Expression data from fetal sheep lung tissue (right lower lobe)
Ontology highlight
ABSTRACT:
ORGANISM(S): Ovis aries
PROVIDER: GSE87151 | GEO | 2016/09/22
SECONDARY ACCESSION(S): PRJNA343722
REPOSITORIES: GEO
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Project description:[Background] Antenatal steroid (ACS) therapy conveys lifesaving benefits to the preterm fetus. However, current treatments are associated with increased risk of growth, endocrine, and neurodevelopmental abnormalities. [Objectives] To inform ACS therapy optimisation we used a sheep model of pregnancy to test whether adverse fetal brain effects were independent of respiratory benefit and ACS pharmacokinetics. [Study Design] Ewes carrying a single fetus received intramuscular injections of either: i) 2 x 12mg dexamethasone phosphate 12 hourly (DexP) (Dex High); ii) 4 x 1.5mg DexP 12 hourly (Dex Low); iii) 1 x 0.125mg/kg betamethasone acetate (Beta-Acetate); or iv) Saline (Negative Control). Lambs were delivered for ventilation after 48 hours. Hippocampal and lung tissues were subjected to RNA sequencing. [Results] Dex High treatment did not mature the preterm ovine lung. Pulsatile (Dex High and Dex Low) treatments caused hippocampal RNA changes consistent with neuronal death. Constant, low-amplitude treatment (Beta Acetate) significantly improved lung function, with few adverse RNA transcriptional changes in the fetal hippocampus. [Conclusions] All ACS exposures caused significant alterations in fetal homeostasis. Pulsatile exposures caused dose-independent neurodegenerative changes in the fetal hippocampus. These data highlight the importance of considering magnitude, duration and stability of fetal glucocorticoid exposures in optimising ACS therapy.
2024-09-13 | GSE248786 | GEO
Project description:Purpose: Evaluated the transcriptional effects of an effective oral dosing of antental corticosteroids using betamethasone-phophate compared to the clinical treatment with the combination drug betamethasone-phosphate+betamethasone-acetate for fetal lung maturation. Methods: RNA-sequencing of the fetal hippocampus, liver and lung was done. Differential expression analysis was done using read counts. Results: There were no significant differences between oral Beta-P and the clinical treatment in the fetal hippocampus. Small differences were detected in the fetal lung associated with cellular proliferation and in the fetal liver. Conclusions: Oral betamethasone-phosphate is an effective oral treatment that does not cause toxic effect in the fetal brain despite the higher dose.
2019-09-25 | GSE131194 | GEO
Project description:ATAC-seq on human lower lobe of right lung For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2022-10-16 | GSE215567 | GEO
Project description:ATAC-seq on human lower lobe of right lung For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-03-30 | GSE170747 | GEO
Project description:RNA Evaluation human tissue W78 lower lobe of right lung microRNA-seq from Mortazavi For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-06-15 | GSE177658 | GEO
Project description:W78 lower lobe of right lung intact HIC For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2023-07-24 | GSE237921 | GEO
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.
2021-02-01 | GSE148645 | GEO
Project description:W78 lower lobe of right lung ENC4_83 For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2022-12-04 | GSE219689 | GEO
Project description:The late-gestation fetal lung has relatively high levels of expression of the mineralocorticoid receptor (MR) as well as the glucocorticoid receptor (GR), suggesting that endogenous corticosteroids may act in the lung through binding at MR as well as GR. This study was designed to determine the effects of physiologically relevant increases in steroids on MR and GR in the late-gestation lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both agonists were infused intravenously for 48 hours in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC and Na,K ATPase, and elastin and collagen content were determined at the end of the infusions. We found that aldosterone significantly reduced the initial airway pressures measured in situ during inflation. This effect did not occur with betamethasone alone or in combination with aldosterone. Conversely, betamethasone, but not aldosterone, significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs. Aldosterone altered novel gene pathways in the fetal lung, suggesting effects on lung compliance via genes which influence immune pathways and lung stiffness. The results are consistent with corticosteroid-induced fluid reabsorption at birth through GR rather than MR, but suggest that MR contributes effects facilitating lung inflation with the first breaths via nonclassical mechanisms. 4 sets of twin sheep fetuses at approximately 130d gestation (term is 147d) were used. One twin was infused with 0.2 mg aldosterone for 48 h, the other received vehicle.
2014-08-07 | E-GEOD-53048 | biostudies-arrayexpress
Project description:The late-gestation fetal lung has relatively high levels of expression of the mineralocorticoid receptor (MR) as well as the glucocorticoid receptor (GR), suggesting that endogenous corticosteroids may act in the lung through binding at MR as well as GR. This study was designed to determine the effects of physiologically relevant increases in steroids on MR and GR in the late-gestation lung. The GR agonist, betamethasone, the MR agonist, aldosterone, or both agonists were infused intravenously for 48 hours in ovine fetuses of approximately 130 days gestation. Effects on airway pressures during stepwise inflation of the in situ lung, expression of ENaC and Na,K ATPase, and elastin and collagen content were determined at the end of the infusions. We found that aldosterone significantly reduced the initial airway pressures measured in situ during inflation. This effect did not occur with betamethasone alone or in combination with aldosterone. Conversely, betamethasone, but not aldosterone, significantly increased expression of the epithelial sodium channel (ENaC) subunit mRNAs, and collagen and elastin content in the lungs. Aldosterone altered novel gene pathways in the fetal lung, suggesting effects on lung compliance via genes which influence immune pathways and lung stiffness. The results are consistent with corticosteroid-induced fluid reabsorption at birth through GR rather than MR, but suggest that MR contributes effects facilitating lung inflation with the first breaths via nonclassical mechanisms.
2014-08-07 | GSE53048 | GEO