Abstract
Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters—as well as that of kat6a—an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.
Highlights
We demonstrated that the coco-treatment with epigallocatechin gallate (EGCG) counteracted the negative effects of bisphenol A (BPA) on early zebrafish emtreatment with counteracted the negative effects of on early zebrafish embryos: bryos: the expression of estrogen receptors and the histone acetylation returned to basal the expression of estrogen receptors and the histone acetylation returned to basal levels, levels, allowing proper embryonic development [18]
Concerning the expression of transcription factors, the results showed an increase in the expression of the basic helix-loop-helix transcription factor, hand2, in embryos at 24 hpf, when fathers were exposed to 2000 μg/L BPA; in contrast the expression of esr2b, and hand2 promoters in the progeny from control males and males exposed to BPA (D)
Concerning the expression of transcription factors, the results showed an increase in the expression of the basic helix-loop-helix transcription factor, hand2, in embryos at 24 hpf, when fathers were exposed to 2000 μ g/L BPA; in contrast the expression of gata5, gata4, and bmp4 remained steady in remained embryos obtained
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Congenital heart defects (CHDs) represent the main group of congenital anomalies and they are the leading cause of spontaneous abortions [1]. The worldwide incidence of CHDs is around 8 per 1000 live births, but this number keeps increasing and strongly depends on the country [2,3]. Several studies concluded that disruption of both male and female reproductive systems, triggered by occupational exposure to some chemicals during the periconceptional period, led to congenital malformations in the generation [7,8,9,10]
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