Hypoxia alters the expression of hif-1a mRNA and downstream HIF-1 response genes in embryonic and larval lake whitefish (Coregonus clupeaformis)

Lake whitefish (Coregonus clupeaformis) embryos and larvae were exposed to hypoxia at different developmental ages to determine when the cellular response to hypoxia could be initiated. mRNA levels of hypoxia-inducible factor la (hif-1 alpha), hsp70, and several HIF-1 target genes were quantified in embryos at 21, 38, 63, 83- and 103-days post fertilisation (dpf) and in larvae at 1, 2, 3- and 4-weeks post hatch (wph) following a 6-hour hypoxia exposure. hsp70 mRNA levels were increased in response to hypoxia at all embryonic ages. By comparison, the first observed change in hif-1 alpha mRNA in response to hypoxia was at 38 dpf, where it was down-regulated from high basal levels, with this response persisting through to 83 dpf. Interestingly, this decrease in hif-1 alpha mRNA coincided with increases in the mRNA levels of the HIF-1 target genes: vegfa (vascular endothelial growth factor A), igfbp1 (insulin-like growth factor binding protein 1), ldha (lactate dehydrogenase a), gopdh (glyceraldehyde-3-phosphate dehydrogenase) and epo (erythropoietin) at select ages. Collectively, this suggests a possible HIF-1-mediated response to hypoxia despite a decrease in hif-1 alpha mRNA. Coinciding with a decrease in basal levels, increases in hif-1 alpha were measured in response to hypoxia at 103 dpf and in larval fish at 1, 2 and 3 wph but there were no consistent increases in HIF-1 target genes at these ages. Overall, our findings indicate that lake whitefish can mount a response to hypoxia early in embryogenesis which may mitigate some of the damaging effects of exposure to low oxygen levels at these critical life history stages.