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.
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.
Vuori
Kristiina A M
KA
Laboratory of Animal Physiology, Department of Biology, University of Turku, FI-20014 Turku, Finland.
Soitamo
Arto
A
Vuorinen
Pekka J
PJ
Nikinmaa
Mikko
M
D000015:Abnormalities, Multiple / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D015152:Blotting, Northern; D015153:Blotting, Western; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005387:Finland; D005393:Fish Diseases / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005618:Fresh Water; D005786:Gene Expression Regulation; D006652:Histological Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007814:Larva; D009422:Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D012333:RNA, Messenger / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020317:Salmo salar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D015017:Yolk Sac / Q000378:metabolism / Q000473:pathology*
D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator