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| Status |
Public on Feb 01, 2021 |
| Title |
Fetal lung maturation induced by chorioamnionitis and its interaction with antenatal corticosteroids in rhesus macaque fetuses |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Time-pregnant rhesus macaques received intra-amniotic injection of LPS or the combination of intra-amniotic LPS plus intrumuscular corticosteroids and were delivered after 5 days. Another group of animals exposed to intra-amniotic LPS was delivered 16h after treatments
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| Contributor(s) |
Schmidt AF, Kannan PS, Pietro P, Courtney JM, Miller LA, Suhas KG, Claire CA, Jobe AH |
| Citation(s) |
33328385 |
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| Submission date |
Apr 14, 2020 |
| Last update date |
Feb 01, 2021 |
| Contact name |
Augusto F Schmidt |
| E-mail(s) |
aschmidt@med.miami.edu
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| Phone |
3052430156
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| Organization name |
University of Miami Miller School of Medicine
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| Street address |
1611 NW 12th ave
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| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
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| Platforms (1) |
| GPL23804 |
Illumina HiSeq 3000 (Macaca mulatta) |
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| Samples (16)
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| GSM4476076 |
Lung, 038 |
| GSM4476077 |
Lung, 092 |
| GSM4476078 |
Lung, 101 |
| GSM4476079 |
Lung, 113 |
| GSM4476080 |
Lung, 200 |
| GSM4476081 |
Lung, 201 |
| GSM4476082 |
Lung, 209 |
| GSM4476083 |
Lung, 239 |
| GSM4476084 |
Lung, 240 |
| GSM4476085 |
Lung, 242 |
| GSM4476086 |
Lung, 248 |
| GSM4476087 |
Lung, 249 |
| GSM4476088 |
Lung, 255 |
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| Relations |
| BioProject |
PRJNA625272 |
| SRA |
SRP256342 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148645_counts.csv.gz |
616.5 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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