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 Lee1,2, Ji Young Kim1,3, Jin-Yong Chung1,3, Yoon-Jae Kim1,2, Ji-Eun Park1,2, Seunghoon Oh4, Yong-Dal Yoon5, Ki Soo Yoo1,2, Young Hyun Yoo1,2,3, and Jong-Min Kim1,2,3
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
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
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