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Abstract
Bisphenol A (BPA), a typical environmental endocrine-disrupting chemical, induces epigenetic inheritance. Whether histone acetylation plays a role in these effects of BPA is largely unknown. Here, we investigated histone acetylation in male rats after long-term exposure to a ‘safe’ dose of BPA. Twenty adult male rats received either BPA (50 μg/kg·bw/day) or a vehicle diet for 35 weeks. Decreased protein lysine-acetylation levels at approximately ~17 kDa and ~25 kDa, as well as decreased histone acetylation of H3K9, H3K27 and H4K12, were detected by Western blot analysis of testes from the treated rats compared with controls. Additionally, increased protein expression of deacetylase Sirt1 and reduced binding of Sirt1, together with increased binding of estrogen receptor β (ERβ) to caveolin-1 (Cav-1), a structural protein component of caveolar membranes, were detected in treated rats compared with controls. Moreover, decreased acetylation of Cav-1 was observed in the treated rats for the first time. Our study showed that long-term exposure to a ‘safe’ dose of BPA reduces histone acetylation in the male reproductive system, which may be related to the phenotypic paternal-to-offspring transmission observed in our previous study. The evidence also suggested that these epigenetic effects may be meditated by Sirt1 via competition with ERβ for binding to Cav-1.
Highlights
Paternal BPA exposure disrupts male rat fertility and alters functions in the F1 generation[6,7,8,9]
In addition to decreased histone acetylation, we further detected a significant increase in the expression of histone deacetylase Sirt[1] in the testes of BPA-treated rats compared with controls (P < 0.05; Fig. 3)
A similar adult male rat model was used, and, compared with the control group, a remarkable reduction in acetylation of H3 (Lys[9] and Lys27) and H4 at lysine 12 were detected in the testes (Fig. 2) where spermatogenesis occurs, and the majority of histones were replaced with protamines[27]
Summary
Paternal BPA exposure disrupts male rat fertility and alters functions in the F1 generation[6,7,8,9]. Cav-1 binds with estrogen receptors (ER), including ERα,ERβ,and the G protein-coupled estrogen receptor (GPER)[22,23], and these receptors all bind to BPA with different affinities[24,25] As both Sirt[1] and ERs bind to Cav-1, an interplay between estrogen signaling and Sirt[1] within the caveolae may exist. The aim of this study was to determine whether long-term exposure to a ‘safe’ dose of BPA induces alteration of protein acetylation in the paternal reproductive system and to explore the possible mechanisms. To our knowledge, this is the first report demonstrating that essential molecules, including estrogen receptors, Cav[1], and Sirt[1], are involved in this epigenetic modification
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