Effects of early life glucocorticoid exposure on metabolism in zebrafish (Danio rerio) larvae

Abstract

In this study we assessed the effects of increased cortisol levels during early embryonic development (0-6 hours post-fertilisation (hpf)), thereby mimicking maternal stress, on metabolism in zebrafish (Danio rerio) larvae. In two series of experiments fertilized eggs were exposed to a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor (GR) specifically) or a control medium for 6 hours post-fertilisation (0-6 hpf). In the first series we measured oxygen consumption as a proxy for metabolism, in the second series gene-expression of genes related to gluconeogenesis and glucose transport. Previously we have found that at 5 days post-fertilisation (dpf) baseline cortisol levels are increased following cortisol pre-treatment but not following dexamethasone pre-treatment, suggesting a higher hypothalamus-pituitary-interrenal cells (HPI-axis) activity. Hence, we hypothesized that oxygen consumption and gene-expression were stronger in cortisol-treated than in dexamethasone-treated and control-treated subjects at 5 dpf. Indeed, we observed increased oxygen consumption in cortisol-treated subjects compared to dexamethasone-treated or control-treated subjects. However, gene-expression levels were not different between treatments, which may have been due to a developmental delay in this second series. We also reasoned that both cortisol-treated and dexamethasone-treated subjects would show a higher metabolism at 1 dpf than control-treated subjects as the HPI-axis is not functional as yet and more general processes are being stimulated by cortisol through GR stimulation. Indeed, we observed increased oxygen consumption and increased expression of genes related to gluconeogenesis and glucose transport in cortisol-treated and dexamethasone-treated subjects than control-treated subjects. These data show that early-life exposure to cortisol, mimicking thereby maternal stress, increased metabolism at different life stages, i.e. 1 and 5 dpf, involving the GR.