Tumor-derived oxidative stress triggers ovarian follicle loss in breast cancer.

Breast cancer is a common indication for ovarian cryopreservation. However, whether the grafting ovarian tissue meets functional requirements, as well as the need for additional interventions remains unclear. The current study demonstrates abnormal serum hormones in breast cancer in humans and breast cancer cell line-derived tumor-bearing mice, and for the first time show tumor induced loss of primordial and growing follicles and the number of follicles being lost to either growth or atresia. A gene signature of tumor-bearing mice demonstrates the disturbed regulatory network of steroidogenesis which links to mitochondria dysfunction in oocytes and granulosa cells via the PI3K signaling pathway. Notably, increased reactive oxygen species (ROS) is identified in serum and ovarian tissues in tumor-bearing mice. Further, supplementation with vitamin C promotes follicular quiescence, repairing tumor-induced follicle loss via inactivation of the PI3K-Akt-mTOR pathway, indicating that antioxidants should be a potential fertility therapy to achieve more numbers of healthy follicles ready for ovarian cryopreservation.