title: Chronic diclofenac exposure affects gill integrity and pituitary gene expression and displays estrogenic activity in nile tilapia (Oreochromis niloticus).
abstract: Oreochromis niloticus has been exposed to diclofenac (DCF), a nonsteroidal anti-inflammatory drug prevalent in the aquatic environment, for 80 days post-hatch (dph). Concentrations ranged from environmentally relevant (0.1 μg L-1and 1 μg L-1DCF) up to 100-fold thereof. Population relevant endpoints (hatching, survival, growth) as well as gill histopathology were analyzed. On this level of examination only gills exhibited mild to moderate alterations. On the contrary, biomarkers associated with reproduction were affected due to DCF exposure, indicating the potential to affect sexual differentiation and gametogenesis by acting as an estrogenic endocrine disrupting compound (EDC) in tilapia. Vitellogenin (VTG) gene expression was significantly induced at 1 μg L-1DCF. In order to find an explanation, gene expression patterns of key enzymes of the biotransformation phases I, II, and III have been analyzed. It seems very likely that the detoxification metabolism is induced in a dose dependent manner at higher concentrations of DCF leading to the expression pattern of VTG mRNA. Our results suggest that DCF at environmentally relevant concentrations adversely affects O. niloticus gill histopathology and pituitary gene expression, and has the potential to act as an estrogenic EDC. The sensitivity of various endpoints, however, differs and therefore these endpoints should be linked.
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: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D023681:Cichlids / Q000378:metabolism; D004008:Diclofenac / Q000737:chemistry / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000737:chemistry / Q000633:toxicity; D004970:Estrone / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D005880:Gills / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D014819:Vitellogenins / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D052244:Endocrine Disruptors; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004008:Diclofenac; D004970:Estrone
keywords: Fish; Gill histopathology; Gonadotropins; Low-dose exposure; Pharmaceutical; Vitellogenin