College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Harbin 150030, PR China.
Sci Total Environ. 2024 Dec 1;954:176432. doi: 10.1016/j.scitotenv.2024.176432. Epub 2024 Sep 21.
Deoxynivalenol (DON) is a toxic secondary metabolite produced by Fusarium spp. It is widely distributed among various cereals and has attracted much attention as a potential health threat to humans and domestic animals. However, the effects of DON on the reproductive systems of mammals are still ambiguous. In this study, the toxic effects of DON in the male reproduction of mice were investigated. The results showed that DON caused the shedding of sperm cells at all testis levels and the presence of inflammatory cells in the testicular interstitium. The rate of living sperm was significantly reduced, and the rate of sperm deformity was increased after DON exposure. The DON exposure resulted in decreased levels of testosterone (T) and increased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the serum. Measurements of oxidative stress markers showed that DON induced oxidative stress in mice testis. Meanwhile, DON triggered the assembly of NLRP3-ASC-Caspase-1 inflammatory complex and pyroptosis in both mice testis and TM3 cells, further causing the activation of GSDMD, promoting the leakage of inflammatory cytokines, including IL-1β and IL-18. Notably, the inhibition of oxidative stress was found to protect pyroptosis in TM3 cells exposed to DON. We identified a novel mechanism of reproductive damage induced by DON, demonstrating the activation of the canonical Caspase-1-dependent pyroptosis pathway and clarifying the protection of antioxidation against pyroptosis damage. Our discovery provided support for the risk assessment of DON and target exploration for clinical treatment related to pyroptosis.
脱氧雪腐镰刀菌烯醇（DON）是镰刀菌属产生的一种有毒次生代谢物。它广泛分布于各种谷物中，作为人类和家畜潜在的健康威胁而受到广泛关注。然而，DON 对哺乳动物生殖系统的影响仍不清楚。在本研究中，研究了 DON 对雄性小鼠生殖系统的毒性作用。结果表明，DON 导致所有睾丸水平的精子细胞脱落和睾丸间质中炎症细胞的存在。活精子率显著降低，暴露于 DON 后精子畸形率增加。DON 暴露导致血清中睾酮（T）水平降低，促卵泡激素（FSH）和黄体生成素（LH）水平升高。氧化应激标志物的测量表明，DON 诱导了小鼠睾丸的氧化应激。同时，DON 在小鼠睾丸和 TM3 细胞中引发 NLRP3-ASC-Caspase-1 炎症复合物和细胞焦亡的组装，进一步导致 GSDMD 的激活，促进包括 IL-1β 和 IL-18 在内的炎症细胞因子的渗漏。值得注意的是，发现抑制氧化应激可保护 TM3 细胞暴露于 DON 时的细胞焦亡。我们确定了 DON 诱导生殖损伤的新机制，证明了经典 Caspase-1 依赖性细胞焦亡途径的激活，并阐明了抗氧化作用对细胞焦亡损伤的保护作用。我们的发现为 DON 的风险评估和与细胞焦亡相关的临床治疗靶点的探索提供了支持。
