College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China.
Department of Food Science and Engineering, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
Toxins (Basel). 2023 Jul 21;15(7):471. doi: 10.3390/toxins15070471.
Zearalenone (ZEA) and deoxynivalenol (DON) are widely found in various feeds, which harms livestock's reproductive health. Both mitochondria and endoplasmic reticulum (ER) can regulate cell apoptosis. This study aimed to explore the regulatory mechanism of endoplasmic reticulum stress (ERS) on ZEA- combined with DON-induced mitochondrial pathway apoptosis in piglet Sertoli cells (SCs). The results showed that ZEA + DON damaged the ultrastructure of the cells, induced apoptosis, decreased mitochondrial membrane potential, promoted the expression of cytochrome c (CytC), and decreased the cell survival rate. Furthermore, ZEA + DON increased the relative mRNA and protein expression of , , , and , while that of and declined. ZEA + DON was added after pretreatment with 4-phenylbutyric acid (4-PBA). The results showed that 4-PBA could alleviate the toxicity of ZEA + DON toward SCs. Compared with the ZEA + DON group, 4-PBA improved the cell survival rate, decreased the apoptosis rate, inhibited CytC expression, and increased mitochondrial membrane potential, and the damage to the cell ultrastructure was alleviated. Moreover, after pretreatment with 4-PBA, the relative mRNA and protein expression of , , , and were downregulated, while the relative mRNA and protein expression of and were upregulated. It can be concluded that ERS plays an important part in the apoptosis of SCs co-infected with ZEA-DON through the mitochondrial apoptosis pathway, and intervention in this process can provide a new way to alleviate the reproductive toxicity of mycotoxins.
玉米赤霉烯酮（ZEA）和脱氧雪腐镰刀菌烯醇（DON）广泛存在于各种饲料中，危害家畜的生殖健康。线粒体和内质网（ER）均可调控细胞凋亡。本研究旨在探讨内质网应激（ERS）对 ZEA-结合 DON 诱导猪睾丸支持细胞（SCs）线粒体通路凋亡的调控机制。结果表明，ZEA+DON 破坏了细胞的超微结构，诱导细胞凋亡，降低线粒体膜电位，促进细胞色素 c（CytC）表达，降低细胞存活率。此外，ZEA+DON 增加了 、 、 、 和 的相对 mRNA 和蛋白表达，而 、 和 的表达下降。用 4-苯丁酸（4-PBA）预处理后添加 ZEA+DON。结果表明，4-PBA 可减轻 ZEA+DON 对 SCs 的毒性。与 ZEA+DON 组相比，4-PBA 提高了细胞存活率，降低了细胞凋亡率，抑制了 CytC 表达，增加了线粒体膜电位，减轻了细胞超微结构损伤。此外，经 4-PBA 预处理后， 、 、 、 和 的相对 mRNA 和蛋白表达下调，而 、 和 的相对 mRNA 和蛋白表达上调。由此可见，ERS 通过线粒体凋亡途径在 ZEA-DON 共同感染的 SCs 凋亡中发挥重要作用，干预这一过程可为缓解霉菌毒素的生殖毒性提供新途径。
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