College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.
Environ Toxicol. 2023 Feb;38(2):278-288. doi: 10.1002/tox.23694. Epub 2022 Oct 26.
Zearalenone (ZEA), a common mycotoxin in animal feed, is harmful to public health and causes huge economic losses. The potential target proteins of ZEA and its derivatives were screened using the PharmMapper database and the related genes (proteins) of the testis were obtained from Genecards. We obtained 144 potential targets of ZEA and its derivatives related to the testis using Venn diagrams. The PPI analysis showed that ZEA had the most targets in testis, followed by ZAN, α-ZAL, β-ZEL, α-ZEL, and β-ZAL. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses evaluated the metabolic and cancer pathways. We further screened four hub genes: RAC3, CCND1, EP300, and CTNNB1. Eight key biological processes were obtained by GO analysis, and four important pathways were identified by KEGG analysis. Animal and cell experimental results confirmed that ZEA could inhibit the expression of four key KEGG pathway protein components and four hub proteins that interfere with cell adhesion by inhibiting the focal adhesion structure of the testis, Leydig cells, and Sertoli cells. Collectively, our findings reveal that the destruction of the focal adhesion structure in the testis is the mechanism through which ZEA damages the male reproductive system.
玉米赤霉烯酮（ZEA）是一种常见的动物饲料中的真菌毒素，对公共健康有害，并造成巨大的经济损失。本研究使用 PharmMapper 数据库筛选 ZEA 及其衍生物的潜在靶蛋白，并从 Genecards 获得睾丸的相关基因（蛋白）。我们使用 Venn 图获得了 144 个与睾丸相关的 ZEA 及其衍生物的潜在靶蛋白。蛋白质-蛋白质相互作用（PPI）分析表明，ZEA 在睾丸中有最多的靶蛋白，其次是 ZAN、α-ZAL、β-ZEL、α-ZEL 和 β-ZAL。京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析评估了代谢和癌症途径。我们进一步筛选了四个枢纽基因：RAC3、CCND1、EP300 和 CTNNB1。GO 分析得到了八个关键的生物学过程，KEGG 分析确定了四个重要的途径。动物和细胞实验结果证实，ZEA 可以通过抑制睾丸、间质细胞和支持细胞的粘着斑结构来抑制四个关键 KEGG 途径蛋白成分和四个干扰细胞粘着的枢纽蛋白的表达，从而损害男性生殖系统。总之，我们的研究结果表明，睾丸粘着斑结构的破坏是 ZEA 损害男性生殖系统的机制。
