2. Academic Validation
  3. SIRT1 reduction contributes to doxorubicin-induced oxidative stress and meiotic failure in mouse oocytes

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

  • Toxicol Appl Pharmacol. 2023 Aug 24;116671. doi: 10.1016/j.taap.2023.116671.
Jun Han 1,  Shuo Wang 2,  Huarong Wang 2,  Tuo Zhang 2,  Yang Ye 2,  Ting Zhao 2,  Ziqi Chen 2,  Guoliang Xia 3,  Chao Wang 4
Affiliations

Affiliations

  • 1 Jiangsu Academy of Agricultural Sciences, Nanjing 21000, China; State Key Laboratory of Livestock and Poultry Biotechnology Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 2 State Key Laboratory of Livestock and Poultry Biotechnology Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
  • 3 State Key Laboratory of Livestock and Poultry Biotechnology Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Ningxia University, Ningxia 750021, China.
  • 4 State Key Laboratory of Livestock and Poultry Biotechnology Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China. Electronic address: [email protected].
PMID: 37633598 DOI: 10.1016/j.taap.2023.116671
Abstract

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.

Keywords

Doxorubicin; Meiotic maturation; Oocyte; Oxidative stress; SIRT1.

Figures
Products