Title:
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Investigation of the effects of Anti-Müllerian Hormone on preventing Doxorubicin-induced primordial follicle loss
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Survival rates from childhood cancer are improving, however chemotherapy can cause ovarian failure and infertility. Doxorubicin (DXR) is a gonadotoxic chemotherapy agent commonly used in childhood cancers. For pre-pubertal girls, ovarian tissue cryopreservation is the only fertility preservation option, however it is invasive and currently experimental. Therefore, non-invasive options need to be developed. A potential strategy utilizing Anti-Müllerian Hormone (AMH) to inhibit primordial follicle activation exists, but needs to be fully investigated. To determine the effect of AMH on DXR-induced primordial follicle loss in vitro, pre-pubertal mouse ovaries were cultured with AMH, DXR or co-treated with AMH and DXR. To determine the effect of AMH on DXR-induced primordial follicle loss in vivo, pre-pubertal human ovarian tissue was xenotransplanted into adult female immunocompromised mice administered with AMH, DXR or co-treated with AMH and DXR. Mouse and human ovarian tissues were collected after experiments, fixed, embedded, sectioned and stained with Haematoxylin and Eosin. Primordial follicles (in vitro and in vivo studies) and growing follicles (in vivo studies) were counted. In this thesis, we showed that DXR induced primordial follicle loss in pre-pubertal mouse ovarian tissue in vitro, in a dose-dependent manner. Follicular damage caused by DXR was also demonstrated in adult mouse ovaries in vivo but not in human pre-pubertal ovarian tissue xenotransplanted into mice. Although there were trends, there was no significant effect of AMH treatment alone on inhibiting primordial follicle activation in mouse ovarian tissue (in vitro and in vivo) or human ovarian tissue (xenotransplanted into mice). There was also no significant evidence of AMH acting to prevent DXR-induced primordial follicle loss in mouse ovaries. Therefore, more studies are warranted to further investigate the effect of AMH on DXR-induced primordial follicle loss.
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