Does hypoxia-inducible factor 1α play a role in regulating cutaneous oxygen flux in larval zebrafish (Danio rerio)?

Previous studies have demonstrated that hypoxia tolerance is improved in zebrafish (Danio rerio) larvae after prior exposure to lowered ambient O levels. Such improved hypoxia performance was attributed in part, to increased levels of hypoxia-inducible factor 1α (Hif-1α) exerting downstream effects on various physiological processes including promotion of trunk skin angiogenesis. Since O uptake ([Formula: see text]) in larvae is facilitated largely by O diffusion across the skin, enhanced cutaneous vascularization is expected to enhance [Formula: see text] during hypoxia and thus contribute to improved hypoxia tolerance. In this study, we used the scanning micro-optrode technique together with quantification of cutaneous vascularity in wild types (WT) and Hif-1α knockouts (hif1aaab) to test the hypothesis that improved hypoxia tolerance after hypoxia acclimation in larvae at 4 or 7 days post-fertilization (dpf) was associated with Hif-1α-dependent increases in skin vascularity and regional cutaneous O fluxes (JO). Hypoxia tolerance, as determined by measurements of critical PO (P), was unaltered by hypoxia pre-exposure in larvae at 4 dpf and there were no significant differences in P between WT and hif1aaab larvae at this developmental stage. However, at 7 dpf there was a significant effect of genotype with WT larvae showing a lower P than hif1aaab larvae, an effect that was being driven by a reduced P in the WT larvae after hypoxia pre-exposure (19.2 ± 1.9 mmHg) compared to hif1aaab fish (35.5 ± 3.5 mmHg). Regardless of genotype, pre-exposure status or developmental age, JO decreased along the body in the anterior-to-posterior direction. Neither hypoxia pre-exposure nor genotype affected JO at any region along the body. The lack of any effect of hypoxia pre-exposure or genotype on JO was consistent with the lack of any effect on skin vascularity as measured in Tg(fli1:EGFP) transgenic larvae. Thus, the decreased hypoxia performance (increased P) at 7 dpf in the hif1aaab larvae did not appear to be reliant on changes in trunk vascularity or cutaneous O diffusion.