Abstract
In this study we have assessed the effects of increased cortisol levels during early embryonic development on immune function in zebrafish (Danio rerio) larvae. Fertilized eggs were exposed to either a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor selectively) or a control medium for 6 h post-fertilization (0–6 hpf). First, we measured baseline expression of a number of immune-related genes (socs3a, mpeg1.1, mpeg1.2, and irg1l) 5 days post-fertilization (dpf) in larvae of the AB and TL strain to assess the effectiveness of our exposure procedure and potential strain differences. Cortisol and dexamethasone strongly up-regulated baseline expression of these genes independent of strain. The next series of experiments were therefore carried out in larvae of the AB strain only. We measured neutrophil/macrophage recruitment following tail fin amputation (performed at 3 dpf) and phenotypical changes as well as survival following LPS-induced sepsis (150 μg/ml; 4–5 dpf). Dexamethasone, but not cortisol, exposure at 0–6 hpf enhanced neutrophil recruitment 4 h post tail fin amputation. Cortisol and dexamethasone exposure at 0–6 hpf led to a milder phenotype (e.g., less tail fin damage) and enhanced survival following LPS challenge compared to control exposure. Gene-expression analysis showed accompanying differences in transcript abundance of tlr4bb, cxcr4a, myd88, il1β, and il10. These data show that early-life exposure to cortisol, which may be considered to be a model or proxy of maternal stress, induces an adaptive response to immune challenges, which seems mediated via the glucocorticoid receptor.
Highlights
In teleosts, like zebrafsh (Danio rerio), cortisol is the main endogenous corticosteroid, which is secreted when individuals perceive situations as stressful [1]
Since the glucocorticoid receptor (GR) has a lower affinity for cortisol than the mineralocorticoid receptor (MR), the GR mediates the actions of cortisol during stress, which involves optimizing energy expenditure by tuning the balance between and within physiological systems, like an organism’s metabolism and its immune, cardiovascular and central
These cortisol levels may reflect the allostatic load that the mothers experience in their environment and it has been hypothesized that these deposited cortisol levels are important for preparing the offspring for the expected allostatic load that larvae will encounter in the prevailing environment, thereby programming their cortisol secretion and the functioning of physiological systems to meet expected demands [4, 10]
Summary
Like zebrafsh (Danio rerio), cortisol is the main endogenous corticosteroid, which is secreted when individuals perceive situations as stressful [1]. Cortisol has been shown to signal through the GR already during the very early stages of embryonic development; in oocytes maternally deposited cortisol and GR mRNA are present [7,8,9]. These cortisol levels may reflect the allostatic load that the mothers experience in their environment and it has been hypothesized that these deposited cortisol levels are important for preparing the offspring for the expected allostatic load that larvae will encounter in the prevailing environment, thereby programming their cortisol secretion and the functioning of physiological systems to meet expected demands [4, 10]. Cortisol exposure may be considered to be a model or proxy of maternal stress [10, 13,14,15]
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