MATERNAL AGING AND MEIOTIC REGULATION IN OOCYTES

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The goal of this research is to examine the effects of maternal aging on the process of meiosis in the human oocyte. Women attempting to reproduce when they are beyond their prime reproductive years often experience an increased incidence of nondisjunction in their oocytes. This represents a significant public health issue since more women are attempting to reproduce at an older age than ever before. The cause of the nondisjunction is due to abnormalities in the process of meiosis that have yet to be identified. We have data from younger (age 20-25) and older women (age 40-45) demonstrating that the meiotic spindle in older women is abnormal with regard to the microtubule matrix and chromosome alignment. This suggests that the regulatory mechanism responsible for meiotic spindle assembly are altered in older women, thus leading to irregular spindles and abnormal chromosome placement. There are large gaps in our knowledge of the different phases of meiosis in the human oocyte particularly with regard to the affects of aging. Our specific goals are threefold: 1) To examine the patterns of chromosome movement during meiosis in living human oocytes from different age groups followed by examination of the expression and placement of regulatory proteins involved in meiotic spindle assembly. 2) Analyze the recruitment of specific cytoplasmic domains that are thought to be involved in meiosis in the human oocyte. 3) Use an aging animal model to examine similar aspects of meiosis during maternal aging. We hypothesize that maternal aging causes temporal and spatial changes in chromosome movement and alteration of specific regulatory elements during the early phases of meiosis. These experiments will provide information on the mechanisms responsible for the nondisjunction that often occurs due to advanced maternal age. Identification of specific molecular events in the oocyte that are affected by age will lead to strategies for the prevention of nondisjunction in older women.