Data from: Hypoxia-inducible factor-1 mediates adaptive developmental plasticity of hypoxia tolerance in zebrafish, Danio rerio

In recent years, natural and anthropogenic factors have increased aquatic hypoxia the world over. In most organisms, the cellular response to hypoxia is mediated by the master regulator hypoxia-inducible factor-1 (HIF-1). HIF-1 also plays a critical role in the normal development of the cardiovascular system of vertebrates. We tested the hypothesis that hypoxia exposures which resulted in HIF-1 induction during embryogenesis would be associated with enhanced hypoxia tolerance in subsequent developmental stages. We exposed zebrafish (Danio rerio) embryos to just 4 h of severe hypoxia or total anoxia at 18, 24 and 36 h post-fertilization (hpf). Of these, exposure to hypoxia at 24 and 36 hpf as well as anoxia at 36 hpf activated the HIF-1 cellular pathway. Zebrafish embryos that acutely upregulated the HIF-1 pathway had an increased hypoxia tolerance as larvae. The critical window for hypoxia sensitivity and HIF-1 signalling was 24 hpf. Adult male fish had a lower critical oxygen tension (Pcrit) compared with females. Early induction of HIF-1 correlated directly with an increased proportion of males in the population. We conclude that mounting a HIF-1 response during embryogenesis is associated with long-term impacts on the phenotype of later stages which could influence both individual hypoxia tolerance and population dynamics.

近年来，自然与人为因素已在全球范围内加剧了水体低氧现象。在绝大多数生物体内，低氧的细胞应答由核心调控因子低氧诱导因子-1（hypoxia-inducible factor-1, HIF-1）介导。HIF-1同时在脊椎动物心血管系统的正常发育过程中发挥关键作用。本研究验证了如下假说：胚胎发育阶段暴露于低氧并诱导HIF-1表达，将与后续发育阶段的低氧耐受能力提升存在关联。我们分别在受精后18、24及36小时（hours post-fertilization, hpf）对斑马鱼（Danio rerio）胚胎进行时长仅4小时的重度低氧或完全无氧暴露。其中，在24和36 hpf时进行低氧暴露，以及在36 hpf时进行无氧暴露，均可激活HIF-1细胞通路。急性上调HIF-1通路的斑马鱼胚胎，在幼体阶段表现出更高的低氧耐受能力。低氧敏感性与HIF-1信号通路的关键时间窗口为24 hpf。成年雄性斑马鱼的临界氧张力（critical oxygen tension, Pcrit）低于雌性个体。胚胎早期的HIF-1诱导与种群中雄性比例的升高直接相关。本研究得出结论：胚胎发育阶段启动HIF-1应答，会对后续发育阶段的表型产生长期影响，该影响既可能作用于个体的低氧耐受能力，也可对种群动态产生调控作用。