Single-nuclei sequencing of late gestation rhesus macaques exposed to chorioamnionitis
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE205001 | GEO | 2024/01/17
REPOSITORIES: GEO
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Project description:Purpose: Our goal was to evaluate the pathways through which chorioamnionitis induces fetal lung maturation and how it interacts with a low-dose treatment with antenatal corticosteroids to further enhance fetal lung maturation. Methods: We treated pregnant rhesus macaque at 132 days (80% gestation) with intre-amniotic bacterla lipopolissacharide to model chorioamnionitis or a low-dose antenatal corticosteroids treatment with betamethasone-acetate (Beta-Ac 0.125mg/kg) or both treatments. Fetuses were delivered by c-section after 5 days and RNA-sequencing of whole lung tissue was performed. Another group of fetuses exposed to LPS was delivered 16h after treatment. Preterm controls were delivered at 132 days and term controls were delivered at 155 days and received no intervention. Results: Treatment with Beta-Ac in the setting of chorioamnionitis improves lung compliance and increases surfactant production relative to either treatment alone. RNA sequencing shows that these changes are mediated by suppression of proliferation and induction of mesenchymal cellular death. The combined exposure results in a mature-like transcriptomic profile with inhibition of extracellular matrix development by suppression of collagen genes and regulators of lung development. ACS and inflammation also suppressed signature genes associated with proliferative mesenchymal progenitors similar to the term lung. Conclusion: Treatment with ACS in the setting of inflammation may result in early respiratory advantage to preterm infants, but this advantage may come at a cost of abnormal extracellular matrix development which may be associated with increased risk of chronic lung disease.
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