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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 embryonic glucocorticoid receptor manipulation on adult heart gene expression mRNA expression in adult isolated hearts after glucocorticoid receptor (GR) manipulation with either GR agonist dexamethasone (Dex) [100 μM], or targeted GR knockdown using morpholino (GR Mo). Genes of interest were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf), (C) ventricular myosin heavy chain (vmhc), (D) phospholamban (plb), (E) Ryanodine receptor (ryr), (F) sarco-endoplasmic reticulum Ca2+ ATPase (serca), (G) myocyte enhancer factor 2 c (mef2c), (H) GATA transcription factor 4 (gata4) and (I) Homeobox protein NKX2.5 (nkx2.5). Relative mRNA expression was determined from isolated hearts at 120 dpf, mean of n = 3 (5 hearts per n) ± SEM, all data analysed compared to control by one-way ANOVA and Dunnett's post hoc test (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001).
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fig7: Effects of embryonic glucocorticoid receptor manipulation on adult heart gene expression mRNA expression in adult isolated hearts after glucocorticoid receptor (GR) manipulation with either GR agonist dexamethasone (Dex) [100 μM], or targeted GR knockdown using morpholino (GR Mo). Genes of interest were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf), (C) ventricular myosin heavy chain (vmhc), (D) phospholamban (plb), (E) Ryanodine receptor (ryr), (F) sarco-endoplasmic reticulum Ca2+ ATPase (serca), (G) myocyte enhancer factor 2 c (mef2c), (H) GATA transcription factor 4 (gata4) and (I) Homeobox protein NKX2.5 (nkx2.5). Relative mRNA expression was determined from isolated hearts at 120 dpf, mean of n = 3 (5 hearts per n) ± SEM, all data analysed compared to control by one-way ANOVA and Dunnett's post hoc test (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001).

Mentions: Ventricles from adults treated with Dex during embryonic development had increased expression of gr, vmhc and plb mRNA compared to controls (Fig. 7A, C and D respectively) but displayed reduced mef2c and ryr mRNA relative abundance compared to controls (Fig. 7I and G respectively). In adult ventricles derived from GR Mo embryos, mRNA levels of vmhc (Fig. 7C) and gata4 (Fig. 7H) were reduced compared to controls while plb and mef2c mRNA abundance was increased (Fig. 7D and G respectively). No alteration in gene abundance was observed for igf and nkx2.5 in either GR Mo or Dex treated embryos (Fig. 7B and I).


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 embryonic glucocorticoid receptor manipulation on adult heart gene expression mRNA expression in adult isolated hearts after glucocorticoid receptor (GR) manipulation with either GR agonist dexamethasone (Dex) [100 μM], or targeted GR knockdown using morpholino (GR Mo). Genes of interest were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf), (C) ventricular myosin heavy chain (vmhc), (D) phospholamban (plb), (E) Ryanodine receptor (ryr), (F) sarco-endoplasmic reticulum Ca2+ ATPase (serca), (G) myocyte enhancer factor 2 c (mef2c), (H) GATA transcription factor 4 (gata4) and (I) Homeobox protein NKX2.5 (nkx2.5). Relative mRNA expression was determined from isolated hearts at 120 dpf, mean of n = 3 (5 hearts per n) ± SEM, all data analysed compared to control by one-way ANOVA and Dunnett's post hoc test (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001).
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fig7: Effects of embryonic glucocorticoid receptor manipulation on adult heart gene expression mRNA expression in adult isolated hearts after glucocorticoid receptor (GR) manipulation with either GR agonist dexamethasone (Dex) [100 μM], or targeted GR knockdown using morpholino (GR Mo). Genes of interest were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf), (C) ventricular myosin heavy chain (vmhc), (D) phospholamban (plb), (E) Ryanodine receptor (ryr), (F) sarco-endoplasmic reticulum Ca2+ ATPase (serca), (G) myocyte enhancer factor 2 c (mef2c), (H) GATA transcription factor 4 (gata4) and (I) Homeobox protein NKX2.5 (nkx2.5). Relative mRNA expression was determined from isolated hearts at 120 dpf, mean of n = 3 (5 hearts per n) ± SEM, all data analysed compared to control by one-way ANOVA and Dunnett's post hoc test (*p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001).
Mentions: Ventricles from adults treated with Dex during embryonic development had increased expression of gr, vmhc and plb mRNA compared to controls (Fig. 7A, C and D respectively) but displayed reduced mef2c and ryr mRNA relative abundance compared to controls (Fig. 7I and G respectively). In adult ventricles derived from GR Mo embryos, mRNA levels of vmhc (Fig. 7C) and gata4 (Fig. 7H) were reduced compared to controls while plb and mef2c mRNA abundance was increased (Fig. 7D and G respectively). No alteration in gene abundance was observed for igf and nkx2.5 in either GR Mo or Dex treated embryos (Fig. 7B and I).

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