Low concentration of BPA induces mice spermatocytes apoptosis via GPR30
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Chaoliang Wang1,*, Jianxiang Zhang2,*, Qi Li1,*, Tianbiao Zhang1,*, Zishi Deng3,*, Jing Lian1, Donghui Jia1, Rui Li1, Tao Zheng1, Xiaoju Ding1, Fan Yang1, Chao Ma1, Rui Wang1, Weixing Zhang1 and Jian Guo Wen1
1Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
2Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
3No.1 Middle School of Yiyang, Yiyang, Hunan Province, China
*These authors have contributed equally to this work
Jian Guo Wen, email: [email protected]
Keywords: BPA, GPR30, Erk1/2, EGFR-MAPK pathway, spermatocyte apoptosis
Received: December 05, 2016 Accepted: March 13, 2017 Published: April 07, 2017
Bisphenol A (BPA) acts as xenoestrogen and has a great impact on disorders of human reproductive system. However, the mechanism through which BPA can affect human testicular function remains to be identified. GPR30 is a novel membrane estrogen receptor with high-affinity and low-capacity binding to estrogens. We demonstrated that estrogen receptor α (ERα), estrogen receptor β (ERβ) as well as GPR30 are expressed in mouse spermatocyte-derived GC-2 cells using Real-time PCR. We treated the cells with different doses of BPA and found that even low doses of BPA can inhibit GC-2 cell growth using MTT assay. To make sure which receptor is responsible for the biological function of BPA, we used ER down-regulator ICI and indicated that BPA could bind to GPR30. We also observed that BPA was able to induce Erk1/2 phosphorylation in GC-2 cells and proved that this process was mediated by GPR30–related EGFR-MAPK pathway using western blot. By Real-time PCR, we found that the expression of c-Fos was up-regulated and Cyclin D1 gene was down-regulated, in the presence of BPA and ICI. The results of MTT assay, comet assay and flow cytometry indicated that the activation of GPR30 induced by BPA inhibited the cell growth and induced cell apoptosis and ICI, GPR30 siRNA, EGFR inhibitor (AG), and MAPK (PD) inhibitor could partially reverse this effect. Immunohistochemistry on the testis of BPA –damaged mice showed that BPA induced spermatocyte apoptosis without affecting the seminiferous tubules and spermatocyte. In conclusion, BPA triggered spermatocyte apoptosis via GPR30.
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