The effects of short-term hypoxia on hypoxia-inducible factor 1 alpha mRNA and microRNA in Fundulus heteroclitus

Hypoxia-inducible factor 1 (Hif1) is responsible for coordinating and regulating much of the response to acute hypoxia in vertebrates. This complex response is multifactorial, involving a large network of regulators. Within this network, epigenetic modulators, such as microRNA (miRNA), have garnered increasing interest due to their ability to regulate and fine-tune a myriad of cellular processes. Thus, we aimed to determine the effects of acute mild hypoxia on four known hypoxia-responsive miRNAs, along with three hypoxia-related transcripts. To do this, we exposed Atlantic killifish, Fundulus heteroclitus, to either normoxic (∼ 8.70 mg O₂ l^-1) or mild hypoxic (∼ 2.40 mg O₂ l^-1) conditions and sampled the gills and brain tissue throughout the exposure (0, 1, 3, 6, 12 h). While mild hypoxia resulted in a downregulation of gill hif1α mRNA, one of its downstream targets, insulin-like growth factor-binding protein 1 (igfbp1), was significantly upregulated. Furthermore, hif1α mRNA, along with several miRNAs (miR-18, miR-455-3p, and miR-222), varied across time, suggesting potential involvement of the circadian clock. Finally, we observed that mild hypoxia resulted in differential expression of miR-210-5p and miR-222 in the brain, but not the gills, indicating tissue-specific epigenetic differences. Collectively, our results emphasize the complexity of the Hif1-mediated hypoxic response, warranting further investigation into underlying epigenetic mechanisms.