title: The effects of the urea-based herbicide linuron on reproductive endpoints in the fathead minnow (Pimephales promelas).
abstract: Linuron is a widely used urea-based herbicide that has anti-androgenic activity in both fish and rodents. To further elucidate the potential mode of action (MOA) of linuron on the vertebrate endocrine system, adult male and female fathead minnows were exposed for 21 days to dechlorinated water, a solvent control, 17β-estradiol (E2; 0.1 μg/L), dihydrotestosterone (DHT; 100 μg/L), linuron (1, 10, 100 μg/L) and one co-treatment of DHT (100 μg/L) and linuron (100 μg/L). There were no effects of linuron on egg hatching, 7 day egg survival, nuptial tubercle formation or gonadal histopathology. Administration of DHT and 1 and 100 μg/L linuron reduced plasma vitellogenin in females, while male plasma vitellogenin were induced after E2 exposure and co-exposure of DHT and linuron. Ovarian mRNA levels were examined for several genes involved in steroidogenesis (e.g. p450scc, cyp19a, star, tspo, hsd17b and hsd11b) and estrogen-mediated responses (esr1, esr2b, esr2a). Only p450scc mRNA was significantly decreased with DHT+linuron co-treatment. Clustering of steroidogenic mRNA transcript expression patterns revealed that patterns for linuron were more similar to E2 compared to DHT. Collectively, this study supports the hypothesis that linuron may not be a pure anti-androgen and may have multiple MOAs that affect vertebrate reproduction.
authors.affiliation: Nautilus Environmental, Imperial Square Lake City, Burnaby, British Columbia, Canada. vicki.marlatt@ufv.ca
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Marlatt
authors.forename: Bonnie P
authors.initials: BP
authors.lastname: Lo
authors.forename: Anna
authors.initials: A
authors.lastname: Ornostay
authors.forename: Natacha S
authors.initials: NS
authors.lastname: Hogan
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Kennedy
authors.forename: James R
authors.initials: JR
authors.lastname: Elphick
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000818:Animals; D016000:Cluster Analysis; D003530:Cyprinidae / Q000235:genetics / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling; D006066:Gonads / Q000187:drug effects / Q000254:growth & development; D006540:Herbicides / Q000494:pharmacology; D008044:Linuron / Q000494:pharmacology*; D008297:Male; D010053:Ovary / Q000187:drug effects / Q000378:metabolism; D010063:Ovum / Q000187:drug effects / Q000254:growth & development; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014508:Urea / Q000494:pharmacology; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
chemical_list: D000728:Androgens; D004967:Estrogens; D006540:Herbicides; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D008044:Linuron; D013196:Dihydrotestosterone; D004958:Estradiol; D014508:Urea