title: Chronic Exposure of Marine Medaka (Oryzias melastigma) to 4,5-Dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) Reveals Its Mechanism of Action in Endocrine Disruption via the Hypothalamus-Pituitary-Gonadal-Liver (HPGL) Axis.
abstract: In this study, marine medaka (Oryzias melastigma) were chronically exposed for 28 days to environmentally realistic concentrations of 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT) (0, 0.76, 2.45, and 9.86 μg/L), the active ingredient in commercial antifouling agent SeaNine 211. Alterations of the hypothalamus-pituitary-gonadal-liver (HPGL) axis were investigated across diverse levels of biological organization to reveal the underlying mechanisms of its endocrine disruptive effects. Gene transcription analysis showed that DCOIT had positive regulatory effects mainly in male HPGL axis with lesser extent in females. The stimulated steroidogenic activities resulted in increased concentrations of steroid hormones, including estradiol (E2), testosterone (T), and 11-KT-testosterone (11-KT), in the plasma of both sexes, leading to an imbalance in hormone homeostasis and increased E2/T ratio. The relatively estrogenic intracellular environment in both sexes induced the hepatic synthesis and increased the liver and plasma content of vitellogenin (VTG) or choriogenin. Furthermore, parental exposure to DCOIT transgenerationally impaired the viability of offspring, as supported by a decrease in hatching and swimming activity. Overall, the present results elucidated the estrogenic mechanisms along HPGL axis for the endocrine disruptive effects of DCOIT. The reproductive impairments of DCOIT at environmentally realistic concentrations highlights the need for more comprehensive investigations of its potential ecological risks.
authors.affiliation: HKUST Shenzhen Research Institute and Division of Life Science, Hong Kong University of Science and Technology , Clear Water Bay, Hong Kong SAR, China.
authors.forename: Lianguo
authors.initials: L
authors.lastname: Chen
authors.affiliation: HKUST Shenzhen Research Institute and Division of Life Science, Hong Kong University of Science and Technology , Clear Water Bay, Hong Kong SAR, China.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Ye
authors.forename: Chenyan
authors.initials: C
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
authors.forename: Qiangwei
authors.initials: Q
authors.lastname: Wang
authors.forename: Frauke
authors.initials: F
authors.lastname: Seemann
authors.forename: Doris W T
authors.initials: DW
authors.lastname: Au
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Wuhan 430072, China.
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Toxicology Centre, University of Saskatchewan , 44 Campus Drive, Saskatoon, SK S7N 5B3, Canada.
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.affiliation: HKUST Shenzhen Research Institute and Division of Life Science, Hong Kong University of Science and Technology , Clear Water Bay, Hong Kong SAR, China.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
mesh_terms: D000818:Animals; D052244:Endocrine Disruptors / Q000378:metabolism / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D005260:Female; D006066:Gonads / Q000187:drug effects*; D007031:Hypothalamus / Q000187:drug effects*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009990:Oryzias / Q000097:blood / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects*; D012098:Reproduction / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D013844:Thiazoles / Q000378:metabolism / Q000633:toxicity*; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D052244:Endocrine Disruptors; D013844:Thiazoles; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D013739:Testosterone; D004958:Estradiol; C080469:Kathon 930