Journal
TOXICOLOGY LETTERS
Volume 226, Issue 1, Pages 81-89Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2014.01.035
Keywords
GPR30; Sertoli cell; TM4; Estrogen receptor alpha/beta (ER alpha/beta); Male; Reproduction
Categories
Funding
- National Natural Science Foundation of China [31101071, 81302317]
- National Basic Research Program of China (973 Program) [2011CB9358003]
- Fundamental Research Funds for the Central Universities (Sun Yat-sen University) [12ykpy09]
- Science and Technology Planning Project of Guangdong Province, China [2012B031500005]
- Seed Collaborative Research Fund from the State Key Laboratory in Marine Pollution [SCRF0003]
- National Science and Engineering Research Council of Canada [326415-07]
- program of High Level Foreign Experts [GDW20123200120]
- State Administration of Foreign Experts Affairs, the P.R. China
- Chinese Academy of Sciences
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Sertoli cells play a pivotal role in supporting proliferation of germ cells and differentiation during spermatogenesis in mammals. Nanomolar concentrations of Bisphenol A (BPA) can significantly stimulate the proliferation of mouse immature Sertoli (TM4) cells. However, mechanisms by which BPA caused these effects were still unclear. In the present study, an inverse U-shaped curve was observed when treating TM4 cells with increasing doses of BPA: 1 to 10 nM BPA significantly stimulated the proliferation of TM4 cells and increased the proportion of cells in S phase; >1 mu M BPA caused lesser proliferation of cells. Exposure of TM4 cells to G15 or ICI 182,780, which are specific antagonists of GPR30 and estrogen receptor alpha/beta (ER alpha/beta), respectively, abolished BPA-induced proliferation of cells, which suggests that both GPR30 and ER alpha/beta were involved in the observed effects of BPA. Furthermore, exposure to BPA caused rapid (5 min) activation of ERK1/2 via both GPR30 and ER alpha/beta. Blocking the GPR30/EGFR signal transduction pathway by antagonists suppressed both phosphorylation of ERK and BPA-induced cell proliferation. BPA up-regulated mRNA and protein expression of GPR30 in a concentration-dependent manner. In summary, the results reported here indicated that activating ERK1/2 through GPR30 and ER alpha/beta is involved in low doses of BPA that promoted growth of Sertoli TM4 cells. The GPR30/EGFR/ERK signal is the downstream transduction pathway in BPA-induced proliferation of TM4 Sertoli cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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