Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles

Jackye Peretz, Jodi A. Flaws

Research output: Contribution to journalArticle

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 18. h and 72. h, respectively, compared to controls. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased progesterone levels beginning at 24. h and decreased androstenedione, testosterone, and estradiol levels at 72. h and 96. h compared to controls. Further, after removing BPA from the culture media at 20. h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48. h and 72. h, 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 18. h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24. h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72. h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalToxicology and Applied Pharmacology
Volume271
Issue number2
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Down-Regulation
Androstenedione
Progesterone
Testosterone
Estradiol
Gonadal Steroid Hormones
Antral
bisphenol A
Plastic products
Epoxy Resins
Level control
Aluminum
Linings
Cytochrome P-450 Enzyme System
Culture Media
steroidogenic acute regulatory protein
Enzymes

Keywords

  • Antral follicle
  • Bisphenol A
  • Cyp11a1
  • Reversible
  • Steroidogenesis

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Bisphenol A down-regulates rate-limiting Cyp11a1 to acutely inhibit steroidogenesis in cultured mouse antral follicles. / Peretz, Jackye; Flaws, Jodi A.

In: Toxicology and Applied Pharmacology, Vol. 271, No. 2, 01.09.2013, p. 249-256.

Research output: Contribution to journalArticle

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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 18. h and 72. h, respectively, compared to controls. Exposure to BPA (10μg/mL and 100μg/mL) significantly decreased progesterone levels beginning at 24. h and decreased androstenedione, testosterone, and estradiol levels at 72. h and 96. h compared to controls. Further, after removing BPA from the culture media at 20. h, expression of Cyp11a1 and progesterone levels were restored to control levels by 48. h and 72. h, 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 18. h and this reduction in Cyp11a1 may lead to a decrease in progesterone production by 24. h, followed by a decrease in androstenedione, testosterone, and estradiol production and expression of StAR at 72. h. Therefore, BPA exposure likely targets Cyp11a1 and steroidogenesis, but these effects are reversible with removal of BPA exposure.",
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