Oocyte metabolism – a potential link between mare conditions and impaired fertility
Date
2023
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Abstract
Maternal advanced aging and obesity are known for negatively affecting reproductive outcomes by directly impacting the oocyte and the follicular environment, where the oocyte develops and matures. Success of early embryonic development relies on appropriate ability of the oocyte to produce energy. Whether maternal conditions of the mare impact oocyte metabolic function had not been previously determined. In the studies described throughout this dissertation, novel microsensors were utilized to quantify aerobic and anaerobic metabolism of single equine oocytes. Additional and complementing end points were obtained through high- resolution respirometry of granulosa cells and metabolomic profiling of oocytes and cumulus cells. The overarching hypothesis of this dissertation is that mare conditions known to impair fertility, namely advanced age and obesity, affect oocyte metabolism, ultimately impairing oocyte developmental potential. It was additionally hypothesized that dietary supplementation to old or obese mares would reach and affect the ovarian follicular environment and the oocyte, improving its metabolic function and quality. To test these hypotheses, a series of three projects were conducted to: 1) Investigate effects of mare advanced aging on oocyte metabolism; 2) Determine the potential of diet supplementation to old mares to improve oocyte metabolism; 3) Investigate effects of mare obesity on oocyte metabolism and the potential of diet supplementation on normalizing metabolic alterations. Findings from these projects revealed that mare advanced aging impairs oocyte aerobic and anaerobic metabolic function, contributing to limited embryonic metabolism and development after intracytoplasmic sperm injection (ICSI). Short-term dietary supplementation to old mares with feed additives, specifically formulated to improve mitochondrial metabolism and overall equine health, was able to improve mitochondrial metabolism of granulosa cells and oocytes, promoting greater embryonic rates after ICSI in comparison to a control grain supplementation. Additionally, the findings here reported demonstrate that mare obesity promotes several alterations in the ovarian follicle, including excess of reactive oxygen species production by granulosa cells, lipid accumulation in cumulus cells and oocytes, and excessive oocyte aerobic and anaerobic metabolism. Dietary supplementation to obese mares with similar feed components mitigated many of the obesity-associated follicular changes, likely contributing to oocyte quality. Collectively, these novel discoveries contribute to knowledge and understanding of the direct effects of maternal conditions of the mare on the ovarian follicle and oocyte, elucidating cellular mechanisms by which advanced aging and obesity disturb fertility. Furthermore, these findings reveal the benefits of dietary interventions in improving oocyte metabolism and quality. Dietary supplementation represents a non-invasive and feasible approach to tackle female subfertility. Assuredly the results presented throughout this dissertation will contribute to the equine reproduction industry, with potential to have a translational impact on the human fertility industry, by not only elucidating direct effects of maternal conditions on oocyte metabolism, but also by providing a practical method for rescuing it in vivo.