Zhao Zhifang, Yao Jibin, Guo Zhong, Song Lei, Ma Jianxiu, Song Yihang, Ma Yanqing, Zhao Jin
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730030, China.
Medical College, Northwest Minzu University, Lanzhou, China.
Biol Trace Elem Res. 2025 Jun 19. doi: 10.1007/s12011-025-04707-w.
Environmental pollutants, such as zearalenone (ZEA), a mycotoxin from Fusarium graminearum that contaminates cereal crops and animal feed, significantly threaten reproductive health. The main toxicity mechanism of ZEA involves triggering oxidative stress and apoptosis. Zinc (Zn), a critical antioxidant for reproductive health, may counteract ZEA toxicity, but its mechanism of action remains unclear. The objective of the study was to investigate the alleviating effects of Zn supplementation against ZEA-induced testicular toxicity. We combined network toxicology and animal experiments to evaluate Zn's efficacy. Male Kunming mice were divided into Control, ZEA (2 mg/kg), Zn (20 mg/kg) and ZEA + Zn (10/20/40 mg/kg) groups and treated for 28 days. The results revealed that ZEA exhibited marked reductions in sperm quality, accompanied by structural testicular injury to the testis. ZEA diminishes the activity of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), while simultaneously increasing the levels of malondialdehyde (MDA), which results in oxidative stress. ZEA down-regulates serum levels of testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and impairs steroidogenesis. Significant elevations in ROS levels and apoptotic protein expression were observed in the testicular tissue of the ZEA group. ZEA significantly decreased both the mRNA and protein expression levels of Sirt3 and Foxo3, as well as their immunofluorescence intensity. Zn significantly increased sperm quality, improved testicular morphology, increased Sirt3 and Foxo3 levels, reduced ROS, normalized antioxidant capacity, improved apoptosis, and restored serum hormone levels. These findings emphasize the reproductive risks associated with ZEA, while also highlighting Zn as a possible candidate for developing alleviating effects against mycotoxin-induced reproductive toxicity.
环境污染物，如玉米赤霉烯酮（ZEA），一种来自禾谷镰刀菌的霉菌毒素，可污染谷物作物和动物饲料，对生殖健康构成重大威胁。ZEA的主要毒性机制包括引发氧化应激和细胞凋亡。锌（Zn）是生殖健康的关键抗氧化剂，可能抵消ZEA的毒性，但其作用机制尚不清楚。本研究的目的是探讨补充锌对ZEA诱导的睾丸毒性的缓解作用。我们结合网络毒理学和动物实验来评估锌的功效。将雄性昆明小鼠分为对照组、ZEA（2mg/kg）组、Zn（20mg/kg）组和ZEA+Zn（10/20/40mg/kg）组，并进行28天的治疗。结果显示，ZEA导致精子质量显著下降，并伴有睾丸结构损伤。ZEA降低了抗氧化酶超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性，同时增加了丙二醛（MDA）的水平，从而导致氧化应激。ZEA下调血清睾酮（T）、促卵泡激素（FSH）、黄体生成素（LH）水平，并损害类固醇生成。在ZEA组的睾丸组织中观察到活性氧水平和凋亡蛋白表达显著升高。ZEA显著降低了Sirt3和Foxo3的mRNA和蛋白表达水平，以及它们的免疫荧光强度。锌显著提高了精子质量，改善了睾丸形态，增加了Sirt3和Foxo3水平，降低了活性氧，恢复了抗氧化能力，改善了细胞凋亡，并恢复了血清激素水平。这些发现强调了与ZEA相关的生殖风险，同时也突出了锌作为一种可能对抗霉菌毒素诱导的生殖毒性的缓解剂的候选地位。
