Transgenerational effects of BPA on female reproduction

Bisphenol A (BPA) is consistently present in the environment and studies have shown BPA presence in the urine of over 90% of population tested in Canada and USA. In addition to its reported harmful effects, there is concern for its transgenerational effects. For a compound to induce a transgenerational effect, an epigenetic mark should be mitotically and meiotically stable and should not be reprogrammed in primordial germ cells and post fertilization embryos. In the present study, female zebrafish were treated with an environmental dose (20 μg/L) of BPA and then crossed with untreated males. To assess epigenetic effects, transcript levels of a number of genes involved in female reproduction were measured in adult and in 24 hpf embryos up to F3 generation. The results demonstrate that BPA exposure affects female adult fertility up to F2. In F0, F1 and F2 ovaries the transcript levels of several genes involved in reproduction, including esr, star, lhcgr and fshr were affected.In order to investigate if epigenetic mechanisms were involved in gene expression modulation, we studied promoter DNA methylation. In 24 hpf embryos, among genes involved in gonadal differentiation, amh transcript level was reduced up to the F3 generation, which was associated with a hyper-methylation of its promoter and with changes in H3K4me3/H3K27me3 enrichment, coherent with gene silencing.The findings provide information on transgenerational effects of BPA in zebrafish and demonstrate that amh is susceptible to transgenerationally stable, functional, epigenetic alterations.Transgenerational effects of BPA on female reproductive physiology.