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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD043154-08
Application #
7880552
Study Section
Pregnancy and Neonatology Study Section (PN)
Program Officer
Ilekis, John V
Project Start
2002-12-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
8
Fiscal Year
2010
Total Cost
$245,520
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
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Timmons, Brenda C; Reese, Jeff; Socrate, Simona et al. (2014) Prostaglandins are essential for cervical ripening in LPS-mediated preterm birth but not term or antiprogestin-driven preterm ripening. Endocrinology 155:287-98
Mahendroo, Mala (2012) Cervical remodeling in term and preterm birth: insights from an animal model. Reproduction 143:429-38
Holt, Roxane; Timmons, Brenda C; Akgul, Yucel et al. (2011) The molecular mechanisms of cervical ripening differ between term and preterm birth. Endocrinology 152:1036-46
Akins, Meredith L; Luby-Phelps, Katherine; Bank, Ruud A et al. (2011) Cervical softening during pregnancy: regulated changes in collagen cross-linking and composition of matricellular proteins in the mouse. Biol Reprod 84:1053-62
Akins, Meredith L; Luby-Phelps, Katherine; Mahendroo, Mala (2010) Second harmonic generation imaging as a potential tool for staging pregnancy and predicting preterm birth. J Biomed Opt 15:026020
Timmons, Brenda; Akins, Meredith; Mahendroo, Mala (2010) Cervical remodeling during pregnancy and parturition. Trends Endocrinol Metab 21:353-61
Timmons, Brenda C; Fairhurst, Anna-Marie; Mahendroo, Mala S (2009) Temporal changes in myeloid cells in the cervix during pregnancy and parturition. J Immunol 182:2700-7
Read, Charles P; Word, R Ann; Ruscheinsky, Monika A et al. (2007) Cervical remodeling during pregnancy and parturition: molecular characterization of the softening phase in mice. Reproduction 134:327-40
Timmons, Brenda C; Mahendroo, Mala (2007) Processes regulating cervical ripening differ from cervical dilation and postpartum repair: insights from gene expression studies. Reprod Sci 14:53-62

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