Coenzyme Q10 attenuated cyclophosphamide-induced ovarian damage through the upregulation of PCNA and FSHR genes in female mice

Background and Objective: Cyclophosphamide (CTX) has been broadly used in the clinic for the treatment of autoimmune disorders and ovarian cancer. The process of chemotherapy has significant toxicity in the reproductive system as it has detrimental effects on folliculogenesis, leading to irreversible premature ovarian failure (POF). Coenzyme Q10 (CoQ10), has been shown to have positive impacts on the reproductive system due to its antioxidant properties, protecting the cells from free-radical oxidative damage and apoptosis. However, little is known about the possible synergistic effect of CTX and CoQ10 on the expression of genes involved in folliculogenesis, such as proliferation cell nuclear antigen (PCNA) and follicle stimulating hormone receptor (FSHR). Method and Material: A total number of 40 NMRⅠ mice were applied and divided into four groups, including healthy control, CTX, CTX+CoQ10, and coQ10 groups. The effects of CoQ10 on CTX-induced ovarian injury and folliculogenesis were examined by histopathological, qRT-PCR, and western blot analyses. The rate of in vitro fertilization (IVF) and embryo development, as well as the level of reactive oxygen species (ROS) in metaphase Ⅱ (MⅡ) mouse oocyte after PMSG/HCG treatment. Results: Results showed that the treatment with CTX decreased the mRNA and protein expression of PCNA and FSHR, ROS levels, IVF rate, and embryo development whereas the application of CoQ10 administration significantly enhanced histological morphology and decreased the number of atretic follicle in the ovary of CTX-treated mice. Conclusion: In conclusion, it seems that the protective effect of CoQ10 is exerted via the antioxidant properties of this substance on CTX-induced ovarian damage.

Keywords:

Cyclophosphamide , Coenzyme Q10 , Ovary , Gene expression , in vitro fertilization