Baltic salmon (Salmo salar) yolk-sac fry mortality is associated with disturbances in the function of hypoxia-inducible transcription factor (HIF-1alpha) and consecutive gene expression

Aquat Toxicol. 2004 Jul 14;68(4):301-13. doi: 10.1016/j.aquatox.2004.03.019.


Baltic salmon (Salmo salar) suffer from abnormally high yolk-sac fry mortality designated as M74-syndrome. In 1990s, 25-80% of salmon females, which ascended rivers to spawn, produced yolk-sac fry suffering from the syndrome. Symptoms of M74-affected fry include neurological disturbances, impaired vascular development and abnormal haemorrhages. The latter symptoms are observed in mammalian embryos if the function of hypoxia inducible transcription factor (HIF-1alpha), its dimerization partner aryl hydrocarbon nuclear translocator (ARNT) or target gene vascular endothelial growth factor (VEGF) is disturbed. To study the possible involvement of HIF-1alpha and its target gene VEGF in the development of the syndrome, we collected healthy and M74-affected wild Baltic salmon yolk-sac fry and analyzed HIF-1alpha mRNA and protein expression, HIF-1alpha DNA-binding, target gene VEGF protein expression, and blood vessel density in both groups at different stages of yolk-sac fry development. In addition, since Baltic salmon females contain organochlorine contaminants, which have been suggested to be the cause of M74 syndrome via the aryl hydrocarbon receptor (AhR)-dependent gene expression pathway, we studied AhR protein expression, AhR DNA-binding and target gene CYP1A protein expression. Since the parents of both healthy and M74-affected wild fry will have experienced the organochlorine load from the Baltic Sea, hatchery-reared fry were included in the studies as an additional control. The results show that the vascular defects observed in fry suffering from M74 are associated with reduced DNA-binding activity of HIF-1alpha and subsequent downregulation of its target gene vascular endothelial growth factor (VEGF). In addition, also AhR function is decreased in diseased fry making it unlikely that symptoms of M74-affected fry would be caused by an upregulation of xenobiotically induced AhR-dependent gene expression pathway.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / metabolism
  • Abnormalities, Multiple / pathology
  • Abnormalities, Multiple / veterinary*
  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Blotting, Northern
  • Blotting, Western
  • DNA-Binding Proteins*
  • Electrophoretic Mobility Shift Assay
  • Female
  • Finland
  • Fish Diseases / metabolism*
  • Fish Diseases / mortality
  • Fish Diseases / pathology
  • Fresh Water
  • Gene Expression Regulation*
  • Histological Techniques
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Larva
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / pathology
  • Nervous System Diseases / veterinary*
  • RNA, Messenger / metabolism*
  • Receptors, Aryl Hydrocarbon / metabolism
  • Salmo salar
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism
  • Yolk Sac / metabolism
  • Yolk Sac / pathology*


  • DNA-Binding Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • Vascular Endothelial Growth Factor A
  • Aryl Hydrocarbon Receptor Nuclear Translocator