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. The long-term goals of this research proposal are to enhance our understanding of the processes that control the initiation and progression of parturition, specifically the events that occur in the cervix to facilitate softening and ripening. These studies will lay the groundwork for future genetic studies aimed at identifying gene polymorphisms/mutations that predispose women to cervical incompetence or preterm birth as well as for the identification of biochemical markers for positive prediction of preterm labor. Studies in Specific Aim 1 will focus on the identification of sequences in the 5a-reductase type 1 gene that orchestrate the unique cell and temporal specific expression of this gene in pregnancy and parturition. Studies outlined in Specific Aim 2 will enhance our understanding of transcriptional, translational and structural changes that mediate cervical softening, a process that is distinct from cervical ripening. The studies outlined in Specific Aim 3 will clarify our understanding of the role inflammatory processes play in initiation of normal cervical ripening by identifying cells recruited to the cervix and the timing of activation of these cells. Studies in Specific Aim 4 will enhance our understanding of the role cervical epithelial play in facilitating cervical remodeling at parturition, specifically the regulation of paracellular transport by tight junction proteins and epithelial differentiation. Insights gained from this research will further our understanding of the parturition process and lead to therapies for the prevention of preterm birth which affects up to 14% of pregnancies in North America. Premature infants born before 37 weeks gestation are at a higher risk of infant mortality, breathing complications and suffering lifelong medical complications thus our studies aimed at preventing preterm labor are of significant relevance to public health.