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^1,2, Ji Young Kim^1,3, Jin-Yong Chung^1,3, Yoon-Jae Kim^1,2, Ji-Eun Park^1,2, Seunghoon Oh⁴, Yong-Dal Yoon⁵, Ki Soo Yoo^1,2, Young Hyun Yoo^1,2,3, and Jong-Min Kim^1,2,3

¹Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan, Korea; ²Mitochondria Hub Regulation Center, Dong-A University, Busan, Korea; ³Medical Science Research Center, Dong-A University, Busan, Korea; ⁴Department of Physiology, College of Medicine, Dankook University, Cheonan, Korea; ⁵Department of Life Science, College of Natural Sciences, Hanyang University, Seoul, Korea

Advance Publication

Abstract

Background: Bisphenol A (BPA) has been detected in human body fluids, such as serum and ovarian follicular fluids. Several reports indicate that BPA exposure is associated with the occurrence of several female reproductive diseases due to 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 (BW). Serum levels of E2, testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined. Furthermore, the expressions of steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3β-hydroxysteroid dehydrogenase isomerase (3β-HSD), and aromatase cytochrome P450 (P450arom) were analyzed 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. Following BPA exposure, P450arom and StAR protein expression levels significantly decreased in granulosa 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.

Citation: Lee SG, Kim JY, Chung JY, Kim YJ, Park JE, Oh S, Yoon YD, Yoo KS, Yoo YH, Kim JM. Environ Health Perspect (): .doi:10.1289/ehp.1205823

Received: July 27, 2012; Accepted: March 18, 2013; Published: March 19, 2013

Advance Publication

This EHP Advance Publication article has been peer-reviewed, revised, and accepted for publication. The EHP Advance Publication articles are completely citable using the assigned DOI code for the article. This document will be replaced with the copyedited and formatted version as soon as it is available. Through the DOI number used in the citation, you will be able to access this document at each stage of the publication process.