PUBLICATION

Estrogenic potency of MC-LR is induced via stimulating steroidogenesis: In vitro and in vivo evidence

Authors
Hou, J., Su, Y., Lin, W., Guo, H., Li, L., Anderson, D.M., Li, D., Tang, R., Chi, W., Zhang, X.
ID
ZDB-PUB-180518-8
Date
2018
Source
Environmental pollution (Barking, Essex : 1987)   240: 615-622 (Journal)
Registered Authors
Keywords
Endocrine disruption, Estrogenic effect, H295R cell, Microcystins, Zebrafish
MeSH Terms
  • Animals
  • Aromatase/biosynthesis
  • Cell Line
  • Estradiol/metabolism
  • Estrogens/toxicity*
  • Estrone/metabolism
  • Gonadal Steroid Hormones/metabolism*
  • Humans
  • Liver/metabolism
  • Male
  • Microcystins/toxicity*
  • Receptors, Estrogen/metabolism
  • Reproduction/drug effects*
  • Testis/drug effects
  • Testosterone/metabolism
  • Up-Regulation/drug effects
  • Water Pollutants, Chemical/toxicity*
  • Zebrafish/metabolism
  • Zebrafish Proteins/biosynthesis
PubMed
29772511 Full text @ Environ. Pollut.
Abstract
Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes. In the in vivo assay, adult male zebrafish were exposed to 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d. Similarly, E2 and T contents in the testis were increased, accompanied by extensive up-regulation of steroidogenic genes, especially cyp19a. Meanwhile, the percentage of spermatid in the testis declined. In the liver, the vtg1 gene was significantly up-regulated while both the transcriptional and protein levels of the estrogenic receptor (ER) declined. These results indicate that MC-LR induced non-dose-dependent estrogenic effects at environmental concentrations, which may result from steroidogenesis stimulation via a non-ER-mediated pathway. Our findings support a paradigm shift in the risk assessment of MC-LR from traditional toxicity to estrogenic risk, particularly at low concentrations, and emphasize the potential threat to the male reproductive capacity of wildlife in bloom areas.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping