title: Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles.
abstract: Bisphenol A (BPA) is the backbone of polycarbonate plastic products and the epoxy resin lining of aluminum cans. Previous studies have shown that exposure to BPA decreases sex steroid hormone production in mouse antral follicles. The current study tests the hypothesis that BPA first decreases the expression levels of the steroidogenic enzyme cytochrome P450 side-chain cleavage (Cyp11a1) and steroidogenic acute regulatory protein (StAR) in mouse antral follicles, leading to a decrease in sex steroid hormone production in vitro. Further, the current study tests the hypothesis that these effects are acute and reversible after removal of BPA. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased expression of Cyp11a1 and StAR beginning at 18h and 72h, respectively, compared to controls. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased progesterone levels beginning at 24h and decreased androstenedione, testosterone, and estradiol levels at 72h and 96h compared to controls. Further, after removing BPA from the culture media at 20h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48h and 72h, respectively. Additionally, expression of StAR and levels of androstenedione, testosterone, and estradiol never decreased compared to controls. These data suggest that BPA acutely decreases expression of Cyp11a1 as early as 18h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure.
authors.affiliation: 2001 South Lincoln Ave, 3211 VMBSB, University of Illinois, Urbana, IL 61802, USA. peretz@illinois.edu
authors.forename: Jackye
authors.initials: J
authors.lastname: Peretz
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Flaws
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects / Q000201:enzymology*; D010636:Phenols / Q000494:pharmacology*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013256:Steroids / Q000096:biosynthesis*; D000098682:Steroidogenic Acute Regulatory Protein; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D002786:Cholesterol Side-Chain Cleavage Enzyme; D004968:Estrogens, Non-Steroidal; D012739:Gonadal Steroid Hormones; D010636:Phenols; D010750:Phosphoproteins; D013256:Steroids; D000098682:Steroidogenic Acute Regulatory Protein; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Antral follicle; Bisphenol A; Cyp11a1; Reversible; Steroidogenesis