Fetal lung maturation induced by chorioamnionitis and its interaction with antenatal corticosteroids in rhesus macaque fetuses
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ABSTRACT:
PROVIDER: PRJNA625272 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11544539_1.fastq.gz | Fastqsanger.gz | |||
| SRR11544539_2.fastq.gz | Fastqsanger.gz | |||
| SRR11544540_1.fastq.gz | Fastqsanger.gz | |||
| SRR11544540_2.fastq.gz | Fastqsanger.gz | |||
| SRR11544541_1.fastq.gz | Fastqsanger.gz |
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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.
2021-02-01 | GSE148645 | GEO
Project description:Oral dosing for antenatal corticosteroids in the rhesus macaque
| PRJNA542881 | ENA
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:We used single-nuclei sequencign to determine the effect of chorioamnionitis to the developing cerebellum using a rhesus macaque model of chorioamnionitis induced by intra-amniotic LPS.
2024-01-17 | GSE205001 | GEO
Project description:Chorioamnionitis is associated with preterm delivery and involution of the fetal thymus. Women at risk of preterm delivery receive antenatal corticosteroids which accelerate fetal lung maturation and improve neonatal outcome. However, the effects of antenatal corticosteroids on the fetal thymus in the settings of chorioamnionitis are largely unknown. We hypothesized that intra-amniotic exposure to lipopolysaccharide (LPS) causes involution of the fetal thymus resulting in persistent effects on thymic structure and cell populations. We also hypothesized that antenatal corticosteroids may modulate the effects of LPS on thymic development.Time-mated ewes with singleton fetuses received an intra-amniotic injection of LPS 7 or 14 days before preterm delivery at 120 days gestational age (term?=?150 days). LPS and corticosteroid treatment groups received intra-amniotic LPS either preceding or following maternal intra-muscular betamethasone. Gestation matched controls received intra-amniotic and maternal intra-muscular saline. The fetal intra-thoracic thymus was evaluated.Intra-amniotic LPS decreased the cortico-medullary (C/M) ratio of the thymus and increased Toll-like receptor (TLR) 4 mRNA and CD3 expression indicating involution and activation of the fetal thymus. Increased TLR4 and CD3 expression persisted for 14 days but Foxp3 expression decreased suggesting a change in regulatory T-cells. Sonic hedgehog and bone morphogenetic protein 4 mRNA, which are negative regulators of T-cell development, decreased in response to intra-amniotic LPS. Betamethasone treatment before LPS exposure attenuated some of the LPS-induced thymic responses but increased cleaved caspase-3 expression and decreased the C/M ratio. Betamethasone treatment after LPS exposure did not prevent the LPS-induced thymic changes.Intra-amniotic exposure to LPS activated the fetal thymus which was accompanied by structural changes. Treatment with antenatal corticosteroids before LPS partially attenuated the LPS-induced effects but increased apoptosis in the fetal thymus. Corticosteroid administration after the inflammatory stimulus did not inhibit the LPS effects on the fetal thymus.
| S-EPMC3365024 | biostudies-literature
Project description:Preterm premature rupture of membranes (PPROM), which precedes approximately 30–40% of preterm births, is the main cause of neonatal morbidity, mortality, and long-term sequelae. In particular, almost half of all PPRPM cases are frequently complicated by subclinical acute inflammation in the placenta and fetal tissue, commonly named as acute histologic chorioamnionitis [HCA]. Increasing evidences suggest that HCA carries additional risks to both the pregnant women and their fetuses, including greater risk of imminent preterm birth, as well as sepsis, neurologic morbidity, and mortality in neonates. More accurate and early prenatal predictive markers (especially noninvasive ones) are urgently needed for identifying subclinical HCA in the context of PPROM.To identify potential biomarkers in the plasma that could predict histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM), using shotgun and targeted proteomic analyses.
2022-08-12 | PXD027573 | Pride
Project description:Purpose: Evaluate fetal lung maturation and transcriptome after clinical treatment with antenatal corticosteroids compared to an alternative treatment with a slow release low-dose formulation. Methods: Lung mRNA profiles of rhesus macaques were generated by RNA sequencing. Reads that met quality thresholds were aligned to the rhesus macaque genome and number of reads per gene was counted. RNA-sequencing of the hippocampus was done. Differential expression analysis was done using read counts. Results: A relatively low dose of Beta-Ac increased lung compliance, surfactant concentration and relative airspace of the fetal lung equivalent to the clinical drug. By transcriptome analyses, the early suppression of genes associated with immune responses and the downregulation of genes associated with developmental pathways were less changed by Beta-Ac than the clinical drug. There were no significant differences between Beta-Ac and control while the clinical drug suppressed maturational pathways including genes involved in neurogenesis, neuronal differentiation and stem cell fate commitment. Conclusions: We report that low-dose betamethasone-acetate has decreased impact on lung transcriptome compared to the clinical treatment.
2019-06-21 | GSE118438 | GEO
Project description:To identify candidate miRNAs in amniotic fluids as biomarkers for chorioamnionitis, we compared miRNA array data in amniotic fluids between pregnant women with the absence and presence of histological chorioamnionitis.
2021-02-01 | GSE143193 | GEO
Project description:We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions.
2018-08-01 | GSE111927 | GEO
Project description:Chorioamnionitis and antenatal corticosteroids mature the fetal lung functionally but disrupt late-gestation lung development. Because Sonic Hedgehog (Shh) signaling is a major pathway directing lung development, we hypothesized that chorioamnionitis and antenatal corticosteroids modulated Shh signaling, resulting in an altered fetal lung structure. Time-mated ewes with singleton ovine fetuses received an intra-amniotic injection of lipopolysaccharide (LPS) and/or maternal intramuscular betamethasone 7 and/or 14 days before delivery at 120 days gestational age (GA) (term = 150 days GA). Intra-amniotic LPS exposure decreased Shh mRNA levels and Gli1 protein expression, which was counteracted by both betamethasone pre- or posttreatment. mRNA and protein levels of fibroblast growth factor 10 and bone morphogenetic protein 4, which are important mediators of lung development, increased 2-fold and 3.5-fold, respectively, 14 days after LPS exposure. Both 7-day and 14-day exposure to LPS changed the mRNA levels of elastin (ELN) and collagen type I alpha 1 (Col1A1) and 2 (Col1A2), which resulted in fewer elastin foci and increased collagen type I deposition in the alveolar septa. Corticosteroid posttreatment prevented the decrease in ELN mRNA and increased elastin foci and decreased collagen type I deposition in the fetal lung. In conclusion, fetal lung exposure to LPS was accompanied by changes in key modulators of lung development resulting in abnormal lung structure. Betamethasone treatment partially prevented the changes in developmental processes and lung structure. This study provides new insights into clinically relevant prenatal exposures and fetal lung development.
| S-EPMC3517680 | biostudies-literature