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

Wilson, K.S. et al. (2015) Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart. Molecular and Cellular Endocrinology, 414, pp. 120-131. (doi: 10.1016/j.mce.2015.07.025) (PMID:26219824) (PMCID:PMC4562295)

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Abstract

Background: Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. Methods and results: Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. 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. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/μm vs control 2.18 ± 0.13 cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 μg/mg vs controls 0.63 ± 0.06 μg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. Conclusion: Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

Item Type:Articles
Additional Information:This study was funded by a British Heart Foundation PhD Fellowship award (KW) grant number RE/09/053. The work was also supported by the British Heart Foundation Centre of Research Excellence award (CoRE) grant number RE/08/001/23904
Status:Published
Glasgow Author(s) Enlighten ID:Wilson, Dr Kathryn
Authors: Wilson, K.S., Baily, J., Tucker, C.S., Matrone, G., Vass, S., Moran, C., Chapman, K.E., Mullins, J.J., Kenyon, C., Hadoke, P.W.F., and Denvir, M.A.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:03037207
ISSN (Online):1872-8057
Published Online:26 July 2015
Copyright Holders:Copyright © 2015 The Author
First Published:First published in Molecular and Cellular Endocrinology: 414 (2015): 120-131
Publisher Policy:Reproduced under a creative commons license

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