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 testicular ApoA1 and the role of ApoA1 in BPA induced abnormal spermatogenesis, adult male rare minnow Gobiocypris rarus were exposed to 15 μg/L of BPA for 1, 3 and 5 weeks. Results showed that BPA could significantly affect testicular ApoA1 mRNA and protein levels, testicular cholesterol levels, plasmatic sex hormone levels and the integrity of sperm head membrane. The main mechanism of BPA regulating ApoA1 expression is to alter Esr recruitment and CpG sites DNA methylation in ApoA1 promoter. 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.

双酚A（BPA）是一种广为人知的增塑剂，广泛分布于水生环境中。BPA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研究BPA影响繁殖的机制。载脂蛋白 A1 (ApoA1) 是高密度脂蛋白 (HDL) 的主要成分，在胆固醇逆向转运 (RCT) 中起关键作用。本研究为探讨 BPA 对睾丸ApoA1的影响及其分子机制以及ApoA1在 BPA 诱导异常精子发生中的作用，将成年雄性稀有鲦鱼Gobiocypris rarus暴露于 15 μg/L BPA 1、3 和 5周。结果表明，BPA 可显着影响睾丸ApoA1mRNA 和蛋白质水平、睾丸胆固醇水平、血浆性激素水平和精子头膜的完整性。BPA 调节ApoA1表达的主要机制是改变ApoA1启动子中的Esr 募集和 CpG 位点 DNA 甲基化。诱导的 ApoA1 上调高密度脂蛋白胆固醇水平并增强 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 BPA 干扰精子发生的机制。