Managing the negative regulation of Sirtuins in a murine model of premature ovarian failure: focusing on the key roles of antioxidants

在小鼠卵巢早衰模型中调控Sirtuins的负调控:聚焦抗氧化剂的关键作用

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Abstract

One of the most common side effects of chemotherapy is premature ovarian failure (POF) in women younger than 40. POF is linked to higher levels of gonadotropin hormones, lower levels of estradiol, and increased apoptosis and follicular atresia, all of which lower the quality of fertility and eventually make women unable to have children. There have been more and more reports since 1981 of different treatments that can protect against ovarian damage caused by chemotherapy. However, it is still challenging to find effective fertility-preserving measures for treating POF. Many of the newly proposed or developing chemotherapy treatments and radiotherapy-induced premature ovarian failure have shown limited efficacy or are associated with side effects, and their ability to fully restore ovarian function remains uncertain. However, the use of antioxidants to treat premature ovarian failure is a more effective method with fewer side effects than the recommended treatment methods. Antioxidants reduce symptoms of premature ovarian failure by affecting histone-modifying genes, especially the Sirtuin family, which function as redox environment sensors in granulosa cells and regulate the expression of downstream genes such as FOXO3a, P53, NF-κB, NRF2, and PGC-1a. This study aims to investigate how different treatments, especially antioxidants, can reactivate Sirtuin family genes to help with premature ovarian failure. It is shown that antioxidants, by increasing the expression levels of Sirtuin family genes, have the most significant impact on improving ovarian function in premature ovarian failure induced by multiple chemotherapy drugs.

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