The interference effects of bisphenol A on the synthesis of steroid hormones in human ovarian granulosa cells.

Abstract

Numerous studies have shown that endocrine-disrupting chemicals are one of the important pathogenic factors in women with polycystic ovary syndrome. Our previous study has revealed that bisphenol A (BPA) can cause steroid hormone imbalance, polycystic ovary, and estrus cycle disorder. In this study, we aimed to explore the effect of BPA, a typical environmental estrogen, on the synthesis of steroid hormones in human ovarian granulosa KGN cells. Exposure of KGN cells to BPA (0.5, 5, 50, and 500 μg/L) resulted in the decrease of progesterone (P), estradiol (E2), and the ratio of estradiol to testosterone (E2/T). BPA affected the expression of genes related to steroid hormone synthesis in KGN cells, including the decreased expression of the steroidogenic acute regulatory protein, ferredoxin, and ferredoxin reductase genes during progesterone synthesis; upregulating the expression of cytochrome p450 oxidoreductase gene associated with E2 and T synthesis; and the downregulated cytochrome P450 family 1 subfamily A member 1 and cytochrome P450 family 1 subfamily B member 1 in E2 degradation. BPA also reduced the expression of stimulatory G proteins (GS) in follicle-stimulating hormone receptor (FSHR)/GS/adenylate cyclase (AC) signaling pathway. In summary, our research has demonstrated that environment-relevant level of BPA exposure leads to steroid hormone synthesis disorder in human ovarian granulosa cells, which might cause the reduction of gene expression in hormone synthesis and the suppression of the FSHR/GS/AC signaling pathway.