BPA's transgenerational disturbance to transcription of ovarian steroidogenic genes in rare minnow Gobiocypris rarus via DNA and histone methylation

Abstract

As a well-known estrogenic endocrine disruptor, bisphenol A (BPA) is of utmost concern since it is reported with harmful effects on animal reproduction. However, the adverse effects on progeny after parental BPA exposure are largely unknown in fishes. To investigate the epigenetic effects of BPA on progeny gonadal development, parental rare minnow (Gobiocypris rarus) were exposed to BPA (15 μg L−1) for two months, then were purged in clean water for one, two or three months, respectively. From the second month, parents were mated once a month and the offspring were reared to 5 months old. Results showed that parental BPA exposure inhibited the ovary development of the offspring by reducing the number of mature oocytes while the transcripts of steroidogenic genes (cyp11a1, cyp17a1, cyp19a1a and star) were significantly affected. And the negative effects of parental BPA exposure on the offspring were reversible. The DNA methylation and histone trimethylation levels (H3K9me3 and H3K27me3) together with the expression of dnmts (dnmt1, dnmt5 and dnmt7) and histone methyltransferase genes (setdb1, setdb2 and ezh2) were significantly altered in the ovaries of the 5-month old offsprings. BPA interfered the expression of steroidogenic genes by altering histone recruitment in star (H3K4me3 and H3K9me3), in cyp11a1 and cyp17a1 (H3K9me3 and H3K27me3), as well as in cyp19a1a (H3K4me3, H3K9me3 and H3K27me3). In addition, altering of DNA methylation at CpG site caused by BPA exposure involved in the regulation of star, cyp17a1 and cyp19a1a expression. These results suggest that BPA transgenerationally imposes detriment to reproduction and the epigenetic changes in DNA methylation and histone trimethylation might account for steroidogenic genes expression.