SIRT1 reduction contributes to doxorubicin-induced oxidative stress and meiotic failure in mouse

文献类型： 外文期刊

第一作者： Han, Jun

作者： Han, Jun;Han, Jun;Wang, Shuo;Wang, Huarong;Zhang, Tuo;Yang, Ye;Zhao, Ting;Chen, Ziqi;Xia, Guoliang;Wang, Chao;Xia, Guoliang

作者机构：

关键词： Doxorubicin; SIRT1; Oocyte; Oxidative stress; Meiotic maturation

期刊名称：TOXICOLOGY AND APPLIED PHARMACOLOGY （ 影响因子：3.8； 五年影响因子：4.0 ）

ISSN： 0041-008X

年卷期： 2023 年 476 卷

页码：

收录情况： SCI

摘要： Impaired fertility is the major side effect of chemotherapy for female cancer patients, accumulated evidence indicates this is associated with damage on oocyte quality, but the underlying mechanisms remain unclear. Previously we reported that doxorubicin (DXR) exposure, one of the most widely used chemotherapy drugs, disrupted mouse oocyte meiotic maturation in vitro. In the current study, we identified that SIRT1 expression was remarkably reduced in DXR exposure oocytes. Next, we found that increasing SIRT1 expression by resveratrol partially alleviated the effects of DXR exposure on oocyte maturation, which was counteracted by SIRT1 inhi-bition. Furthermore, we revealed that increasing SIRT1 expression mitigated DXR induced oocyte damage through reducing ROS levels, increasing antioxidant enzyme MnSOD expression, and preventing spindle and chromosome disorganization, lowering the incidence of aneuploidy. Importantly, by performing in vitro fertil-ization and embryo transfer assays, we demonstrated that increasing SIRT1 expression significantly improved the fertilization ability, developmental competence of oocytes and early embryos. In summary, our data uncover that SIRT1 reduction represents one mechanism that mediates the effects of DXR exposure on oocyte quality.

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