Deoxycorticosterone acetate-induced acceleration of embryogenesis and oxidative and metabolic stresses in zebrafish

This study investigated the effects of environmentally relevant concentrations of deoxycorticosterone acetate (DOCA) on embryonic development and oxidative stress in zebrafish (Danio rerio), while also elucidating the underlying molecular mechanisms. Embryos were exposed to DOCA at 5, 50, and 500 ng/L, spanning both environmentally pertinent and elevated concentrations. Integrated morphological and transcriptomic analyses (RNA-seq and qRT-PCR) demonstrated dose-dependent acceleration of development, along with alterations in pigmentation, oxidative balance, and metabolic processes. At 50 ng/L, yolk extension increased by 43.3 %, whereas yolk sac area decreased by 3.28 %. At 500 ng/L, these effects intensified (yolk extension: 44.4 %; yolk sac area: -5.28 %). Body pigmentation decreased by 13.7 % compared to controls at 500 ng/L. At 5 ng/L, ROS levels and MDA content increased by 66.5 % and 53.4 %, respectively. Transcriptomic profiling at 16 h post-fertilization in embryos exposed to 500 ng/L DOCA identified significant gene expression changes concordant with phenotypic outcomes: (1) upregulation of six7, sox17, and cdx1a (associated with accelerated development); (2) downregulation of dct and slc45a2 (consistent with reduced pigmentation); (3) altered redox homeostasis, indicated by nox1 upregulation and hemoglobin gene downregulation; and (4) enhanced glycolytic/gluconeogenic activity, evidenced by upregulated pfkfb3, aldob, and pck2. These results demonstrate that the DOCA exposure perturbed embryonic zebrafish development, promoting accelerated morphogenesis concurrent with metabolic alterations and oxidative stress. This study provides the first evidence of DOCA's adverse effects on fish and advances understanding of understudied corticosteroids in ecotoxicology.