Li Zongshuai, Ma Tian, Liu Yali, Liu Wanruo, Zhao Xingxu, Zhang Gaiping, Wang Jianlin, Zhang Yong
College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China.
State Key Laboratory of Grassland Agro Ecosystems, Lanzhou University, Lanzhou 730020, China.
Antioxidants (Basel). 2024 Jun 20;13(6):752. doi: 10.3390/antiox13060752.
Zearalenone (ZEN) is a common fungal toxin with reproductive toxicity in various grains. It poses a serious threat to ovine and other animal husbandry industries, as well as human reproductive health. Therefore, investigating the mechanism of toxicity and screening antagonistic drugs are of great importance. In this study, based on the natural compound library and previous Smart-seq2 results, antioxidant and anti-apoptotic drugs were selected for screening as potential antagonistic drugs. Three natural plant compounds (oxysophoridine, rutin, and phellodendrine) were screened for their ability to counteract the reproductive toxicity of ZEN on ovine oocytes in vitro using quantitative polymerase chain reaction (qPCR) and reactive oxygen species detection. The compounds exhibited varying pharmacological effects, notably impacting the expression of antioxidant (, , and ), autophagic (, , and ), and apoptotic (, , and ) genes. Oxysophoridine promoted , , , and expression, while inhibiting and expression. Rutin promoted and expression, and inhibited and expression. Phellodendrine promoted and expression, and inhibited expression. However, all compounds promoted the expression of genes related to cell cycle, spindle checkpoint, oocyte maturation, and cumulus expansion factors. Although the three drugs had different regulatory mechanisms in enhancing antioxidant capacity, enhancing autophagy, and inhibiting cell apoptosis, they all maintained a stable intracellular environment and a normal cell cycle, promoted oocyte maturation and release of cumulus expansion factors, and, ultimately, counteracted ZEN reproductive toxicity to promote the in vitro maturation of ovine oocytes. This study identified three drugs that antagonize the reproductive toxicity of ZEN on ovine oocytes, and compared their mechanisms of action, providing data support and a theoretical basis for their subsequent application in the ovine breeding industry, reducing losses in the breeding industry, screening of ZEN reproductive toxicity antagonists and various toxin antagonists, improving the study of ZEN reproductive toxicity mechanisms, and even protection of human reproductive health.
玉米赤霉烯酮（ZEN）是一种常见的真菌毒素，对各种谷物具有生殖毒性。它对绵羊和其他畜牧业以及人类生殖健康构成严重威胁。因此，研究其毒性机制并筛选拮抗药物具有重要意义。在本研究中，基于天然化合物库和先前的Smart-seq2结果，选择抗氧化和抗凋亡药物作为潜在的拮抗药物进行筛选。使用定量聚合酶链反应（qPCR）和活性氧检测，筛选了三种天然植物化合物（氧化苦参碱、芦丁和黄柏碱）在体外对抗ZEN对绵羊卵母细胞生殖毒性的能力。这些化合物表现出不同的药理作用，显著影响抗氧化（、和）、自噬（、和）和凋亡（、和）基因的表达。氧化苦参碱促进、、和的表达，同时抑制和的表达。芦丁促进和的表达，并抑制和的表达。黄柏碱促进和的表达，并抑制的表达。然而，所有化合物均促进与细胞周期、纺锤体检查点、卵母细胞成熟和卵丘扩展因子相关基因的表达。尽管这三种药物在增强抗氧化能力、增强自噬和抑制细胞凋亡方面具有不同的调节机制，但它们都维持了稳定的细胞内环境和正常的细胞周期，促进了卵母细胞成熟和卵丘扩展因子的释放，最终抵消了ZEN的生殖毒性，促进了绵羊卵母细胞的体外成熟。本研究鉴定了三种拮抗ZEN对绵羊卵母细胞生殖毒性的药物，并比较了它们的作用机制，为其随后在绵羊育种行业中的应用、减少育种行业损失、筛选ZEN生殖毒性拮抗剂和各种毒素拮抗剂、完善ZEN生殖毒性机制研究乃至保护人类生殖健康提供了数据支持和理论依据。
