化疗对女性癌症患者的生育能力产生了严重的副作用，积累的证据表明这与卵母细胞质量的损害有关，但其潜在机制尚不清楚。我们先前报道了阿霉素（DXR）暴露可破坏体外培养的小鼠卵母细胞的减数分裂成熟。在本研究中，我们发现DXR暴露的卵母细胞中SIRT1表达显著降低。接下来，我们发现通过白藜芦醇增加SIRT1表达可部分缓解DXR暴露对卵母细胞成熟的影响，而SIRT1抑制则逆转了这种效应。此外，我们揭示通过降低ROS水平、增加抗氧化酶MnSOD表达以及防止纺锤体和染色体组织的增加SIRT1表达，减轻了DXR引起的卵母细胞损伤，并降低了非整倍体率。重要的是，通过体外受精和胚胎移植试验，我们证明增加SIRT1表达显著提高了卵母细胞的受精能力和早期胚胎的发育能力。总之，我们的数据揭示了SIRT1降低代表了介导DXR暴露对卵母细胞质量影响的机制之一。版权所有 © 2023. 由Elsevier Inc.出版。

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 inhibition. 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 fertilization 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.Copyright © 2023. Published by Elsevier Inc.