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Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about the underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of the airways and parenchyma, contributes to late respiratory disease as a result of antenatal stress is unknown. We hypothesized that antenatal endotoxin (ETX) impairs juvenile lung function as a result of altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intraamniotic ETX (10\u2009\u03bcg) or saline solution (control) 2\u2009days before term. We performed extensive structural and functional evaluation of the proximal airways and distal lung in 2-week-old rats. Distal lung structure was quantified by stereology. Conducting airway diameters were measured using micro\u2013computed tomography. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. ETX-exposed pups exhibited distal lung simplification, decreased alveolar surface area, and decreased parenchyma\u2013airway attachments. ETX-exposed pups exhibited decreased tracheal and second- and third-generation airway diameters. ETX increased respiratory system resistance and decreased lung compliance at baseline. Only Newtonian resistance, specific to large airways, exhibited increased methacholine reactivity in ETX-exposed pups compared with controls. ETX-exposed pups had a decreased ratio of FEV in 0.1\u2009second to FVC and a normal FEV in 0.1\u2009second, paralleling the clinical definition of dysanapsis. Antenatal ETX causes abnormalities of the central airways and distal lung growth, suggesting that dysanapsis contributes to abnormal lung function in juvenile rats.<\/jats:p>","DOI":"10.1165\/rcmb.2023-0157oc","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T14:35:30Z","timestamp":1704983730000},"page":"283-294","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":6,"title":["Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8828-2705","authenticated-orcid":false,"given":"Elizabeth A.","family":"McGinn","sequence":"first","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"},{"name":"Department of Pediatric Critical Care Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Bye","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Bilodeaux","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Seedorf","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1583-6762","authenticated-orcid":false,"given":"Bradford J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"},{"name":"Department of Pediatric Pulmonary and Sleep Medicine, and"},{"name":"Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7292-2085","authenticated-orcid":false,"given":"Steven H.","family":"Abman","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"},{"name":"Department of Pediatric Pulmonary and Sleep Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-7410","authenticated-orcid":false,"given":"Erica W.","family":"Mandell","sequence":"additional","affiliation":[{"name":"Pediatric Heart Lung Center, Department of Pediatrics"},{"name":"Department of Neonatology, University of Colorado School of Medicine, Aurora, Colorado; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,4,1]]},"reference":[{"key":"2026012204044673600_bib1","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/MOP.0b013e3283423e6b","article-title":"The new bronchopulmonary dysplasia","volume":"23","author":"Jobe","year":"2011","journal-title":"Curr Opin Pediatr"},{"key":"2026012204044673600_bib2","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1001\/jama.2015.10244","article-title":"Trends in care practices, morbidity, and mortality of extremely preterm neonates, 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