title: Chronic exposure to the ß-blocker metoprolol reduces growth and alters gene expression of gonadotropins and vitellogenin in Nile tilapia (Oreochromis niloticus).
abstract: Knowledge of the occurrence and impacts of human pharmaceuticals in the aquatic environment is increasing since many years. Ecotoxicological studies mainly focus on acute effects though; chronic exposure studies are still rare. ß-adrenergic receptor antagonists (ß-blockers) are widely detected in the aquatic environment and likely alter the physiology of aquatic vertebrates due to a well-conserved adrenergic system. In this study, Nile tilapia (Oreochromis niloticus) were exposed to four different concentrations (4×10-10M, 4×10-9M, 4×10-8M and 4×10-7M) of metoprolol (ß1-blocker) from fertilized egg until 80 days post-hatch. Hatching and survival were not affected but growth was reduced almost dose-dependently after 30 and 80 days post-hatch. Histopathological evaluation of the gills revealed the tendency of mild alterations with proliferation of mucous/chloride cells and infiltration by leucocytes as the main findings. The transcriptional responses of both pituitary gonadotropins (luteinizing hormone and follicle stimulating hormone) as well as the estrogenic biomarker vitellogenin indicated moderately altered endocrine processes due to metoprolol exposure at the concentrations chosen. In contrast, hepatic detoxification mechanisms displayed only little to no effects. Based on this study, the overall toxicity of metoprolol in fish at environmentally relevant concentrations seems to be rather low.
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany. Electronic address: frederike.groener@igb-berlin.de.
authors.forename: Frederike
authors.initials: F
authors.lastname: Gröner
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Höhne
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Kleiner
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Müggelseedamm 301, 12587 Berlin, Germany; Department of Endocrinology, Institute of Biology, Humboldt University, Invalidenstr. 42, 10099 Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kloas
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000633:toxicity*; D000818:Animals; D023681:Cichlids / Q000235:genetics / Q000254:growth & development*; D004305:Dose-Response Relationship, Drug; D004970:Estrone / Q000235:genetics / Q000378:metabolism; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005880:Gills / Q000187:drug effects / Q000254:growth & development; D006062:Gonadotropins / Q000235:genetics* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000235:genetics / Q000378:metabolism; D008790:Metoprolol / Q000633:toxicity*; D014819:Vitellogenins / Q000235:genetics* / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000319:Adrenergic beta-Antagonists; D006062:Gonadotropins; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004970:Estrone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D008790:Metoprolol
keywords: Detoxification; Environmentally relevant concentrations; Estrogenic biomarker; Fish; Gill histopathology; Pharmaceutical