T-2 toxin exposure induces ovarian damage in sows: lncRNA CUFF.253988.1 promotes cell apoptosis by inhibiting the SIRT3/ PGC1α pathway

文献类型： 外文期刊

第一作者： Yang, Chenglin

作者： Yang, Chenglin;Fan, Hui;Wu, You;Wang, Yongkang;Wu, Aoao;Li, Yuanyuan;Yuan, Zhihang;Yi, Jine;Wu, Jing;Yang, Chenglin;Fan, Hui;Wu, You;Wang, Yongkang;Wu, Aoao;Li, Yuanyuan;Yuan, Zhihang;Yi, Jine;Yin, Deming;Wu, Jing;Wu, Jing;Liang, Zengenni;Liang, Zengenni

作者机构：

关键词： T-2 toxin; LncRNA CUFF.253988.1; Mitochondrial; SIRT3/PGC-1 alpha pathway

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.2； 五年影响因子：6.3 ）

ISSN： 0147-6513

年卷期： 2024 年 283 卷

页码：

收录情况： SCI

摘要： T-2 toxin, a mycotoxin found in foods and feeds, poses a threat to female reproductive health in both humans and animals. LncRNA CUFF.253988.1 (CUFF.253988.1), highly expressed in pigs, has an undisclosed regulatory role. This study aimed to establish a model of T-2 toxin-induced ovarian injury in sows, both in vivo and in vitro, and to explore the regulatory role and potential mechanisms of CUFF.253988.1. The results showed that feeding T-2 toxin-contaminated feed (1 mg/kg) induced ovarian follicle atresia and mitochondrial structural damage, accompanied by a significant upregulation of CUFF.253988.1 expression in the ovaries. Additionally, T-2 toxin inhibited the SIRT3/PGC1-alpha pathway associated with mitochondrial function. Moreover, T-2 toxin induced cell apoptosis by upregulating the expression of Cyt c , Bax, cleaved-caspase-9, and cleaved-caspase-3 proteins. In T-2 toxin-induced injury to the ovarian granulosa AVG-16 cells at concentrations of 10, 40 and 160 nM, not only were the previously mentioned effects observed, but also a decrease in mitochondrial membrane potential, ATP content, and an elevation in ROS levels. However, downregulating CUFF.253988.1 reversed T-2 toxin's inhibition of the SIRT3/PGC1-alpha pathway, alleviating mitochondrial dysfunction and reducing cell apoptosis. Notably, this may be attributed to the inhibition of T-2 toxin-induced enrichment of CUFF.253988.1 in mitochondria. In conclusion, CUFF.253988.1 plays a pivotal role in T-2 toxin-induced ovarian damage, operating through the inhibition of the SIRT3/PGC1-alpha pathway and promotion of cell apoptosis.

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