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

Hou, Jie, Su, Yujing, Lin, Wang, Guo, Honghui, Li, Li, Anderson, Donald M., Li, Dapeng, Tang, Rong, Chi, Wei, Zhang, Xi
Environmental pollution 2018 v.240 pp. 615-622
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
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.