Data from: HIF-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 acute induction of HIF-1 during embryogenesis would correspond with an enhanced hypoxia tolerance in subsequent developmental stages. We exposed zebrafish (Danio rerio) embryos to just 4h of severe hypoxia or total anoxia at 18, 24 and 36 hours 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 up-regulated 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 to 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，自然与人为因素在全球范围内加剧了水体低氧现象。在绝大多数生物中，机体对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调控作用。我们提出假说：胚胎发育阶段急性诱导HIF-1表达，将能提升后续发育阶段的低氧耐受能力。我们将斑马鱼（Danio rerio）胚胎分别在受精后18、24及36小时（hours post fertilization, hpf）暴露于严重低氧或完全缺氧环境中，暴露时长仅为4小时。其中，在24 hpf和36 hpf时进行低氧暴露，以及在36 hpf时进行完全缺氧暴露，均可激活HIF-1细胞信号通路。急性上调HIF-1通路的斑马鱼胚胎，在发育为幼体时展现出更强的低氧耐受能力。低氧敏感性与HIF-1信号通路调控的关键时间窗口为24 hpf。成年雄性斑马鱼的临界氧分压（critical oxygen tension, Pcrit）低于雌性个体。胚胎早期HIF-1的诱导表达与种群中雄性个体比例的升高呈直接正相关。综上，我们认为胚胎发育阶段启动HIF-1应答，会对后续发育阶段的表型产生长期影响，该影响可同时作用于个体低氧耐受能力与种群动态调控。