Assessment of zearalenone-induced cell survival and global gene regulation in mouse TM4 Sertoli cells

Zearalenone (ZEA) is a non-steroidal xenoestrogen mycotoxin produced by many Fusarium fungal species, which are common contaminants of cereal crops destined for worldwide human and animal consumption. ZEA has been linked to various male reproduction problems including decreased fertility potential. In this study, the direct impact of ZEA on the immature Sertoli TM4 cell line was evaluated. Results showed that high concentration of ZEA increase reactive oxygen species via the activation of MAPK signaling. Transcriptome analysis was performed on TM4 cell line treated with ZEA and genes involved in sex differentiation (Fgfr2, Igf1, Notch1, Sox9) and extracellular matrix (ECM) formation (Ctgf, Fam20a, Fbn1, Mmp9, Postn, Sparcl1, Spp1) were identified at the center of the functional protein association network suggesting that ZEA could be detrimental to the early steps of Sertoli cell differentiation. 12 samples : 6 controls and 6 treated with Zearalenone

玉米赤霉烯酮（Zearalenone, ZEA）是一类非甾体类外源性雌激素样真菌毒素，由多种镰孢菌属（Fusarium）真菌产生，亦是全球范围内供人类与动物食用的谷类作物的常见污染物。ZEA已被证实与多种雄性生殖功能异常相关，包括生育潜力下降。本研究评估了ZEA对未成熟支持细胞TM4细胞系的直接作用。实验结果显示，高浓度ZEA可通过激活丝裂原活化蛋白激酶（MAPK）信号通路，升高细胞内活性氧水平。研究团队对经ZEA处理的TM4细胞系开展转录组分析，鉴定出位于功能蛋白关联网络核心区域的两类功能基因：其一参与性别分化过程（包含Fgfr2、Igf1、Notch1、Sox9），其二参与细胞外基质（ECM）形成过程（包含Ctgf、Fam20a、Fbn1、Mmp9、Postn、Sparcl1、Spp1）。上述结果提示，ZEA可能对支持细胞分化的早期阶段产生不利影响。本研究共设置12个样本：6个对照组与6个ZEA处理组。