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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 embryonic heart genes Relative mRNA abundance was determined in isolated hearts at 120 h post fertilization (hpf) after 120 h glucocorticoid receptor (GR) manipulation with either dexamethasone (Dex) [100 μM] or targeted gr morpholino (GR Mo). Genes which were investigated were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf) (C) ventricular myosin heavy chain (vmhc) (D) phospholamban (plb) (E) Ryanadine 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). mRNA expression was determined from isolated hearts at 120 hpf normalized to house-keeping gene, data are mean of n = 3 (150 hearts per n) ± SEM *p ≤ 0.05, **p ≤ 0.01. All data were compared to their controls by one-way ANOVA and Dunnett's post hoc test.
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fig4: Effects of glucocorticoid manipulation on embryonic heart genes Relative mRNA abundance was determined in isolated hearts at 120 h post fertilization (hpf) after 120 h glucocorticoid receptor (GR) manipulation with either dexamethasone (Dex) [100 μM] or targeted gr morpholino (GR Mo). Genes which were investigated were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf) (C) ventricular myosin heavy chain (vmhc) (D) phospholamban (plb) (E) Ryanadine 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). mRNA expression was determined from isolated hearts at 120 hpf normalized to house-keeping gene, data are mean of n = 3 (150 hearts per n) ± SEM *p ≤ 0.05, **p ≤ 0.01. All data were compared to their controls by one-way ANOVA and Dunnett's post hoc test.

Mentions: Genes associated with growth and maturity (igf, mef2c and vmhc) were affected by GR manipulation in isolated embryonic (120 hpf) hearts (Fig. 4). No alteration in expression was observed for gr mRNA in either the Dex or GR Mo groups (Fig. 4A). Isolated hearts from GR Mo embryos however displayed reduced expression of vmhc and igf mRNA; in contrast Dex-treated embryos showed increased levels of vmhc and igf compared to controls (Fig. 4B and C). Phospholamban (plb) mRNA expression was found to be decreased in hearts isolated from Dex-treated embryos compared to their controls (Fig. 4D) however no change was noted in these hearts for other genes associated with calcium handling (sarco-endoplasmic reticulum calcium transport ATPase (serca) the ryanodine release channel gene (ryr) (Fig. 4E and F). While the ryr expression was lower in GR Mo embryos there was no difference in other genes associated with calcium handling proteins (Fig. 4D–F). mef2c expression was found to be lower in hearts isolated from GR Mo compared to controls, Dex-treatment had no impact on the expression of this gene (Fig. 4G). Neither GR Mo nor Dex treatment were found to alter the expression of gata4 or nkx2.5 (Fig. 4H 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 glucocorticoid manipulation on embryonic heart genes Relative mRNA abundance was determined in isolated hearts at 120 h post fertilization (hpf) after 120 h glucocorticoid receptor (GR) manipulation with either dexamethasone (Dex) [100 μM] or targeted gr morpholino (GR Mo). Genes which were investigated were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf) (C) ventricular myosin heavy chain (vmhc) (D) phospholamban (plb) (E) Ryanadine 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). mRNA expression was determined from isolated hearts at 120 hpf normalized to house-keeping gene, data are mean of n = 3 (150 hearts per n) ± SEM *p ≤ 0.05, **p ≤ 0.01. All data were compared to their controls by one-way ANOVA and Dunnett's post hoc test.
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fig4: Effects of glucocorticoid manipulation on embryonic heart genes Relative mRNA abundance was determined in isolated hearts at 120 h post fertilization (hpf) after 120 h glucocorticoid receptor (GR) manipulation with either dexamethasone (Dex) [100 μM] or targeted gr morpholino (GR Mo). Genes which were investigated were (A) Glucocorticoid receptor (gr) (B) Insulin like growth factor (igf) (C) ventricular myosin heavy chain (vmhc) (D) phospholamban (plb) (E) Ryanadine 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). mRNA expression was determined from isolated hearts at 120 hpf normalized to house-keeping gene, data are mean of n = 3 (150 hearts per n) ± SEM *p ≤ 0.05, **p ≤ 0.01. All data were compared to their controls by one-way ANOVA and Dunnett's post hoc test.
Mentions: Genes associated with growth and maturity (igf, mef2c and vmhc) were affected by GR manipulation in isolated embryonic (120 hpf) hearts (Fig. 4). No alteration in expression was observed for gr mRNA in either the Dex or GR Mo groups (Fig. 4A). Isolated hearts from GR Mo embryos however displayed reduced expression of vmhc and igf mRNA; in contrast Dex-treated embryos showed increased levels of vmhc and igf compared to controls (Fig. 4B and C). Phospholamban (plb) mRNA expression was found to be decreased in hearts isolated from Dex-treated embryos compared to their controls (Fig. 4D) however no change was noted in these hearts for other genes associated with calcium handling (sarco-endoplasmic reticulum calcium transport ATPase (serca) the ryanodine release channel gene (ryr) (Fig. 4E and F). While the ryr expression was lower in GR Mo embryos there was no difference in other genes associated with calcium handling proteins (Fig. 4D–F). mef2c expression was found to be lower in hearts isolated from GR Mo compared to controls, Dex-treatment had no impact on the expression of this gene (Fig. 4G). Neither GR Mo nor Dex treatment were found to alter the expression of gata4 or nkx2.5 (Fig. 4H 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