Xu Ming-Long, Hu Jin, Guo Bao-Ping, Niu Ya-Ru, Xiao Cheng, Xu Yin-Xue
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.
Environ Toxicol. 2016 Dec;31(12):1731-1739. doi: 10.1002/tox.22175. Epub 2015 Oct 13.
Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016.
玉米赤霉烯酮（ZEA）是一种主要由镰刀菌产生的非甾体雌激素类霉菌毒素。ZEA会导致生殖紊乱，并且在动物体内具有细胞毒性和基因毒性；然而，关于导致ZEA毒性的分子机制却知之甚少。支持细胞是支持生精细胞发育的体细胞。本研究的目的是探究ZEA对大鼠支持细胞增殖、凋亡和坏死的影响，以揭示ZEA细胞毒性背后的信号通路。CCK8检测表明，ZEA以剂量依赖的方式降低大鼠支持细胞的增殖，而流式细胞术显示ZEA会导致凋亡和坏死。免疫印迹显示，ZEA处理以剂量依赖的方式增加了Bax/Bcl-2的比值，以及FasL和半胱天冬酶-3、-8和-9的表达。总体而言，这些数据表明ZEA通过外源性和内源性凋亡途径诱导大鼠支持细胞凋亡和坏死。本研究为ZEA表现出细胞毒性的分子机制提供了新的见解。© 2015威利期刊公司。《环境毒理学》31: 1731 - 1739，2016年。
