title: Diclofenac can exhibit estrogenic modes of action in male Xenopus laevis, and affects the hypothalamus-pituitary-gonad axis and mating vocalizations.
abstract: Diclofenac (DCF) is a non-steroidal analgesic and antiphlogistic. Due to its tremendous use, DCF can be found in the environment, especially in sewage, but also surface waters, ground and drinking water. Previous studies indicated that DCF can modulate the reproductive physiology of fish by altering the expression of important key enzymes of the hypothalamus-pituitary-gonad-axis (HPG-axis) and might act as an estrogenic endocrine disrupting chemical (EDC). Other studies, however, demonstrated that DCF does not exhibit any estrogenicity. Thus, in the present study we investigated whether an exposure to DCF can affect reproductive behavior and physiology of adult male X. laevis by analyzing DCF effects on the mate calling behavior of the frogs and on gene expression patterns of key biomarkers of the HPG-axis. In addition, plasma sex steroid levels were determined to gain detailed insights into the mechanisms of DCF action. We could demonstrate that DCF can act as EDC by exhibiting slight estrogenic modes of action. In addition, pharmacological impacts on gonadal steroidogenesis could be revealed leading to imbalances in sex steroid levels and ratios. DCF furthermore altered the calling behavior of exposed males, potentially reducing the mating and reproductive success of the frogs, possibly leading to severe population effects.
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany.
authors.forename: Norah Johanna
authors.initials: NJ
authors.lastname: Efosa
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, 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, Berlin, Germany; Department of Endocrinology, Institute of Biology, Humboldt-University Berlin, Berlin, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Kloas
authors.affiliation: Department of Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Berlin, Germany; Department Chemicals and Product Safety, Federal Institute for Risk Assessment, Berlin, Germany. Electronic address: Frauke.Hoffmann@bfr.bund.de.
authors.forename: Frauke
authors.initials: F
authors.lastname: Hoffmann
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology*; D004703:Endocrine System / Q000187:drug effects; D004970:Estrone / Q000378:metabolism*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006066:Gonads / Q000187:drug effects* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D014828:Vocalization, Animal / Q000187:drug effects*; D014982:Xenopus laevis / Q000502:physiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012739:Gonadal Steroid Hormones; D004008:Diclofenac; D004970:Estrone
keywords: Calling behavior; Diclofenac; Endocrine disruption; Estrogenicity; Hypothalamus-pituitary-gonad-axis