玉米赤霉烯酮（ZEN）是一种常见的真菌毒素，在各种谷物中具有生殖毒性。对绵羊等畜牧业构成严重威胁,以及人类的生殖健康。因此,研究毒性机制和筛选拮抗药物具有重要意义。在这项研究中,基于天然化合物库和以前的Smart-seq2结果，选择抗氧化和抗凋亡药物作为潜在拮抗药物进行筛选。三种天然植物化合物（氧化苦参碱，芦丁,使用定量聚合酶链反应（qPCR）和活性氧检测，筛选了黄柏碱）在体外抵抗ZEN对绵羊卵母细胞的生殖毒性的能力。这些化合物表现出不同的药理作用，特别是影响抗氧化剂的表达(GPX，SOD1和SOD2),自噬（ATG3，ULK2和LC3），和凋亡（CAS3，CAS8和CAS9）基因。OxysophoridinepromotedGPX,SOD1、ULK2和LC3表达，同时抑制CAS3和CAS8的表达。芦丁促进SOD2和ATG3的表达，并抑制CAS3和CAS9的表达。黄柏碱促进SOD2和ATG3的表达，并抑制CAS9表达。然而,所有化合物都促进细胞周期相关基因的表达，主轴检查点,卵母细胞成熟,和积云扩展因子。虽然三种药物在增强抗氧化能力方面有不同的调节机制,增强自噬，抑制细胞凋亡，它们都维持了稳定的细胞内环境和正常的细胞周期,促进卵母细胞成熟和卵丘扩张因子的释放，and,最终,对抗ZEN生殖毒性，促进绵羊卵母细胞体外成熟。这项研究确定了三种拮抗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，为其在绵羊养殖业的后续应用提供数据支持和理论依据，减少养殖业的损失，ZEN生殖毒性拮抗剂和各种毒素拮抗剂的筛选，改进ZEN生殖毒性机制的研究，甚至保护人类的生殖健康。
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 (GPX, SOD1, and SOD2), autophagic (ATG3, ULK2, and LC3), and apoptotic (CAS3, CAS8, and CAS9) genes. Oxysophoridine promoted GPX, SOD1, ULK2, and LC3 expression, while inhibiting CAS3 and CAS8 expression. Rutin promoted SOD2 and ATG3 expression, and inhibited CAS3 and CAS9 expression.
Phellodendrine promoted SOD2 and ATG3 expression, and inhibited CAS9 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.
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