Bisphenol A regulates apolipoprotein A1 expression through estrogen receptors and DNA methlylation and leads to cholesterol disorder in rare minnow testis
Bisphenol A regulates apolipoprotein A1 expression through estrogen receptors and DNA methlylation and leads to cholesterol disorder in rare minnow testis
复制标题
双酚 A 通过雌激素受体和 DNA 甲基化调节载脂蛋白 A1 表达，导致罕见米诺睾丸胆固醇紊乱
DOI：
10.1016/j.aquatox.2021.105999
复制
发表时间：
2021
影响因子：
4.5
通讯作者：
Bichun Li
中科院分区：
文献类型：
--
作者：
Yingying Zhang;Meng Zhang;Zhu Zhu;Hui Yang;Wenzhi Wei;Bichun Li
双酚A （BPA）是一种广泛存在于水生环境中的增塑剂。双酚a对生殖有许多不利影响。然而，很少有研究从脂质代谢的角度探讨BPA影响生殖的机制。载脂蛋白A1 （ApoA1）是高密度脂蛋白（HDL）的主要组成部分，在胆固醇逆向转运（RCT）中起关键作用。为了研究BPA对睾丸apoa1的影响及其分子机制，以及apoa1在BPA诱导的异常精子发生中的作用，本研究采用15 μg/L的双酚a对成年雄性珍稀虾虎鱼（gobiocypris rarar）进行了1、3、5周的暴露。结果表明，BPA可显著影响睾丸apoa1mrna和蛋白水平、睾丸胆固醇水平、血浆性激素水平和精子头膜完整性。BPA调节apoa1表达的主要机制是改变apoa1启动子内Esr募集和CpG位点DNA甲基化。诱导ApoA1上调高密度脂蛋白胆固醇水平，增强RCT，最终降低睾丸游离胆固醇水平。这可能是BPA诱发性激素紊乱和精子头膜损伤的关键机制。本研究从胆固醇转运的角度揭示了双酚a干扰精子发生的机制。
Bisphenol A (BPA) is a well-known plasticizer that widely distributed in the aquatic environment. BPA has many adverse effects on reproduction. However, few studies have investigated the mechanism of BPA affecting reproduction from the perspective of lipid metabolism. Apolipoprotein A1 (ApoA1) is the major component of high-density lipoprotein (HDL), and plays critical roles in reverse cholesterol transport (RCT). In this study, in order to investigate the effect and molecular mechanism of BPA on testicularApoA1and the role ofApoA1in BPA induced abnormal spermatogenesis, adult male rare minnowGobiocypris raruswere exposed to 15 μg/L of BPA for 1, 3 and 5 weeks. Results showed that BPA could significantly affect testicularApoA1mRNA and protein levels, testicular cholesterol levels, plasmatic sex hormone levels and the integrity of sperm head membrane. The main mechanism of BPA regulatingApoA1expression is to alter Esr recruitment and CpG sites DNA methylation inApoA1promoter. The induced ApoA1 up-regulated high density lipoprotein cholesterol levels and enhanced RCT, and finally decreased the testicular free cholesterol levels. This is likely a key mechanism by which BPA induces sex hormone disorder and sperm head membrane damage. The present study reveals the mechanism by which BPA interferes with spermatogenesis from the perspective of cholesterol transport.