Disruption of endocrine function in in vitro H295R cell-based and in in vivo assay in zebrafish by 2,4-dichlorophenol

Yanbo MA, Jian HAN, Yongyong GUO, Paul K. S. LAM, Shiu Sun Rudolf WU, John P. GIESY, Xiaowei ZHANG, Bingsheng ZHOU

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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. Copyright © 2011 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)173-181
JournalAquatic Toxicology
Volume106-107
Early online date25 Nov 2011
DOIs
Publication statusPublished - 15 Jan 2012

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2,4-dichlorophenol
Zebrafish
Danio rerio
assays
gene
steroidogenesis
cells
Messenger RNA
Steroid 17-alpha-Hydroxylase
egg
chlorophenol
testosterone
steroid
Eggs
aquatic environment
hormone
cytochrome
hatching
Chlorophenols
Genes

Citation

Ma, Y., Han, J., Guo, Y., Lam, P. K. S., Wu, R. S. S., Giesy, J. P., . . . Zhou, B. (2012). Disruption of endocrine function in in vitro H295R cell-based and in in vivo assay in zebrafish by 2,4-dichlorophenol. Aquatic Toxicology, 106-107, 173-181. doi: 10.1016/j.aquatox.2011.11.006

Keywords

  • Hormones
  • In vitro
  • In vivo
  • H295R
  • HPG axis
  • Zebrafish