Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart
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 cessation of antenatal glucocorticoid exposure, irrespective of fetal genotype. The myocardial performance index and E/A wave ratio, markers of fetal heart maturation, were not significantly affected by dexamethasone treatment in either genotype. Dexamethasone 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 and 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 dexamethasone treatment upon the hypothalamic-pituitary-adrenal axis between genotypes. These data suggest potentially detrimental and direct effects of antenatal glucocorticoid treatment upon fetal heart function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:241 |
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| Enthalten in: |
The Journal of endocrinology - 241(2019), 3 vom: 01. Juni, Seite 279-292 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Agnew, E J [VerfasserIn] |
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| Links: |
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| Themen: |
7S5I7G3JQL |
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| Anmerkungen: |
Date Completed 30.12.2019 Date Revised 09.03.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1530/JOE-18-0666 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM296337005 |
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| 100 | 1 | |a Agnew, E J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 30.12.2019 | ||
| 500 | |a Date Revised 09.03.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 cessation of antenatal glucocorticoid exposure, irrespective of fetal genotype. The myocardial performance index and E/A wave ratio, markers of fetal heart maturation, were not significantly affected by dexamethasone treatment in either genotype. Dexamethasone 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 and 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 dexamethasone treatment upon the hypothalamic-pituitary-adrenal axis between genotypes. These data suggest potentially detrimental and direct effects of antenatal glucocorticoid treatment upon fetal heart function | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a cardiovascular | |
| 650 | 4 | |a corticosteroids | |
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| 650 | 4 | |a glucocorticoid receptor | |
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| 650 | 7 | |a RNA, Messenger |2 NLM | |
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| 700 | 1 | |a Garcia-Burgos, A |e verfasserin |4 aut | |
| 700 | 1 | |a Richardson, R V |e verfasserin |4 aut | |
| 700 | 1 | |a Manos, H |e verfasserin |4 aut | |
| 700 | 1 | |a Thomson, A J W |e verfasserin |4 aut | |
| 700 | 1 | |a Sooy, K |e verfasserin |4 aut | |
| 700 | 1 | |a Just, G |e verfasserin |4 aut | |
| 700 | 1 | |a Homer, N Z M |e verfasserin |4 aut | |
| 700 | 1 | |a Moran, C M |e verfasserin |4 aut | |
| 700 | 1 | |a Brunton, P J |e verfasserin |4 aut | |
| 700 | 1 | |a Gray, G A |e verfasserin |4 aut | |
| 700 | 1 | |a Chapman, K E |e verfasserin |4 aut | |
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