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

Author:
Hou, Jie, Su, Yujing, Lin, Wang, Guo, Honghui, Li, Li, Anderson, Donald M., Li, Dapeng, Tang, Rong, Chi, Wei, Zhang, Xi
Source:
Environmental pollution 2018 v.240 pp. 615-622
ISSN:
0269-7491
Subject:
Danio rerio, adults, estradiol, estrogenic properties, gene expression regulation, genes, liver, males, microcystin-LR, protein content, reproductive performance, risk, steroidogenesis, testes, testosterone, toxicity, transcription (genetics), wildlife
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.
Agid:
5973256