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Title: Investigating mechanisms of premature ovarian insufficiency using a mouse model
Author: Sheikh, Sairah
ISNI:       0000 0004 7430 5659
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Premature ovarian insufficiency (POI) occurs in 1% of reproductive-age women. The ovarian manifestation ranges from the presence of a variable population of follicles (follicular) to the absence of follicles (afollicular), and in the majority of cases the cause is unknown. The Double Mutant (DM) mouse model of follicular POI, arises from the oocyte-specific deletion of Mgat1 and C1galt1 required for the generation of Oand N-glycans respectively. DM females are subfertile at 6-weeks, infertile by 9-weeks and undergo POI by 3-months of age and exhibit increasing numbers of primary follicles and a depletion of follicles at the later stages. This is accompanied by elevated gonadotropins and decreased sex steroids, which is characteristic of POI in women. In this thesis, characterisation of follicle development reveals multiple defects at various stages of development including the presence of abnormally large primary follicles resulting a block in follicle development, and luteinisation of unruptured preovulatory follicles resulting in anovulation and infertility. Analysis of in vitro follicle development demonstrated that follicles retain the potential to develop indicating that intra-ovarian factors may be playing a role in the follicle dysfunction. Finally, reaggregated ovaries demonstrate that although DM germ cells retain the potential to develop follicles, DM somatic cells are imprinted with the POI phenotype. These findings highlight new avenues for investigation to further elucidate the mechanisms underpinning POI as well as targets for treatment.
Supervisor: Williams, Suzannah Alice Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available