Environmental co-exposure of high temperature and Cu induce hormonal disturbance of cortisol signaling and altered responses of cellular defense genes in zebrafish

Global warming is causing a continuous increase in environmental temperatures, which simultaneously activates toxic environmental stresses, such as heavy metal exposure, in aquatic ecosystems. The present study aimed at evaluating the effects of Cu toxicity along with increased temperature during zebrafish embryogenesis. Decreased survival rates were observed following combined exposure to high temperature and Cu. Heart rates of zebrafish embryos were significantly increased only during heat stress. An abnormal morphology with curved body shape was induced by exposure to a combination of Cu and heat stress. Furthermore, heat stress also triggered Cu-induced intracellular reactive oxygen species (ROS) production, with upregulation of superoxide dismutase (SOD) and glutathione s-transferase (GST) expression, and cell death with modified expression of p53 and B-cell lymphoma-2 (Bcl-2) in zebrafish embryos. Finally, increased cortisol levels and altered expression of cortisol-signaling genes were observed following exposure to Cu and high temperatures. These results highlight that realistic exposure to combined stressors induces developmental disturbances via stress-induced responses involving oxidative stress and cell death as well as transcriptional alterations leading to cortisol signaling in fish. • Effects of increased temperature and Cu during zebrafish embryogenesis were studied. • An increase of abnormal morphology and mortality was observed. • An intracellular ROS production and induced cell death were observed in the live body. • Combined stressors induced alterations of cortisol level and cortisol-signaling genes. • Changes of cortisol signaling caused impacts on sex determination of fish embryos.