| Autor: |
Agnew, E. J., Garcia-Burgos, A., Richardson, R. V., Manos, H., Thomson, A. J. W., Sooy, K., Just, G., Homer, N. Z. M., Moran, C. M., Brunton, P. J., Gray, G. A., Chapman, K. E. |
| Předmět: |
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| Zdroj: |
Journal of Endocrinology; Jun2019, Vol. 241 Issue 3, p279-292, 14p |
| Abstrakt: |
Endogenous glucocorticoid action is important in the structural and functional maturation of the fetal heart. In fetal mice, although glucocorticoid concentrations are extremely low before E14.5, glucocorticoid receptor (GR) is expressed in the heart from E10.5. To investigate whether activation of cardiac GR prior to E14.5 induces precocious fetal heart maturation, we administered dexamethasone in the drinking water of pregnant dams from E12.5 to E15.5. To test the direct effects of glucocorticoids upon the cardiovascular system we used SMGRKO mice, with Sm22-Cre-mediated disruption of GR in cardiomyocytes and vascular smooth muscle. Contrary to expectations, echocardiography showed no advancement of functional maturation of the fetal heart. Moreover, litter size was decreased 2 days following ces sation of antenatal glucocorticoid exposure, irrespective of fetal genotype. The myocardial performance index and E/A wave ratio, markers of fetal heart maturation, we re not significantly affected by dexamethasone treatment in either genotype. Dexameth asone treatment transiently decreased the myocardial deceleration index (MDI; a marker of diastolic function), in control fetuses at E15.5, with recovery by E17.5, 2 days after cessation of treatment. MDI was lower in SMGRKO than in control fetuses a nd was unaffected by dexamethasone. The transient decrease in MDI was associated with repression of cardiac GR in control fetuses following dexamethasone treatment. Measurement of glucocorticoid levels in fetal tissue and hypothalamic corticotropin-releasing hormone (Crh) mRNA levels suggest complex and differential effects of dexamet hasone treatment upon the hypothalamic-pituitary-adrenal axis between genotypes. These data suggest potentially detrimental and direct effects of antenatal glucocor ticoid treatment upon fetal heart function. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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