Hypoxia alters gene expression in the gonads of zebrafish (Danio rerio) ◊

The objectives of this study were to characterize gene expression responses to hypoxia in gonads of mature zebrafish (Danio rerio), and to start characterizing modes of action by which hypoxia could potentially alter reproduction. Adult male and female zebrafish were maintained under normoxia (7 mg O2/L), moderate hypoxia (3 mg O2/L), and severe hypoxia (1 mg O2/L) for 4 and 14 days and changes in gene expression in gonadal tissues (n = 5 per sex per treatment) were evaluated using a commercial 21,000 gene zebrafish oligonucleotide microarray. Differentially expressed genes were determined using ANOVA (p < 0.05), and enriched gene ontology (GO) categories (p < 0.01) identified using GeneSpring GX software. Short-term (4 d) exposure to hypoxia affected expression of genes associated with the initial adaptive responses such as: metabolism of carbohydrates and proteins, nucleotide metabolism, haemoglobin synthesis, reactive oxygen species metabolism, and locomotion. Prolonged (14 d) hypoxia affected a suite of genes belonging to different GO categories: lipid metabolism, reproduction (e.g., steroid hormone synthesis), and immune responses. Results of the present study demonstrate that reproduction likely would be affected by hypoxia via multiple modes of action. These include previously hypothesized mechanisms such as modulation of expression of steroidogenic genes, and downregulation of serotonergic pathway. In addition, we propose that there are multiple other points of disruption of reproductive system function linked, for example, to reorganization of lipid transport and other mechanisms involved in responding to hypoxia (e.g., hydroxysteroid dehydrogenase alterations, downregulation of contractile elements, etc.).