Aquatic surface respiration improves survival during hypoxia in zebrafish ( Danio rerio ) lacking hypoxia-inducible factor 1-α

• Published in: Proceedings of the Royal Society. B, Biological sciences Vol. 289; no. 1966; p. 20211863
• Main Authors: Mandic, Milica, Flear, Kaitlyn, Qiu, Pearl, Pan, Yihang K, Perry, Steve F, Gilmour, Kathleen M
• Format: Journal Article
• Language: English
• Published: England The Royal Society 12.01.2022
• Subjects: Animals; Development and Physiology; Gene Expression Regulation; Hypoxia; Larva - physiology; Respiration; Zebrafish - physiology; aquatic surface respiration; early development; hypoxia-inducible factor-1α; zebrafish; intermittent hypoxia; survival
• ISSN: 0962-8452; 1471-2954
• DOI: 10.1098/rspb.2021.1863

Hypoxia-inducible factor 1-α (Hif-1α), an important transcription factor regulating cellular responses to reductions in O , previously was shown to improve hypoxia tolerance in zebrafish ( ). Here, we examined the contribution of Hif-1α to hypoxic survival, focusing on the benefit of aquatic surface respiration (ASR). Wild-type and Hif-1α knockout lines of adult zebrafish were exposed to two levels (moderate or severe) of intermittent hypoxia. Survival was significantly compromised in Hif-1α knockout zebrafish prevented from accessing the surface during severe (16 mmHg) but not moderate (23 mmHg) hypoxia. When allowed access to the surface in severe hypoxia, survival times did not differ between wild-type and Hif-1α knockouts. Performing ASR mitigated the negative effects of the loss of Hif-1α with the knockouts initiating ASR at a higher O threshold and performing ASR for longer than wild-types. The loss of Hif-1α had little impact on survival in fish between 1 and 5 days post-fertilization, but as the larvae aged, their reliance on Hif-1α increased. Similar to adult fish, ASR compensated for the loss of Hif-1α on survival. Together, these results demonstrate that age, hypoxia severity and, in particular, the ability to perform ASR significantly modulate the impact of Hif-1α on survival in hypoxic zebrafish.