Abstract
Cancer treatment, such as chemotherapy, induces early ovarian follicular depletion and subsequent infertility. In order to protect gametes from the gonadotoxic effects of chemotherapy, several fertility preservation techniques—such as oocyte or embryo cryopreservation with or without ovarian stimulation, or cryopreservation of the ovarian cortex—should be considered. However, these methods may be difficult to perform, and the future use of cryopreserved germ cells remains uncertain. Therefore, improving the methods currently available and developing new strategies to preserve fertility represent major challenges in the area of oncofertility. Animal and ovarian culture models have been used to decipher the effects of different cytotoxic agents on ovarian function and several theories regarding chemotherapy gonadotoxicity have been raised. For example, cytotoxic agents might (i) have a direct detrimental effect on the DNA of primordial follicles constituting the ovarian reserve and induce apoptosis; (ii) induce a massive growth of dormant follicles, which are then destroyed; or (ii) induce vascular ovarian damage. Thanks to improvements in the understanding of the mechanisms involved, a large number of studies have been carried out to develop molecules limiting the negative impact of chemotherapy on the ovaries.
Highlights
In the past few decades, the significant diagnostic and therapeutic progress made in the field of oncology has improved the survival rates of children and young adults
We showed that the ovaries of cyclophosphamide-treated mice were depleted of primordial follicles, whereas the number of primordial and early-growing follicles was similar to that in controls among the ovaries of mice treated with concomitant injections of cyclophosphamide and anti-Müllerian hormone (AMH)
Our results suggested that AMH might inhibit primordial follicle recruitment by preventing cytoplasmic shuttling of FoxO3A induced by cyclophosphamide
Summary
In the past few decades, the significant diagnostic and therapeutic progress made in the field of oncology has improved the survival rates of children and young adults. The application of these methods may be limited by age, pubertal status, disease, and emergency These procedures may be difficult to perform, and the future use of cryopreserved germ cells remains uncertain. It is important to distinguish between the short- and long-term effects of drugs on the ovaries. The impact of drugs on fertility after healing concerns the effects of chemotherapy on the primordial follicular reserve as these treatments may lead to a premature loss and, at worst, primary ovarian insufficiency (POI). Chemotherapeutic agents could exert direct toxicity on primordial follicles, inducing DNA damage and subsequent apoptosis. Increasing knowledge of the possible mechanisms implicated in chemotherapy-induced ovarian damage will facilitate the development of new therapies, called fertoprotective agents [4], aimed at protecting the follicular reserve [5]
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