Antenatal Endotoxin Induces Dysanapsis in Experimental Bronchopulmonary Dysplasia

Am J Respir Cell Mol Biol. 2024 Jan 11. doi: 10.1165/rcmb.2023-0157OC. Online ahead of print.ABSTRACTBronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is characterized by impaired lung development with sustained functional abnormalities due to alterations of airways and the distal lung. Although clinical studies have shown striking associations between antenatal stress and BPD, little is known about underlying pathogenetic mechanisms. Whether dysanapsis, the concept of discordant growth of airways and parenchyma, contributes to late respiratory disease due to antenatal stress is unknown. We hypothesized that antenatal endotoxin impairs juvenile lung function due to altered central airway and distal lung structure, suggesting the presence of dysanapsis in this preclinical BPD model. Fetal rats were exposed to intra-amniotic endotoxin (10 μg) or saline (controls) 2 days 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-CT. Lung function was assessed during invasive ventilation to quantify baseline mechanics, response to methacholine challenge, and spirometry. Endotoxin-exposed pups demonstrated distal lung simplification, decreased alveolar surface area, and decreased parenchymal-airway attachments. Endotoxin-exposed pups demonstrated decreased tracheal, 2nd, and 3rd...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Source Type: research