Abstract
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.
Highlights
It has been demonstrated that many man-made chemicals presented in food and environment are hormone-like pollutants, which can disrupt the endocrine systems of animals and are called environmental endocrine disrupting chemicals (EDCs) [1,2,3]
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 observed that Bisphenol A (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
Summary
It has been demonstrated that many man-made chemicals presented in food and environment are hormone-like pollutants, which can disrupt the endocrine systems of animals and are called environmental endocrine disrupting chemicals (EDCs) [1,2,3]. BPA is a high production volume chemical used in the manufacture of polycarbonate plastics and epoxy resins, which can be used in baby and water bottles, food container linings, beverage cans, medical tubing, dental fillings and other applications [7, 8]. Once it has contaminated the environment, BPA is expected to be more persistent in water and soil [9]. Dietary ingestion is considered the primary source of general population exposure to BPA. BPA exposure is widespread in the general populations
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