Transgenerational effects of BPA on female reproduction

• Published in: The Science of the total environment 2019-10, Vol.685, p.1294-1305
• Main Authors: Santangeli, Stefania, Consales, Claudia, Pacchierotti, Francesca, Habibi, Hamid R., Carnevali, Oliana
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - toxicity; Bisphenol A; DNA Methylation; Epigenesis, Genetic; Female; Female reproduction; Histone modification; Histones; Phenols - toxicity; Promoter Regions, Genetic; Reproduction - drug effects; Transgenerational inheritance; Water Pollutants, Chemical - toxicity; Zebrafish
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2019.06.029

Bisphenol A (BPA) is an abundant environmental contaminant and studies have shown the presence of BPA 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 transgenerational effect, an epigenetic mark should be mitotically and meiotically stable without reprogramming 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 several genes involved in female reproduction were measured in adult and in 24 hpf embryos up to F3 generation. Exposure to BPA affected adult female fertility up to F2 generation. In F0, F1 and F2 ovaries transcript levels for several genes involved in reproduction, including esr, star, lhcgr and fshr were affected. To investigate epigenetic mechanisms of gene expression modulation, we studied promoter DNA methylation. Among genes involved in gonadal differentiation, amh transcript level was reduced in 24 hpf embryos, up to the F3 generation. Variation in amh transcript level was associated with hyper-methylation of its promoter and changes in H3K4me3/H3K27me3 enrichment, coherent with gene silencing. The findings provide evidence for transgenerational effects of BPA in zebrafish and demonstrate that amh is susceptible to stable epigenetic alterations. Transgenerational effects of BPA on female reproductive physiology. [Display omitted] •BPA's effects show a transgenerational transmission via maternal route.•Transgenerational transmission involves both histone modification and DNA methylation.•Amh hypermethylation shows a stable transmission throughout generations.