title: Retinoid-like activity and teratogenic effects of cyanobacterial exudates.
abstract: Retinoic acids and their derivatives have been recently identified by chemical analyses in cyanobacteria and algae. Given the essential role of retinoids for vertebrate development this has raised concerns about a potential risk for vertebrates exposed to retinoids during cyanobacterial blooms. Our study focuses on extracellular compounds produced by phytoplankton cells (exudates). In order to address the capacity for the production of retinoids or compounds with retinoid-like activity we compared the exudates of ten cyanobacteria and algae using in vitro reporter gene assay. Exudates of three cyanobacterial species showed retinoid-like activity in the range of 269-2,265 ng retinoid equivalents (REQ)/L, while there was no detectable activity in exudates of the investigated algal species. The exudates of one green alga (Desmodesmus quadricaudus) and the two cyanobacterial species with greatest REQ levels, Microcystis aeruginosa and Cylindrospermopsis raciborskii, were selected for testing of the potential relation of retinoid-like activity to developmental toxicity in zebrafish embryos. The exudates of both cyanobacteria were indeed provoking diverse teratogenic effects (e.g. tail, spine and mouth deformation) and interference with growth in zebrafish embryos, while such effects were not observed for the alga. Fish embryos were also exposed to all-trans retinoic acid (ATRA) in a range equivalent to the REQ concentrations detected in exudates by in vitro bioassays. Both the phenotypes and effective concentrations of exudates corresponded to ATRA equivalents, supporting the hypothesis that the teratogenic effects of cyanobacterial exudates are likely to be associated with retinoid-like activity. The study documents that some cyanobacteria are able to produce and release retinoid-like compounds into the environment at concentrations equivalent to those causing teratogenicity in zebrafish. Hence, the characterization of retinoid-like and teratogenic potency should be included in the assessment of the potential adverse effects caused by the release of toxic and bioactive compounds during cyanobacterial blooms.
authors.affiliation: RECETOX-Masaryk University, Faculty of Science, Brno, Czech Republic.
authors.forename: Adam
authors.initials: A
authors.lastname: Jonas
authors.affiliation: RECETOX-Masaryk University, Faculty of Science, Brno, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Buranova
authors.affiliation: UFZ-Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scholz
authors.affiliation: UFZ-Helmholtz Centre for Environmental Research, Department of Bioanalytical Ecotoxicology, Leipzig, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Fetter
authors.affiliation: RECETOX-Masaryk University, Faculty of Science, Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Novakova
authors.affiliation: RECETOX-Masaryk University, Faculty of Science, Brno, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kohoutek
authors.affiliation: RECETOX-Masaryk University, Faculty of Science, Brno, Czech Republic. Electronic address: hilscherova@recetox.muni.cz.
authors.forename: Klara
authors.initials: K
authors.lastname: Hilscherova
mesh_terms: D000818:Animals; D001681:Biological Assay; D000460:Chlorophyta / Q000378:metabolism*; D046891:Cylindrospermopsis / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D046931:Microcystis / Q000378:metabolism*; D012176:Retinoids / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D013723:Teratogens; D014212:Tretinoin / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015027:Zebrafish / Q000196:embryology
chemical_list: D012176:Retinoids; D013723:Teratogens; D014874:Water Pollutants, Chemical; D014212:Tretinoin
keywords: All-trans retinoic acid; Cyanobacteria; Developmental toxicity; Retinoids; Zebrafish embryo