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Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

Wilson KS, Baily J, Tucker CS, Matrone G, Vass S, Moran C, Chapman KE, Mullins JJ, Kenyon C, Hadoke PW, Denvir MA - Mol. Cell. Endocrinol. (2015)

Bottom Line: GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls.GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls.Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

View Article: PubMed Central - PubMed

Affiliation: The British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.

No MeSH data available.


Related in: MedlinePlus

Effects of glucocorticoid manipulation on development, structure and function of the embryonic heart Structural and functional observations of embryonic hearts were carried over 120 h post fertilization (hpf) using Tg (CMLC2:GFP) zebrafish which had been exposed to the glucocorticoid receptor (GR) agonist dexamethasone (Dex) [100 μM] for 120 h or treated with targeted GR translational blocking morpholino (GR Mo). Results were compared with controls which are a mean of Dex (vehicle only) controls and GR Mo (mism Mo) controls. Parameters investigated were A) Inflow/outflow area (measured at 72 hpf), an indicator of cardiac looping from cardiac tube to two chambered heart, B) ventricular area, a marker of cardiac growth and development, C) cardiomyocyte number normalized to heart length, D) heart rate, E) stroke volume and F) cardiac output. Data are mean ± SEM and were compared to control by one-way ANOVA and Dunnett's post hoc test. A) inflow/outflow distance n = (20 ***p ≤ 0.0001, B) ventricle area n = 4 experiments, (6 hearts per experiment) ± SEM *P ≤ 0.05, **P ≤ 0.001, C) ventricle cardiomyocyte number (normalized to body length) n = 12 hearts *p ≤ 0.05, **p ≤ 0.01. D–F), all cardiac function assessments n = 4 experiments (12 embryos per experiment) *p ≤ 0.05.
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fig2: Effects of glucocorticoid manipulation on development, structure and function of the embryonic heart Structural and functional observations of embryonic hearts were carried over 120 h post fertilization (hpf) using Tg (CMLC2:GFP) zebrafish which had been exposed to the glucocorticoid receptor (GR) agonist dexamethasone (Dex) [100 μM] for 120 h or treated with targeted GR translational blocking morpholino (GR Mo). Results were compared with controls which are a mean of Dex (vehicle only) controls and GR Mo (mism Mo) controls. Parameters investigated were A) Inflow/outflow area (measured at 72 hpf), an indicator of cardiac looping from cardiac tube to two chambered heart, B) ventricular area, a marker of cardiac growth and development, C) cardiomyocyte number normalized to heart length, D) heart rate, E) stroke volume and F) cardiac output. Data are mean ± SEM and were compared to control by one-way ANOVA and Dunnett's post hoc test. A) inflow/outflow distance n = (20 ***p ≤ 0.0001, B) ventricle area n = 4 experiments, (6 hearts per experiment) ± SEM *P ≤ 0.05, **P ≤ 0.001, C) ventricle cardiomyocyte number (normalized to body length) n = 12 hearts *p ≤ 0.05, **p ≤ 0.01. D–F), all cardiac function assessments n = 4 experiments (12 embryos per experiment) *p ≤ 0.05.

Mentions: Ventricle inflow: outflow distance (IOD), a measure of the degree of cardiac looping during development, was increased at 72 hpf in GR Mo treated embryos suggesting delayed heart development (Fig. 2A). Ventricles from GR Mo treated embryos showed reduced cross-sectional area compared to controls (Fig. 2B) and reduced number of ventricular cardiomyocytes per unit heart volume (Fig. 2C). Heart rate and cardiac output were reduced in GR Mo embryos (Fig. 2D and F). In Dex-treated embryos, ventricle inflow: outflow distance was not different from controls (Fig. 2A), cross-sectional area was increased (Fig. 2B) and number of cardiomyocytes per unit heart volume was reduced compared to controls (Fig. 2C). Dex-treated embryos had similar heart rates but greater stroke volume and greater cardiac output compared to controls (Fig. 2D–F).


Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

Wilson KS, Baily J, Tucker CS, Matrone G, Vass S, Moran C, Chapman KE, Mullins JJ, Kenyon C, Hadoke PW, Denvir MA - Mol. Cell. Endocrinol. (2015)

Effects of glucocorticoid manipulation on development, structure and function of the embryonic heart Structural and functional observations of embryonic hearts were carried over 120 h post fertilization (hpf) using Tg (CMLC2:GFP) zebrafish which had been exposed to the glucocorticoid receptor (GR) agonist dexamethasone (Dex) [100 μM] for 120 h or treated with targeted GR translational blocking morpholino (GR Mo). Results were compared with controls which are a mean of Dex (vehicle only) controls and GR Mo (mism Mo) controls. Parameters investigated were A) Inflow/outflow area (measured at 72 hpf), an indicator of cardiac looping from cardiac tube to two chambered heart, B) ventricular area, a marker of cardiac growth and development, C) cardiomyocyte number normalized to heart length, D) heart rate, E) stroke volume and F) cardiac output. Data are mean ± SEM and were compared to control by one-way ANOVA and Dunnett's post hoc test. A) inflow/outflow distance n = (20 ***p ≤ 0.0001, B) ventricle area n = 4 experiments, (6 hearts per experiment) ± SEM *P ≤ 0.05, **P ≤ 0.001, C) ventricle cardiomyocyte number (normalized to body length) n = 12 hearts *p ≤ 0.05, **p ≤ 0.01. D–F), all cardiac function assessments n = 4 experiments (12 embryos per experiment) *p ≤ 0.05.
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fig2: Effects of glucocorticoid manipulation on development, structure and function of the embryonic heart Structural and functional observations of embryonic hearts were carried over 120 h post fertilization (hpf) using Tg (CMLC2:GFP) zebrafish which had been exposed to the glucocorticoid receptor (GR) agonist dexamethasone (Dex) [100 μM] for 120 h or treated with targeted GR translational blocking morpholino (GR Mo). Results were compared with controls which are a mean of Dex (vehicle only) controls and GR Mo (mism Mo) controls. Parameters investigated were A) Inflow/outflow area (measured at 72 hpf), an indicator of cardiac looping from cardiac tube to two chambered heart, B) ventricular area, a marker of cardiac growth and development, C) cardiomyocyte number normalized to heart length, D) heart rate, E) stroke volume and F) cardiac output. Data are mean ± SEM and were compared to control by one-way ANOVA and Dunnett's post hoc test. A) inflow/outflow distance n = (20 ***p ≤ 0.0001, B) ventricle area n = 4 experiments, (6 hearts per experiment) ± SEM *P ≤ 0.05, **P ≤ 0.001, C) ventricle cardiomyocyte number (normalized to body length) n = 12 hearts *p ≤ 0.05, **p ≤ 0.01. D–F), all cardiac function assessments n = 4 experiments (12 embryos per experiment) *p ≤ 0.05.
Mentions: Ventricle inflow: outflow distance (IOD), a measure of the degree of cardiac looping during development, was increased at 72 hpf in GR Mo treated embryos suggesting delayed heart development (Fig. 2A). Ventricles from GR Mo treated embryos showed reduced cross-sectional area compared to controls (Fig. 2B) and reduced number of ventricular cardiomyocytes per unit heart volume (Fig. 2C). Heart rate and cardiac output were reduced in GR Mo embryos (Fig. 2D and F). In Dex-treated embryos, ventricle inflow: outflow distance was not different from controls (Fig. 2A), cross-sectional area was increased (Fig. 2B) and number of cardiomyocytes per unit heart volume was reduced compared to controls (Fig. 2C). Dex-treated embryos had similar heart rates but greater stroke volume and greater cardiac output compared to controls (Fig. 2D–F).

Bottom Line: GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls.GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls.Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

View Article: PubMed Central - PubMed

Affiliation: The British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh EH16 4TJ, UK.

No MeSH data available.


Related in: MedlinePlus