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| Status |
Public on Nov 01, 2019 |
| Title |
Effect of ~ 25 days cortisol treatment on late gestation fetal left ventricle |
| Organism |
Ovis aries |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Ewes carrying singleton sheep fetuses at 139-144d gestation (approximately term) were used. Ewes were either treated with 1 mg/kg/d of cortisol (Solu-Cortef) or vehicle starting on day 115 of pregnancy and continuing until the time of necropsy for tissue collection (n=7, cortisol; n=7 control ewes) . Ewes were sacrificed as soon as possible after the onset of labor.
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| Contributor(s) |
Joseph S, Richards EM, Antolic A, Wood CE, Keller-Wood M |
| Citation(s) |
32116114 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 HD057871 |
Effects of maternal cortisol on fetal and neonatal growth and metabolism |
UNIVERSITY OF FLORIDA |
Maureen Keller-Wood |
| R01 HD057871 |
Effects of maternal cortisol on fetal and neonatal growth and metabolism |
UNIVERSITY OF FLORIDA |
Maureen Keller-Wood |
|
| Submission date |
Aug 26, 2019 |
| Last update date |
Mar 10, 2020 |
| Contact name |
Maureen Keller-Wood |
| E-mail(s) |
kellerwd@cop.ufl.edu
|
| Organization name |
University of Florida
|
| Department |
Pharmacodynamics
|
| Lab |
Keller-Wood
|
| Street address |
1225 Center Dr
|
| City |
Gainesville |
| State/province |
Florida |
| ZIP/Postal code |
32610 |
| Country |
USA |
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| Platforms (1) |
| GPL10427 |
Agilent-019921 Sheep Gene Expression Microarray (Feature Number version) |
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| Samples (10)
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| GSM4044545 |
fetal left ventricle_control_140d_ replicate 1 |
| GSM4044546 |
fetal left ventricle_control_140d_ replicate 2 |
| GSM4044547 |
fetal left ventricle_control_140d_ replicate 3 |
| GSM4044548 |
fetal left ventricle_control_140d_ replicate 4 |
| GSM4044549 |
fetal left ventricle_control_140d_ replicate 5 |
| GSM4044550 |
fetal left ventricle_cortisol_140d_ replicate 1 |
| GSM4044551 |
fetal left ventricle_cortisol_140d_ replicate 2 |
| GSM4044552 |
fetal left ventricle_cortisol_140d_ replicate 3 |
| GSM4044553 |
fetal left ventricle_cortisol_140d_ replicate 4 |
| GSM4044554 |
fetal left ventricle_cortisol_140d_ replicate 5 |
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| This SubSeries is part of SuperSeries: |
| GSE136385 |
Effect of ~ 25 days cortisol treatment on late gestation fetal |
|
| Relations |
| BioProject |
PRJNA562441 |
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