Vitamin C protects carboplatin-exposed oocytes from meiotic failure

Abstract

CBP (carboplatin) is a second-generation chemotherapeutic drug of platinum compound commonly applied in the treatment of sarcomas and germ cell tumours. Although it is developed to replace cisplatin, which has been proven to have a variety of side effects during cancer treatment, CBP still exhibits a certain degree of toxicity including neurotoxicity, nephrotoxicity, hematotoxicity and myelosuppression. However, the underlying mechanisms regarding how CBP influences the female reproductive system especially oocyte quality have not yet been fully determined. Here, we report that CBP exposure led to the oocyte meiotic defects by impairing the dynamics of the meiotic apparatus, leading to a remarkably aberrant spindle organisation, actin polymerisation and mitochondrial integrity. Additionally, CBP exposure caused compromised sperm binding and fertilisation potential of oocytes by due to an abnormal distribution of cortical granules and its component ovastacin. More importantly, we demonstrated that vitamin C supplementation prevented meiotic failure induced by CBP exposure and inhibited the increase in ROS levels, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate the toxic effects of CBP exposure on oocyte development and provide a potential effective way to improve the quality of CBP-exposed oocytes in vitro.