Abstract:
T-2 toxin (T-2), an A-type mono mycotoxin produced by various Fusarium species, disrupts DNA/RNA and protein synthesis upon entering the body, resulting in pathological conditions in various tissues/organs and posing a significant threat to human and animal health. However, the mechanisms underlying its toxicity remain unclear. With the goal of learning how T-2 affects reproduction in animals, we utilized primary porcine ovarian granulosa cells (pGCs) as a carrier in vitro and constructed concentration models for analyzing cell morphology and RNA-sequencing (RNA-seq). Our findings showed that T-2 could influence pGCs morphology, induce cell cycle arrest, and promote apoptosis in a dose-dependent manner. The results of RNA-seq analyses indicated that a total of 8216 genes exhibited significant differential expression (DEG) following T-2 treatment, of which 4812 were observed to be down-regulated and 3404 were up-regulated. The DEGs following T-2 toxin treatment of pGCs had a notable impact on many metabolic pathways such as PI3K-Akt, Ras, MAPK, and apoptosis, which in turn altered important physiological processes. Gene set enrichment analysis (GSEA) indicated that the differences in the harmful effects of T-2 might be caused by the varying control of cellular processes and the pathway responsible for steroid metabolism. These results present further insights regarding the mechanism of T-2 action on sow reproductive toxicity, enhance our understanding of T-2 reproductive toxicological effects, and lay a theoretical foundation for the judicious prevention of T-2-induced reproductive toxicity.
摘要:
T-2毒素(T-2),由各种镰刀菌产生的A型单霉菌毒素,进入人体后会破坏DNA/RNA和蛋白质的合成,导致各种组织/器官的病理状况,并对人类和动物健康构成重大威胁。然而,其毒性的潜在机制仍不清楚.为了了解T-2如何影响动物的繁殖,我们利用原代猪卵巢颗粒细胞(pGCs)作为体外载体,构建了用于分析细胞形态和RNA测序(RNA-seq)的浓度模型.我们的发现表明T-2可以影响pGC的形态,诱导细胞周期停滞,并以剂量依赖性方式促进细胞凋亡。RNA-seq分析结果表明,共有8216个基因在T-2处理后表现出显著的差异表达(DEG),其中4812被观察到下调,3404被上调。T-2毒素处理pGC后的DEGs对许多代谢途径有显著影响,如PI3K-Akt,拉斯,MAPK,和细胞凋亡,这反过来又改变了重要的生理过程。基因集富集分析(GSEA)表明,T-2有害作用的差异可能是由细胞过程和负责类固醇代谢的途径的不同控制引起的。这些结果提供了有关T-2对母猪生殖毒性作用机制的进一步见解,增强我们对T-2生殖毒理学效应的理解,为正确预防T-2引起的生殖毒性奠定了理论基础。