Bisphenol a exposure during adulthood causes augmentation of follicular atresia and luteal regression by Decreasing 17β-estradiol synthesis via downregulation of aromatase in rat ovary

Seung Gee Lee, Ji Young Kim, Jin Yong Chung, Yoon Jae Kim, Ji Eun Park, Seunghoon Oh, Yong Dal Yoon, Ki Soo Yoo, Young Hyun Yoo, Jong Min Kim

Research output: Contribution to journalArticle

Abstract

Background: Bisphenol A (BPA) has been detected in human body fluids, such as serum and ovarian follicular fluids. Several reports indicated that BPA exposure is associated with the occurrence of several female reproductive diseases resulting from the disruption of steroid hormone biosynthesis in the adult ovary. Objective: We hypothesized that long-term exposure to low concentrations of BPA disrupts 17β estradiol (E2) production in granulosa cells via an alteration of steroidogenic proteins in ovarian cells. Methods: Adult female rats received BPA for 90 days by daily gavage at doses of 0, 0.001, or 0.1 mg/kg body weight. We determined serum levels of E2, testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). We also analyzed the expressions of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase isomerase (3β-HSD), and aromatase cytochrome P450 (P450arom) in the ovary. Results: Exposure to BPA significantly decreased E2 serum concentration, which was accompanied by augmented follicular atresia and luteal regression via increase of caspase-3-associated apoptosis in ovarian cells. After BPA exposure, P450arom and StAR protein levels were significantly decreased in granulosa cells and theca-interstitial (T-I) cells, respectively. However, P450scc and 3β-HSD protein levels remained unchanged. The increase in LH levels appeared to be associated with the decreased synthesis of T in T-I cells after BPA exposure via homeostatic positive feedback regulation. Conclusions: BPA exposure during adulthood can disturb the maintenance of normal ovarian functions by reducing E2. The steroidogenic proteins StAR and P450arom appear to be targeted by BPA.

Original languageEnglish (US)
Pages (from-to)663-669
Number of pages7
JournalEnvironmental Health Perspectives
Volume121
Issue number6
DOIs
Publication statusPublished - Jun 1 2013
Externally publishedYes

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Keywords

  • 17β-estradiol
  • Aromatase
  • Bisphenol a
  • Follicular atresia
  • Luteal regression
  • Ovary
  • Steroidogenic acute regulatory protein

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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