In all vertebrates, oocyte development is arrested at the prophase of meiosis I (MI). Oocytes can remain arrested in this state for the entire reproductive lifespan of the organism; in humans as long as forty years. Resumption of meiosis requires activation of maturation promoting factor (MPF), the complex of cyclin B and cyclin dependent kinase-1 (CDK1/p34cdc2). The mechanism of MPF activation in mammals has remained elusive and the inability to mature human oocytes is a major problem for in vitro fertilization (IVF) clinics. We recently demonstrated that oocytes from mice lacking an MPF activator, the Cdc25B phosphatase, fail to resume meiosis after prophase arrest. Mice lacking Cdc25B provide the first genetic model for prophase arrest in mammals and provide a unique reagent with which to dissect the molecular mechanisms regulating mammalian meiosis.
The specific aims of the proposal are designed to answer fundamental questions about the control of meiosis in mammals and provide the scientific foundation for future clinical advances.
The specific aims are designed: i) To determine the subcellular localization of Cdc25B in the maturing oocyte, ii) To define the functional domains of the Cdc25B molecule, iii) To determine whether pathways that regulate Cdc25B activity during mitosis also act during meiosis, and iv) To use the Cdc25B protein as a unique tag to dissect the pathway controlling prophase arrest and meiotic resumption in mammals.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
7R01HD041553-07
Application #
7490315
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Tasca, Richard J
Project Start
2002-06-01
Project End
2008-05-31
Budget Start
2006-06-03
Budget End
2008-05-31
Support Year
7
Fiscal Year
2006
Total Cost
$251,460
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697