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

Stephen K. Wilson, J. Baily, Carl S Tucker, G. Matrone, S. Vass, C. Moran, K. E. Chapman, John J Mullins, C. Kenyon, P. W.F. Hadoke, Martin A Denvir

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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 k nockdown (GR Mo) over the first 120h post fertilisation (hpf); surviving embryos ( > 90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120hpf) and adult (120days post fertilisation (dpf)) hearts.GR Mo embryos (120hpf) 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 120hpf (Dex 107.2±3.1 vs. controls 90.2±1.1μm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62±0.13cells/μm vs control 2.18±0.13cells/μm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02±0.07μg/mg vs controls 0.63±0.06μg/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.
Original languageEnglish (US)
Pages (from-to)120-131
Number of pages12
JournalMolecular and cellular endocrinology
Volume414
DOIs
StatePublished - Oct 5 2015

Keywords

  • Development
  • Echocardiography
  • Glucocorticoids
  • Heart
  • Zebrafish

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