Journal
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
Volume 59, Issue -, Pages 66-73Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.etap.2018.03.001
Keywords
Bisphenol A; Fisetin; Progesterone; Granulosa cells; Steroidogenesis; Steroidogenic enzyme expression
Funding
- Scientific Grant Agency VEGA [VEGA 2/0198/15]
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In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 mu M, 100 mu M) and the flavonoid fisetin (1, 10, 25, 50 mu M), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs. The mechanisms of the inhibitory effects of the combinations included a significant down-regulation of the key steroidogenesis-related genes (STAR, CYP11A1, HSD3B). Our findings suggest for the first time that fisetin might interfere with ovarian steroidogenesis, and might not have beneficial but rather aggravating effects in terms of modulating progesterone synthesis altered by high concentrations of BPA.
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