title: Disruption of endocrine function in in vitro H295R cell-based and in in vivo assay in zebrafish by 2,4-dichlorophenol.
abstract: Chlorophenols in the aquatic environment have been of concern due to their potential effects on human and wildlife. In the present study, the endocrine disrupting effects of 2,4-dichlorophenol (2,4-DCP) were investigated in vitro and in vivo. In the in vitro assay, H295R human adrenocortical carcinoma cells were used to determine the potential effects of 2,4-DCP on steroidogenesis. Exposure to 0, 0.1, 0.3 or 1.0 mg 2,4-DCP/L resulted in less production of 17β-estradiol (E2) and alterations in transcript expressions of genes involved in steroidogenesis, including cytochrome P450 (CYP11A, CYP17, CYP19), 3βHSD, 17βHSD and StAR. In the in vivo study, effects of 0, 0.03, 0.1 or 0.3 mg 2,4-DCP/L on concentrations of steroid hormones in plasma of adult zebrafish (Danio rerio) were measured and expression of mRNA of selected genes in hypothalamic-pituitary-gonadal (HPG) axis and liver were determined. Exposure of zebrafish to 2,4-DCP resulted in lesser concentrations of E2 accompanied by down-regulation of CYP19A mRNA in the females. In males, exposure to 2,4-DCP resulted in greater concentrations of testosterone (T) and E2 along with greater mRNA expression of CYP17 and CYP19A. The mRNA expression of prostaglandin synthase (Ptgs2) gene, which regulates ovulation, was down-regulated in females, but up-regulated in males. The hepatic estrogenic receptor (ERα and ERβ) and vitellogenin (VTG1 and VTG3) mRNAs were up-regulated in both females and males. The average number of eggs spawned was significantly less upon exposure to 2,4-DCP. Exposure of adult zebrafish to 2,4-DCP resulted in lesser rates of hatching of eggs. The results demonstrated that 2,4-DCP modulates transcription of steroidogenetic genes in both H295R cells and in the zebrafish HPG-axis and disrupts steroidogenesis, which in turn, can cause adverse effects on reproduction in fish.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Ma
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Guo
authors.forename: Paul K S
authors.initials: PK
authors.lastname: Lam
authors.forename: Rudolf S S
authors.initials: RS
authors.lastname: Wu
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Bingsheng
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D002733:Chlorophenols / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D013739:Testosterone / Q000235:genetics / Q000378:metabolism; D014819:Vitellogenins / Q000235:genetics / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D000871:Anthelmintics; D015415:Biomarkers; D002733:Chlorophenols; D052244:Endocrine Disruptors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; C004762:2,4-dichlorophenol