Bisphenol A decreases progesterone synthesis by disrupting cholesterol homeostasis in rat granulosa cells

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.