Discovery of biomarkers and mechanisms of chemotherapy-induced ovarian damage and fertility preservation

1% of women of reproductive age are diagnosed with cancer, with at least 80% surviving after treatment. The increasing survival rates among young cancer patients raise concerns about whether oncology treatments, like gonadotoxic chemotherapy, has induced premature ovarian damage and subsequent infertility. Currently, clinically established fertility preservation methods include freezing of oocytes, embryos, and ovarian tissue. These methods are still facing limitations, including compromised fertility outcome later in life, not feasible in certain clinical circumstances, having side effects, and not maintaining the endocrine function of ovaries. Thus, alternative fertility preservation options with higher efficiency and safety, having wider application and being less invasive are necessary. The current project investigates the mechanisms of cyclophosphamide, one of the most gonadotoxic chemotherapies, induced ovarian damage, looking for biomarkers and mechanisms for tissue damage. Based on this knowledge, we also look for molecules that could block the signaling pathways triggering the tissue damage and help to avoid the cyclophosphamide-caused ovarian toxicity. Moreover, we will look for the therapies that reduce or even prevent the dramatic follicle loss in the grafts of transplanted mice and human ovary tissue in mice model. In conclusion, our project aims to identify prognostic and diagnostic biomarkers for personalized fertility preservation tailored to young female cancer patients who require treatments that damage the ovaries and affect fertility. Additionally, we are exploring novel pharmacological methods to prevent cyclophosphamide- and transplantation-induced rapid follicular loss in ovarian tissue and to maintain the hormonal function of ovaries. Our goal is to develop strategies that not only preserve fertility but also enhance the overall quality of life for these patients by mitigating the adverse effects of cancer treatments on reproductive health.