Global and cyp19a1a gene specific DNA methylation in gonads of adult rare minnow Gobiocypris rarus under bisphenol A exposure

Abstract

As a weak estrogenic chemical, bisphenol A (BPA) has been extensively studied for reproductive toxicity and the effects on the steroidogenesis. In the present study, we aim to explore the effects of BPA on epigenetic modification in rare minnow Gobiocypris rarus. We have detected the global and cyp19a1a gene specific DNA methylation in gonads of adult G. rarus under BPA exposure. The global DNA methylation level was significantly increased in testis of the male fish exposed to BPA for 7 days, and it was significantly increased in the ovary following 35-days exposure. DNA methyltransferases (DNMTs) catalyze the transfer of a methyl moiety from S-adenosyl-l-methionine to the cytosine of a CpG dinucleotide. The alteration of the detected dnmts mRNA expression could affect the global DNA methylation levels following 15μg/L BPA exposure. Cytochrome P450 aromatase (CYP19A1A), is responsible for the conversion of androgens into estrogens, which plays a vital role in estrogen synthesis in gonads. In the present study, the methylation level of ovarian cyp19a1a gene was significantly suppressed and stimulated by 7- and 35-day BPA exposure, respectively. There was a significant negative correlation between cyp19a1a mRNA expression and methylation levels of the four CpGs at the 5' flanking region in the ovary of adult G. rarus following BPA exposure. So we hypothesize that there are some association between the reproductive toxicity of BPA and the global DNA methylation under BPA exposure. And the alteration of cyp19a1a expression in female G. rarus by BPA might attribute to the change of its DNA methylation status.

Keywords: Bisphenol A; Cytochrome P450 aromatase; DNA methylation; DNA methyltransferase; Gobiocypris rarus.