Effect of ~ 25 days cortisol treatment on late gestation fetal left ventricle
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA562441 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. In previous studies of the intraventricular septum from these fetuses we found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. We extended this investigation to the left ventricular free wall of these fetuses.le. Fewer genes were differentially regulated in left ventricle in the near term fetuses. In the LV of this cohort of fetuses, the nonredundant KEGG pathways represented by the DEG were insulin resistance and adipocytokine signaling pathway. GSEA analysis of the DEG in LV identified metabolic pathways as the nonredundant pathway altered. Comparison of the change in gene expression in biceps to that in cardiac intraventricular septum and left ventricle showed few common genes with little overlap in specific metabolic or signaling pathways, despite effects on mitochondria and metabolism in both heart and biceps. Our results suggest that glucocorticoid exposure affects nuclear genes important to mitochondrial activity and reactive oxygen in both cardiac and skeletal muscle tissues in a tissue specific manner.
2019-11-01 | GSE136315 | GEO
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, CushingM-bM-^@M-^Ys disease and chronic stress. 2 cohorts of singleton sheep fetuses at 129-131d gestation or 139-144d gestation (approximately term) were used. The first cohort received maternal cortisol infusion of 1mg/kg/day or vehicle for 10 days until approximately day 130 of gestation (n=6/group), the second cohort received the same dose of cortisol for approximately 25 days until near term (n=7, cortisol; n=7ewes, n=8 fetuses due to one set of twins, control)
2014-08-07 | E-GEOD-54237 | biostudies-arrayexpress
Project description:Previous studies have suggested that increases in maternal cortisol or maternal stress in late pregnancy increase the risk of stillbirth at term. In an ovine model with increased maternal cortisol over the last 0.20 of gestation, we have previously found evidence of disruption of fetal serum and cardiac metabolomics, and of expression of genes related to mitochondrial function and metabolism in biceps femoris, diaphragm and cardiac muscle. The present studies were designed to test for effects of chronically increased maternal cortisol on gene expression and metabolomics in placentomes near term. We hypothesized that changes in placenta may underlie or contribute to the alterations in fetal serum metabolomics, and thereby contribute to changes in striated muscle metabolism. Multi-omic analysis indicates that amino acid metabolism, particularly of branched chain amino acids and glutamate occur in placenta; changes in amino acid metabolism, degradation or biosynthesis in placenta were consistent changes in valine, isoleucine, leucine and glycine in fetal serum. The analysis also indicates changes in glycerophospholipid metabolism, and suggests changes in ER stress and antioxidant status in the placenta. These findings suggest that changes in placental function occurring with excess maternal cortisol in late gestation may contribute to metabolic dysfunction in the fetus at birth.
2020-09-01 | GSE149402 | GEO
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. In previous studies of the intraventricular septum from these fetuses we found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. To investigate the effects on skeletal muscle, we extended the transcriptomic analyses to biceps femoralis. Transcriptomic modelling revealed that pathways related to mitochondrial metabolism were downregulated, whereas pathways suggestive of positive regulation of reactive oxygen species and activation of the apoptotic cascade were upregulated. Mitochondrial DNA (mt-DNA) and the protein levels of cytochrome C was significantly decreased in the biceps. RT- PCR validation of the pathways showed significant decrease in SLC2A4 mRNA levels, and a significant increase in PDK4, TXNIP, ANGPTL4 mRNA levels, consistent with reduced insulin sensitivity of the bicep muscles. Comparison of the change in gene expression in biceps to that in cardiac intraventricular septum and left ventricle showed few common genes with little overlap in specific metabolic or signaling pathways, despite reduction in mitochondria in both heart and biceps. Our results suggest that glucocorticoid exposure affects nuclear genes important to mitochondrial activity and reactive oxygen in both cardiac and skeletal muscle tissues in a tissue specific manner.
2019-11-01 | GSE136384 | GEO
Project description:We have previously shown in sheep that 10 days of modest chronic increase in maternal cortisol result in fetal heart enlargement and Purkinje cell apoptosis. In subsequent studies in which we extended the duration of cortisol infusion (1mg/kg/d) to term, we found a dramatic incidence of stillbirth in the pregnancies with chronically increased cortisol and associated maternal hyperglycemia. To investigate the effects on the heart, transcriptomic analyses were performed on the septa using ovine microarrays and Webgestalt and Cytoscape programs for pathway inference. Analyses of the effects of 10 days of maternal cortisol infusion (130d-cortisol vs 130d control), ~25 days (term at ~140d-cortisol vs 140d control), normal maturation (140d-control vs 130d control) were performed. In all analyses gene ontology (GO) terms related to immune function and cytokine actions were significantly over-represented. After 10 days of cortisol, growth factor and muscle cell apoptosis pathways were significantly over-represented, consistent with our previous findings. We found significantly differentially regulated genes in the term fetuses (ie after ~25 days of cortisol) in pathways consistent with altered metabolism in the heart, particularly in mitochondria, associated with responses to hypoxia and to nutrient. Analysis of mitochondrial number by quantitative real-time PCR confirmed a significant decrease. These pathways were different from those modeled following the normal increase in cortisol in late gestation which contributes to normal maturation of the heart, and thus may be indicative of the fetal heart pathophysiologies seen in pregnancies complicated by diabetes, Cushing’s disease and chronic stress.
2014-08-07 | GSE54237 | GEO
Project description:Effect of ~ 25 days cortisol treatment on late gestation fetal
| PRJNA562439 | ENA
Project description:Effect of ~ 25 days cortisol treatment on late gestation placenta
| PRJNA628618 | ENA
Project description:Adult rabbit left ventricle RNAseq
| PRJNA475561 | ENA
Project description:Effect of ~ 25 days cortisol treatment on late gestation fetal biceps femoris
| PRJNA562442 | ENA
Project description:We have identified effects of elevated maternal cortisol on fetal cardiac maturation and function in an ovine model. Whereas short term exposure, produced by maternal infusion (1 mg/kg/d) from 115-130d gestation increased fetal heart wall thickness and weight, myocyte proliferation and Purkinje fiber apoptosis, when cortisol exposure continued until term (~145 days of gestation), there was a profound increase in perinatal stillbirth. Further study indicated increases in P-R and R-R interval of the ECG and increased incidence of arrhythmias at birth, suggesting that these changes in the fetal heart contribute to the stillbirth. We have used systems biology to statistically model the transcriptomic changes in hearts at 130 days and near term. In the current study, we used this approach to test for effects on pathways related to metabolism and cardiac structure in the left ventricle and septum from newborn lambs. Cortisol altered genes in pathways involved in cardiac architecture in the left ventricle, including SMAD and BMP; cortisol also increased collagen deposition. Genes in pathways involved in metabolism and actin filament assembly were affected within the septum. Comparison of the effects of cortisol to the effects of normal maturation from day 140 to birth revealed that only 1% of the genes changed by cortisol in the LV and 18% in the septum were consistent with the normal maturational changes in gene expression. These results indicate that chronic in utero exposure to elevated cortisol concentrations alters the normal maturation of the fetal myocardium, adversely impacting perinatal cardiac function.
2019-01-04 | GSE110470 | GEO