University of Novi Sad, Faculty of Sciences, Department of Biology and Ecology, Serbia.
University of Novi Sad, Faculty of Technical Sciences, Department of Environmental Engineering and Occupational Safety and Health, Serbia.
Mol Cell Endocrinol. 2018 Feb 5;461:55-63. doi: 10.1016/j.mce.2017.08.013. Epub 2017 Aug 30.
Bisphenol A (BPA) is an endocrine disruptor used in a variety of consumer products. Exposure to BPA leads to alterations in steroidogenesis of ovarian granulosa cells. Here, we analyzed the mechanism by which BPA alters progesterone biosynthesis in immature rat granulosa cells. BPA increased expression of steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase in granulosa cells; however, BPA prevented the basal and the FSH-induced progesterone production. BPA caused sequestration of cholesterol to the perinuclear area, as evident by the Filipin staining. BPA decreased mRNA expression of ATP binding cassette transporter-A1 (Abca1) and increased level of sterol regulatory element binding protein 1. Addition of exogenous cell-permeable cholesterol restored the effect of BPA on Abca1 and Star mRNA expression and partially reversed BPA's effect on progesterone production. These results indicate that exposure to BPA disrupts cholesterol homeostasis leading to decreased progesterone production in immature rat granulosa cells.
双酚 A（BPA）是一种用于各种消费产品的内分泌干扰物。接触 BPA 会导致卵巢颗粒细胞的甾体生成发生改变。在这里，我们分析了 BPA 改变未成熟大鼠颗粒细胞中孕激素生物合成的机制。BPA 增加了颗粒细胞中类固醇急性调节蛋白（StAR）、胆固醇侧链裂解酶和 3β-羟甾脱氢酶的表达；然而，BPA 阻止了基础和 FSH 诱导的孕激素产生。BPA 导致胆固醇向核周区的隔离，Filipin 染色明显。BPA 降低了 ABCA1 转运蛋白（Abca1）的 mRNA 表达水平，增加了固醇调节元件结合蛋白 1 的水平。添加细胞通透性胆固醇恢复了 BPA 对 Abca1 和 Star mRNA 表达的影响，并部分逆转了 BPA 对孕激素产生的影响。这些结果表明，接触 BPA 破坏了胆固醇稳态，导致未成熟大鼠颗粒细胞中孕激素产生减少。
