Impact of vincristine treatment on the mouse ovary and the potential protective effect of dichloroacetate

The increase in survival rates among women with cancer has shifted focus toward fertility preservation. This study investigates the effects of vincristine, a chemotherapy alkaloid, on ovarian function and the potential protective role of dichloroacetic acid (DCA). Adult female mice were divided into four groups receiving vincristine, DCA or both and control. Short- and long-term effects were assessed through histological, immunohistochemical, and functional analyses.Vincristine disrupted estrous cycles, reduced the number of growing follicles, and increased follicular atresia, although the primordial follicle pool remained unaffected. An increase in the activation of primordial follicles and a decrease in AMH signaling were also observed. Long-term outcomes included reduced ovulation and alterations in oocyte diameter and meiotic spindle length. Exposure to both drugs did not fully prevent follicular damage, but it reduced ovarian fibrosis and normalized meiotic spindle morphology.These findings suggest that vincristine, though considered to have low gonadotoxicity, may negatively impact oocyte quality. DCA exhibited a dual role: exacerbating some follicular alterations while improving aspects of oocyte maturation and reducing tissue fibrosis. This highlights the importance of evaluating combined therapies to mitigate adverse reproductive effects in female cancer patients.