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.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Ilekis, John V
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University of Texas Sw Medical Center Dallas
Obstetrics & Gynecology
Schools of Medicine
United States
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Nallasamy, Shanmugasundaram; Yoshida, Kyoko; Akins, Meredith et al. (2017) Steroid Hormones Are Key Modulators of Tissue Mechanical Function via Regulation of Collagen and Elastic Fibers. Endocrinology 158:950-962
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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