Oogenesis culminates in the production of viable and developmentally competent ova as a result of an intricate series of metabolic changes in the cumulus-oocyte complex induced by hormones at ovulation. Disturbances in oocyte maturation lead to reproductive failure, manifest as infertility, spontaneous abortion, or birth defects, when errors in chromosome segregation occur during meiosis or when the hormonal requirements for the maturation process are not met. This proposal seeks to define important physiological aspects of oocyte maturation in mammals with respect to protein metabolism, meiotic cell cycle control and somatic cell-gamete interactions using a multidisciplinary approach. The major aims are: (1) To establish how changes in protein metabolism are regulated during meiotic maturation in the mouse oocyte. Translational, and post- translational metabolic processes will be evaluated with respect to meiotic competence acquisition and meiotic resumption/completion. The role of the cytoskeleton in mRNA processing will be analyzed by a combination of biochemical, morphological and micromanipulation procedures. (2) To determine how components of Maturation-Promoting Factor (MPF) mediate meiotic cell cycle progression. The role of centrosomes in activation of the M-phase kinase, localization of p34cdc2/cyclins and morphogenesis of the meiotic spindle will be analyzed using fluorescence digital imaging microscopy and biochemical techniques. (3) To define the physiological basis for information transfer between follicle cells and oocytes. Compositional and functional parameters of junctional contact sites will be analyzed in mouse and cow oocytes during meiotic maturation using vital stain video, fluorescence ratio and confocal imaging light microscopic methods. Information obtained from these studies will help to understand the causes of infertility in women, provide new avenues for improving assisted reproductive technologies, and open new directions for the study of environmentally-based determinants of reproductive failure in mammals.
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