Molecular Mechanisms of Parturition

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DESCRIPTION (provided by applicant): Parturition, the process of giving birth, is an essential biological function for which the molecular mechanisms are poorly understood. Each year, some 4.5 million severely premature infants are born worldwide due to the failure of normal parturition, and complications associated with delivery in post-term pregnancies cause innumerable problems in both mother and child. Despite extensive studies examining parturition in the human and other species, the sequence of events that initiate and terminate this process remains unclear. The proposed studies will use a parturition defective mouse model to define molecular events that accompany initiation and progression of labor. This model has a targeted mutation that disrupts the steroid 5alpha reductase gene (Steroid 5alpha-reductase type 1 knockout: 5alphaR1KO). The 5alphaR1KO mice have a defect in cervical ripening. Physiological and molecular studies will be undertaken to dissect the steps leading to cervical remodeling during gestation in wild type and 5alphaR1KO females. Studies will be initiated to define the role of new genes in cervical ripening identified by cDNA micro-array gene chip analysis. The 5alphaR1 gene is expressed in a tissue and temporal specific pattern during pregnancy. Studies to identify the regulatory sequences controlling 5alphaR1 expression in the female reproductive tract will be initiated. The integrated approaches applied in these studies will provide novel molecular insight into the mechanisms controlling parturition in the mouse and establish a genetic framework for long-term studies in human parturition.