A remarkably high rate of failure appears to be an inherent characteristic of human reproduction. The collective worldwide experience with medically-assisted conception demonstrates that a high proportion of the embryos produced by in vitro fertilization are not developmentally viable. An accumulating body of clinical evidence strongly suggests that many of the causes of developmental failure during the preimplantation stages of human embryogenesis originate in the preovulatory oocyte. The overall objective of this research is to examine molecular and cellular characteristics of oogenesis that may influence or determine developmental potential. Specific aspects of metabolism, physiology, cytoplasmic organization, and chromosomal maturation will be analyzed in uninseminated, unfertilized, and in vitro matured mouse and human oocytes by invasive and noninvasive biochemical and microscope techniques. The influence of extrinsic factors on developmental potential will be assessed by analysis of the physical and chemical milieu associated with the maturation of each oocyte. The findings will determine the extent to which differences in cellular metabolism, organization and physiology can be related to fertilization and early embryonic failure in the human. The long- term goal of these studies is to establish clinically acceptable criteria that use noninvasive methods to evaluate the developmental potential of each oocyte available for insemination. While the research involves multifaceted analyses on a variety of materials from both human and mouse subjects, the project is unified by the information the structures are expected to yield. Elucidating specific factors associated with the high rate of failure that occurs in human reproduction both enhances understanding of reproduction in general, and allows for optimization of techniques to improve reproductive success when laboratory assistance is required.
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