Global genomic methylation levels in the liver and gonads of the three-spine stickleback (Gasterosteus aculeatus) after exposure to hexabromocyclododecane and 17-β oestradiol

Abstract

Alteration of DNA methylation is a major epigenetic mechanism associated with the effects of nongenotoxic carcinogens. We evaluated the effects of two environmental pollutants, hexabromocyclododecane (HBCD), 17-β oestradiol (E2) as well as 5-aza 2′ deoxycytidine (5AdC) on global DNA methylation levels (5-methyl 2′ deoxycytidine) in the liver and gonads of the three-spine stickleback (Gasterosteus aculeatus). HBCD at 30 and 300 ng/L of water did not produce statistically significant differences in global genomic methylation in liver of female stickleback. On the other hand, the methylation inhibitor, 5-aza-2′-deoxycytidine, significantly lowered hepatic global methylation levels in these fish by 14% (P<0.05). The naturally occurring oestrogen, 17-β oestradiol (E2) at 100 ng/L also decreased global DNA methylation levels in female liver but this effect was not statistically significant. In contrast, both E2 and 5AdC caused statistically significant (P<0.001 and P<0.01 respectively) global genomic hypermethylation in the gonads of male sticklebacks although the increase seen in the female gonads was not statistically significant. The male gonad effect though unexplained may potentially be an indirect response to hypomethylation in other tissues (such as the liver) and may have important implications regarding oestrogenic effects in fish. The contrasting effects of HBCD and E2 on global DNA methylation in stickleback should contribute to the integrated risk assessment of these environmental chemicals.