Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart

Autor: Karen E. Chapman, Carmel M. Moran, Adrian Garcia-Burgos, Paula J. Brunton, Natalie Z.M. Homer, Emma J Agnew, Hermes Manos, Karen Sooy, Adrian Thomson, George Just, Rachel V. Richardson, Gillian A. Gray
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Vascular smooth muscle
Endocrinology
Diabetes and Metabolism
Pituitary-Adrenal System
Endogeny
Dexamethasone
Muscle
Smooth
Vascular
corticosteroids
Mice
0302 clinical medicine
Endocrinology
Glucocorticoid receptor
Diastole
glucocorticoid receptor
Myocytes
Cardiac
reproductive and urinary physiology
cardiovascular
Embryo
Organ Size
3. Good health
Maternal Exposure
embryonic structures
Female
Glucocorticoid
medicine.drug
steroids
medicine.medical_specialty
Hypothalamo-Hypophyseal System
Genotype
embryo
03 medical and health sciences
Fetal Heart
Receptors
Glucocorticoid
Internal medicine
medicine
Animals
RNA
Messenger
Glucocorticoids
Fetus
business.industry
Research
Body Weight
Mice
Inbred C57BL
030104 developmental biology
business
030217 neurology & neurosurgery
Hormone
Zdroj: The Journal of Endocrinology
Agnew, E, Garcia-Burgos, A, Richardson, R, Manos, H, Thomson, A, Sooy, K, Just, G, Homer, N, Moran, C, Brunton, P J, Gray, G A & Chapman, K 2019, ' Antenatal dexamethasone treatment transiently alters diastolic function in the mouse fetal heart ', Journal of Endocrinology . https://doi.org/10.1530/JOE-18-0666
ISSN: 1479-6805
DOI: 10.1530/JOE-18-0666
Popis: 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.
Databáze: OpenAIRE
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