Defects in Mitochondria Impacting Primate Oocyte Quality

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DESCRIPTION (provided by applicant): The overall goal of this study is to examine the functional significance of different mitochondrial characteristics in oocytes as markers or predictors of oocyte health, using the rhesus monkey as the most appropriate experimental model for humans. 3 approaches will be used: (i) assessment of mitochondrial localization profiles in oocytes before, during and after fertilization in vitro using multiphoton microscopy as a non-invasive analytical tool that provides 4-dimensional (4D) information; (ii) determining the functional activity of mitochondria in oocytes and embryos by measuring ATP levels at different stages of development; and (iii) evaluation of mitochondrial mutations in oocytes from humans and oocytes and embryos from young and old monkeys, as well as the evaluation of somatic mtDNA mutations in tissues and cells as a baseline marker for reproductive senescence. The study will determine the extent to which all 3 of these measures of mitochondrial characteristics are related to 1 another, and to embryo development subsequent to fertilization in vitro, in rhesus monkeys. If good correlations are found, this will indicate that the localization profiles and activity of mitochondria typical of developmentally incompetent oocytes represent a pathological condition. Thus, the "normal" localization profiles could be used as a non-invasive marker or predictor of oocyte competence so that only the most viable embryos are selected for embryo transfer. This information could then be evaluated in other clinical studies for application to human oocytes and embryos. This study will also determine if mtDNA defects are manifested as disturbed mitochondrial localization profiles, altered mitochondrial activity, and/or compromised oocyte developmental competence in rhesus monkeys. Information gained in this study will also improve our understanding of the role of mitochondria in primate oocyte and embryo biology, and in the progressive loss of female reproductive capacity with age.