficiency causes airway hyperresponsiveness, increases airway smooth muscle mass, and reduces TGF-\u03b2 expression in the lungs of female BALB\/c mice","volume":"2","author":"Foong","year":"2014","journal-title":"Physiol Rep"},{"key":"2026021122414460600_bib40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3109\/02770903.2012.738269","article-title":"1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) attenuates airway remodeling in a murine model of chronic asthma","volume":"50","author":"Lai","year":"2013","journal-title":"J Asthma"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/56\/3\/383\/66830601\/ajrcmb_56_3_383.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/56\/3\/383\/66830601\/ajrcmb_56_3_383.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T03:47:36Z","timestamp":1770868056000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/56\/3\/383\/8467328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,1]]},"references-count":40,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3,1]]},"published-print":{"date-parts":[[2017,3,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2014-0482oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,3]]},"published":{"date-parts":[[2017,3,1]]}}}