DNA demethylation mediated by down-regulated TETs in the testes of rare minnow Gobiocypris rarus under bisphenol A exposure

Inevitable BPA exposure resulted in disturbance of DNA methylation status and our published study suspected that BPA has the potentiality to disturb DNA demethylation and GSH production in Gobiocypris rarus testes. To confirm this conjecture, several experiments were carried out in the present study. Adult male G. rarus was exposed to 1, 15 and 225 mu g L-1 (nominal concentration) BPA for two weeks. The levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), glutathione (GSH), and enzyme levels for DNA methylation and GSH synthesis in the testes were detected. Meanwhile, the contents of substrates for GSH synthesis were measured. Furthermore, the transcriptional changes of the studied genes were examined. Results indicated that 1-225 mu g L-1 BPA caused decrease of testicular ten-eleven translocation proteins (TETs) with more obvious effects at low concentrations. Moreover, all concentrations of BPA resulted in decrease of 5hmC levels while only 225 mu g L-1 BPA resulted in significant increase of 5mC. In addition, all treatments resulted in significant decrease of GSH and the replenishment of GSH might be mainly accomplished by circular synthesis. These results indicated that BPA exposure inhibited TET-smediated DNA demethylation and the declined DNA demethylation mediated by TETs may result in DNA hypermethylation at 225 mu g L-1 BPA. In addition, the changes of DNA methylation status were irrelevant with GSH levels. (C) 2016 Elsevier Ltd. All rights reserved.