Bisphenol A and genistein have opposite effects on adult chicken ovary by acting on ER alpha/Nrf2-Keap1-signaling pathway

文献类型： 外文期刊

第一作者： Gao, Zhangshan

作者： Gao, Zhangshan;Gao, Xiaona;Fan, Wentao;Liu, Shuhui;Li, Mengcong;Miao, Yufan;Ding, Chenchen;Tang, Zhihui;Yan, Liping;Song, Suquan;Liu, Guangliang;Shi, Xizhi

作者机构：

关键词： Bisphenol A; Genistein; Adult chicken ovary; Oxidative stress; ER alpha; Nrf2-Keap1

期刊名称：CHEMICO-BIOLOGICAL INTERACTIONS （ 影响因子：5.194； 五年影响因子：4.611 ）

ISSN： 0009-2797

年卷期： 2021 年 347 卷

页码：

收录情况： SCI

摘要： The reproductive toxicity of endocrine-disrupting chemicals has become a matter of great concern. However, the potential toxicological mechanism of typical environmental estrogens, bisphenol A (BPA) and genistein (GEN), on adult ovary remains ambiguous. In this study, we used laying hens as the experimental model and aimed to clarify the effect of long-term exposure to safe reference doses of BPA and GEN on adult ovary. Results demonstrated that 1/10 no-observable-adverse effect-level dose (1/10 NOAEL, 500 mu g/kg body weight [bw]/day) of BPA significantly reduced the production performance and caused the degeneration of follicles and stromal cells and the increase of atretic follicles. Moreover, 1/10 NOAEL dose of BPA undermined the redox homeostasis of the ovary through activating Keap1 and suppressing the Nrf2-signaling pathway (Nrf2, NQO1, and HO-1). On the contrary, GEN (20, 40 mg/kg bw/day) dramatically improved the antioxidant capacity of the ovary by regulating the Nrf2-Keap1 pathway, enhancing the activities of antioxidant-related enzymes (CAT, GSH-Px, and T-SOD), and inhibiting the excessive accumulation of lipid peroxidation products (MDA). Parallel in vitro studies confirmed that the differential role of BPA and GEN on ovarian redox balance was directly mediated by Nrf2-Keap1 antioxidant system. And GEN could ameliorate BPA-induced oxidative stress. Importantly, our research found that exposure to BPA and GEN altered estrogen receptor alpha (ER alpha) expression in the ovary. And the use of specific ER alpha agonist/antagonist confirmed that BPA and GEN have opposite regulatory effects on the Nrf2-Keap1 pathway by targeting ER alpha.

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