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

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; Denvir, M A

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

Citation

Wilson, K. S., Baily, J., Tucker, C. S., Matrone, G., Vass, S., Moran, C., …Denvir, M. A. (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, 120-131. https://doi.org/10.1016/j.mce.2015.07.025

• Journal Article Type: Article
• Acceptance Date: Jul 24, 2015
• Online Publication Date: Jul 26, 2015
• Publication Date: Oct 15, 2015
• Deposit Date: Sep 21, 2016
• Journal: Molecular and Cellular Endocrinology
• Print ISSN: 0303-7207
• Electronic ISSN: 1872-8057
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 414
• Pages: 120-131
• DOI: https://doi.org/10.1016/j.mce.2015.07.025
• Keywords: Zebrafish, heart, glucocorticoids, development, echocardiography,
• Public URL: http://researchrepository.napier.ac.uk/Output/369616