(149) Understanding the Relationship Between Oocyte Mitochondrial Aging and Oocyte Aneuploidy

Sydney Cohen^1,2, Karolina Kravarikova^1,2, Kéryanne Gagnon¹, Valeriy Kutsyna¹, Greg FitzHarris^1,3

1. Centre de Recherche du CHUM, Montréal, QC, Canada

2. Department of Molecular Biology, Université de Montréal, Montréal, QC, Canada

3. Department of Pathology and Cell Biology, Université de Montréal, Montréal, QC, Canada

Abstract Text:

Female fertility declines in the mid-thirties due to a decline in oocyte quality, with an increasing proportion of aneuploid oocytes that, when fertilized, become embryos that are mostly incompatible with development. Importantly, there are two types of oocyte aneuploidy: nondisjunction and premature separation of sister chromatids. Premature sister separation is the major type of aneuploidy that occurs with age. Separately, it is also widely accepted that aging causes a progressive dysfunction of oocyte mitochondria, and it has been suggested that oocyte mitochondrial dysfunction may be the cause of age-related oocyte aneuploidy. Pharmacological treatments have been developed capable of preventing these oocyte mitochondrial-level changes in vitro, raising hopes of prolonging female fertility. Importantly, however, whether or not altered mitochondrial function is a direct cause of aneuploidy is unclear. Therefore, to investigate whether oocyte aneuploidy is downstream of oocyte mitochondrial dysfunction, or whether the two defects arise separately, we have constructed a detailed time-course of the development of oocyte aneuploidy in CD1 mice. We confirm that aneuploidy begins around 9 months of age and that most aneuploidy is of the premature sister separation subtype. However, disrupting mitochondrial function in young oocytes did not induce premature separation of sister chromatids, but rather induced some nondisjunction. Conversely, to investigate whether oocyte aneuploidy might rather be upstream of oocyte mitochondrial dysfunction, we induced oocyte aneuploidy in young oocytes and found that mitochondrial function was not changed. Furthermore, there was no difference in cytoplasmic flow between euploid and aneuploid eggs. Our data so far suggest that rather than being inter-dependent, aneuploidy and mitochondrial dysfunction are more likely mechanistically separate elements of oocyte aging. Our data have profound implications for several current and proposed fertility treatments.