Enhanced GSH synthesis by Bisphenol A exposure promoted DNA methylation process in the testes of adult rare minnow Gobiocypris rarus

Abstract

DNA methylation is a commonly studied epigenetic modification. The mechanism of BPA on DNA methylation is poorly understood. The present study aims to explore whether GSH synthesis affects DNA methylation in the testes of adult male rare minnow Gobiocypris rarus in response to Bisphenol A (BPA). Male G. rarus was exposed to 1, 15 and 225μgL⿿1 BPA for 7 days. The levels of global DNA methylation, hydrogen peroxide (H2O2) and glutathione (GSH) in the testes were analyzed. Meanwhile, the levels of enzymes involved in DNA methylation and de novo GSH synthesis, and the substrate contents for GSH production were measured. Furthermore, gene expression profiles of the corresponding genes of all studied enzymes were analyzed. Results indicated that BPA at 15 and 225μgL⿿1 caused hypermethylation of global DNA in the testes. The 15μgL⿿1 BPA resulted in significant decrease of ten-eleven translocation proteins (TETs) while 225μgL⿿1 BPA caused significant increase of DNA methyltransferase proteins (DNMTs). Moreover, 225μgL⿿1 BPA caused significant increase of H2O2 and GSH levels, and the de novo GSH synthesis was enhanced. These results indicated that the significant decrease of the level of TETs may be sufficient to cause the DNA hypermethylation by 15μgL⿿1 BPA. However, the significantly increased of DNMTs contributed to the significant increase of DNA methylation levels by 225μgL⿿1 BPA. Moreover, the elevated de novo GSH synthesis may promote the DNA methylation process.