Abstract
Doxorubicin (DXR), a widely used chemotherapeutic drug, has adverse effects on female fertility in young cancer patients. However, the underlying mechanisms of doxorubicin exposure on female fertility and how to prevent it have not been well studied yet. Here, mouse oocytes were employed to investigate the issues mentioned above. The results showed that doxorubicin treatment impaired oocyte meiotic maturation by destroying spindle assembly and chromosome arrangement. In addition, doxorubicin caused oxidative stress by increasing reactive oxygen species (ROS) levels. Furthermore, doxorubicin led to severe DNA damage in oocytes, which eventually induced apoptosis through DNA damage-P63-Caspase3 pathway. Conversely, resveratrol (RES) effectively improved oocyte quality by restoring spindle and chromosome configuration, reducing ROS levels and inhibiting apoptosis. In summary, our results indicate that RES can protect oocytes against doxorubicin-induced damage.
Highlights
DXR is a widely used anthracycline antibiotic, which is clinically used in the treatment of various malignant cancers, such as leukemia, lymphomas, breast, ovarian and endometrial cancer [1, 2]
We further demonstrated that DXR caused increased oxidative stress, DNA damage and apoptosis through DNAdamage-P63-Caspase3 pathway in mouse oocytes
Recent studies have demonstrated that RES protects oocytes from chemical agents-induced oxidative stress and apoptosis
Summary
DXR is a widely used anthracycline antibiotic, which is clinically used in the treatment of various malignant cancers, such as leukemia, lymphomas, breast, ovarian and endometrial cancer [1, 2]. Its clinical use is limited by its dose-dependent toxicity in several organs and systems. Previous studies have shown DXR has cardiotoxicity, hepatotoxicity and reproductive toxicity [3, 4]. Premature ovarian failure, and increasing infertility rates are the major problems for young female cancer survivors [5, 6]. The increasing survival rate of young cancer patients leads to more concern about their fertility state, it is important to illuminate the toxic effects and possible mechanisms of chemotherapeutic drugs on related organs and cells
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