TY - JOUR
T1 - Disruption of endocrine function in in vitro H295R cell-based and in in vivo assay in zebrafish by 2,4-dichlorophenol
AU - Ma, Yanbo
AU - Han, Jian
AU - Guo, Yongyong
AU - Lam, Paul K.S.
AU - Wu, Rudolf S.S.
AU - Giesy, John P.
AU - Zhang, Xiaowei
AU - Zhou, Bingsheng
N1 - Funding Information:
This work was supported by Chinese Academy of Sciences ( KZCX2-YW-Q02-05 ), the National Nature Science Foundation of China (no. 20890113 ), and t he State Key Laboratory of Freshwater Ecology and Biotechnology ( 2008FBZ10 ). The research was supported, in part, by a Discovery Grant from the National Science and Engineering Research Council of Canada (Project # 326415-07) and a grant from the Western Economic Diversification Canada (Project # 6578 and 6807). Prof. Giesy was supported by the Canada Research Chair program, an at large Chair Professorship at the Department of Biology and Chemistry and State Key Laboratory in Marine Pollution, City University of Hong Kong, The Einstein Professor Program of the Chinese Academy of Sciences and the Visiting Professor Program of King Saud University. The authors also wish to thank the two anonymous reviewers for their constructive comments.
PY - 2012/1/15
Y1 - 2012/1/15
N2 - 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.
AB - 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.
KW - H295R
KW - HPG axis
KW - Hormones
KW - In vitro
KW - In vivo
KW - Zebrafish
UR - http://www.scopus.com/inward/record.url?scp=82955189216&partnerID=8YFLogxK
U2 - 10.1016/j.aquatox.2011.11.006
DO - 10.1016/j.aquatox.2011.11.006
M3 - Article
C2 - 22155427
AN - SCOPUS:82955189216
SN - 0166-445X
VL - 106-107
SP - 173
EP - 181
JO - Aquatic Toxicology
JF - Aquatic Toxicology
ER -