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Abstract

In this thesis, I present four scientific projects that I lead or co-lead during my thesis, each interrogating different aspects of regulation within the female reproductive tract. The first project addresses critical gaps in our understanding of oocyte and granulosa cell interactions within cumulus-oocyte complexes (COCs) in the context of superovulation and ageing. I adapted developmental biology techniques to enable precise comparisons between individually tracked oocyte-granulosa cell pairs and naturally aged COCs. Additionally, I designed a prospective mouse IVF model to non- invasively predict embryo development trajectory using granulosa cell transcriptomes, addressing limitations of retrospective studies. The second project explores the evolutionary transcriptional divergence of oocytes across different mouse species, contributing to our understanding of oocyte evolution - a field predominantly focused on male gametes. Preliminary results suggest nuanced patterns of transcriptional divergence among species. In the third project, I contributed experimentally to a larger scientific project that investigates of the role of fibroblasts in shaping inflammation and extracellular matrix remodelling in the female reproductive tract during ageing. The results emphasize the contribution of fibroblasts to age-related fibrosis and chronic tissue inflammation. Finally, the last project involved collecting extensive datasets of mouse single cell RNA sequencing and spatial transcriptomics data to provide insights into female reproductive tract ageing after repeated hormonal stimulations, complemented by additional experiments in mouse and human. This research project will have significant implications for understanding the long-term effects of hormonal stimulation on reproductive tissue health and the broader mechanisms of reproductive ageing.