Estrogenic effects associated with bisphenol a exposure in male zebrafish (Danio rerio) is associated with changes.of endogenous 17β-estradiol and gene specific DNA methylation levels

The binding affinity of bisphenol A (BPA) to estrogen receptors (ERs) is much lower than that of 17 beta-estradiol (E-2), and whether there are other molecular mechanisms responsible for the estrogenic action of BPA in vivo currently remains unknown. The objective of this study was to explore the potential association between the estrogenic effect induced by bisphenol A in vivo and changes of endogenous E-2 and gene specific DNA methylation levels. After a waterborne exposure of male zebrafish to 500, 1000, or 1500 mu g/L of BPA for 21 d, vitellogenin (VTG) concentration in whole body homogenate, plasma E-2 and testosterone levels, hepatic ERs mRNA expressions, gonadal cyp19al a and cypl7a1 mRNA expressions, and methylation levels of hepatic esri and gonadal cypl9ala's promoters were determined. Our results indicated that for the 500 and 1500 mu g/L. treatment groups, VTG might be induced mainly by the elevated E-2 levels; increases of E-2 levels could be partly explained by the up-regulated expression of gonadal aromatase, mRNA levels of which were found to be negatively related to the methylation levels of both its promoter and one CpG site. In addition, upon BPA exposure, hepatic esrl mRNA levels were also negatively related to the methylation levels of both its promoter and one CpG site. These observations provide evidence for the non-ERs mediated mechanisms underlying the estrogenic action of BPA on male zebrafish. (C) 2017 Elsevier Inc. All rights reserved.