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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD031907-04
Application #
2403397
Study Section
Special Emphasis Panel (SRC (04))
Project Start
1994-05-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Van Blerkom, J; Davis, P (2001) Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro. Hum Reprod 16:757-64
Antczak, M; Van Blerkom, J (2000) The vascular character of ovarian follicular granulosa cells: phenotypic and functional evidence for an endothelial-like cell population. Hum Reprod 15:2306-18
Van Blerkom, J (2000) Intrafollicular influences on human oocyte developmental competence: perifollicular vascularity, oocyte metabolism and mitochondrial function. Hum Reprod 15 Suppl 2:173-88
Antczak, M; Van Blerkom, J (1999) Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains. Hum Reprod 14:429-47
Vendrell, F J; Ten, J; De Oliveira, M N et al. (1999) Effect of intracellular Ca2+ chelation with the acetoxymethyl ester-derived form of bis(o-aminophenoxy)ethane-N,N,N,N',N'-tetraacetic acid on meiotic division and chromosomal segregation in mouse oocytes. J Assist Reprod Genet 16:276-82
Van Blerkom, J; Davis, P W (1998) DNA strand breaks and phosphatidylserine redistribution in newly ovulated and cultured mouse and human oocytes: occurrence and relationship to apoptosis. Hum Reprod 13:1317-24
Van Blerkom, J (1998) Epigenetic influences on oocyte developmental competence: perifollicular vascularity and intrafollicular oxygen. J Assist Reprod Genet 15:226-34
Tarin, J J; Cano, A (1998) Distribution of 5-chloromethylfluorescein diacetate staining during meiotic maturation and fertilization in vitro of mouse oocytes. J Reprod Fertil 114:211-8
Van Blerkom, J; Sinclair, J; Davis, P (1998) Mitochondrial transfer between oocytes: potential applications of mitochondrial donation and the issue of heteroplasmy. Hum Reprod 13:2857-68
Antczak, M; Van Blerkom, J (1997) Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo. Mol Hum Reprod 3:1067-86

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