Carotenoid glycosides from cyanobacteria are teratogenic in the zebrafish (Danio rerio) embryo model

•Myxol glycosides from cyanobacteria were identified as teratogenic in the zebrafish embryo model.•Comparison to other carotenoids and retinoids shows congener-specific teratogenicity.•A model of teratogenicity of carotenoids as pro-retinoids is proposed.•Relevance of teratogenicity to declines in aquatic vertebrates is discussed.

Toxigenicity of cyanobacteria is widely associated with production of several well-described toxins that pose recognized threats to human and ecosystem health as part of both freshwater eutrophication, and episodic blooms in freshwater and coastal habitats. However, a preponderance of evidence indicates contribution of additional bioactive, and potentially toxic, metabolites. In the present study, the zebrafish (Danio rerio) embryo was used as a model of vertebrate development to identify, and subsequently isolate and characterize, teratogenic metabolites from two representative strains of C. raciborskii. Using this approach, three chemically related carotenoids - and specifically the xanthophyll glycosides, myxol 2′-glycoside (1), 4-ketomyxol 2′-glycoside (2) and 4-hydroxymyxol 2′-glycoside (3) - which are, otherwise, well known pigment molecules from cyanobacteria were isolated as potently teratogenic compounds. Carotenoids are recognized “pro-retinoids” with retinoic acid, as a metabolic product of the oxidative cleavage of carotenoids, established as both key mediator of embryo development and, consequently, a potent teratogen. Accordingly, a comparative toxicological study of chemically diverse carotenoids, as well as apocarotenoids and retinoids, was undertaken. Based on this, a working model of the developmental toxicity of carotenoids as pro-retinoids is proposed, and the teratogenicity of these widespread metabolites is discussed in relation to possible impacts on aquatic vertebrate populations.

Graphical abstractDownload high-res image (59KB)Download full-size image