Polycystic ovarian syndrome (PCOS) is a multi-factorial infertility disorder whose etiology and pathogenesis is not completely understood. Although there is an association between dysregulation of mitochondrial fission and fusion to cell death (apoptotic and autophagic) and the pathogenesis of various diseases, this had not been reported in the context of granulosa cell death, follicular growth arrest and PCOS. Follicle-stimulating hormone (FSH), a granulosa cell survival factor, is used during gonadotropin therapy to assist in follicular maturation and ovulation in women with PCOS. Whether FSH can modulate the possible dysregulation of granulosa cell mitochondrial dynamics and cell death in PCOS had not been elucidated. Chemerin is an adipokine that has been associated with PCOS and granulosa cell apoptosis in follicle cultures. Its role in cell death (apoptotic and autophagic) of primary granulosa cells had not been confirmed.
In this thesis, we investigated the dysregulation of granulosa cell mitochondrial dynamics in PCOS pathogenesis by using an androgenized rat model, and its modulation by exogenous gonadotropin. The mechanisms involved in gonadotropic regulation were investigated using primary granulosa cells. Our data suggest that increased mitochondrial fission leads to early antral granulosa cell death, follicular growth arrest and anovulation in women with PCOS. FSH can regulate the phosphorylation of mitochondrial fission protein Drp1, which may lead to its suppression of mitochondrial fission and apoptosis in PCOS. Finally, chemerin had no effect on cell death in granulosa cell cultures. These findings provide a greater understanding of the processes involved in PCOS pathogenesis and the regulatory role of FSH in granulosa cells, laying the foundation for future study into the development of potential biomarkers and new treatment strategies.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/35572 |
| Date | January 2016 |
| Creators | Mazier, Hannah |
| Contributors | Tsang, Benjamin |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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