Exposure of preimplantation embryos to low-dose bisphenol A impairs testes development and suppresses histone acetylation of StAR promoter to reduce production of testosterone in mice
Exposure of preimplantation embryos to low-dose bisphenol A impairs testes development and suppresses histone acetylation of StAR promoter to reduce production of testosterone in mice
复制标题
植入前胚胎暴露于低剂量双酚 A 会损害睾丸发育并抑制 StAR 启动子的组蛋白乙酰化，从而减少小鼠睾酮的产生
DOI：
10.1016/j.mce.2016.03.009
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发表时间：
2016-05-15
影响因子：
4.1
通讯作者：
Chen, Ling
中科院分区：
文献类型：
--
作者：
Hong, Juan;Chen, Fang;Chen, Ling
研究表明，双酚A（BPA）是一种潜在的内分泌干扰物和睾丸毒物。本研究旨在探讨低剂量BPA暴露对雄性胚胎早期生殖发育的影响及其机制。雌性小鼠在妊娠第1-5天口服BPA（20 μ g/kg/天）。雄性后代在PND 10、20、24、35或PND 50处以安乐死。我们发现，在植入前暴露于BPA的小鼠（BPA-小鼠）表现出睾丸发育迟缓，睾酮水平降低。在PND 35，BPA-小鼠生精小管的直径和上皮高度降低。BPA-小鼠在PND 50时，不同时期的生精细胞数量显著减少。BPA小鼠从PND 24开始血清和睾丸睾酮水平持续降低，而GnRH mRNA在PND 35和PND 50显著增加。BPA-小鼠睾丸星星和P450 SCC的表达在PND 35和PND 50时也相对于对照组降低。进一步的分析发现，星星启动子中组蛋白H3和H3 K14乙酰化（Ac-H3和H3 K14 ac）的水平相对于对照小鼠降低，而P450 SCC启动子中Ac-H3的水平在各组之间没有显著差异。这些结果提供了证据表明，在植入前胚胎中暴露于BPA通过减少星星启动子的组蛋白乙酰化以破坏睾丸睾酮合成来延缓睾丸发育。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Previous studies have shown that bisphenol A (BPA) is a potential endocrine disruptor and testicular toxicant. The present study focused on exploring the impact of exposure to low dose of BPA on male reproductive development during the early embryo stage and the underlying mechanisms. BPA (20 mu g/kg/day) was orally administered to female mice on days 1-5 of gestation. The male offspring were euthanized at PND10, 20, 24, 35 or PND50. We found that the mice exposed to BPA before implantation (BPA-mice) displayed retardation of testicular development with reduction of testosterone level. The diameter and epithelium height of seminiferous tubules were reduced in BPA-mice at PND35. The numbers of spermatogenic cells at different stages were significantly reduced in BPA-mice at PND50. BPA-mice showed a persistent reduction in serum and testicular testosterone levels starting from PND24, whereas GnRH mRNA was significantly increased at PND35 and PND50. The expressions of testicular StAR and P450scc in BPA-mice also decreased relative to those of the controls at PND35 and PND50. Further analysis found that the levels of histone H3 and H3K14 acetylation (Ac-H3 and H3K14ac) in the promoter of StAR were decreased relative to those of control mice, whereas the level of Ac-H3 in the promoter of P450scc was not significantly different between the groups. These results provide evidence that exposure to BPA in preimplantation embryo retards the development of testes by reducing histone acetylation of the StAR promoter to disrupt the testicular testosterone synthesis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.