Abstract

Cesarean delivery (CD) is the most frequently performed major surgical procedure in the industrialized world. Financial and medical considerations have generated pressures to reduce the rate of CD. We posit that the process of myometrial wound healing determines the future morphology, functional behavior and risk of rupture of the uterine scar. Therefore, optimizing myometrial healing after CD will optimize myometrial structural and functional integrity and minimize the risk of uterine scar rupture in a subsequent pregnancy. Previous studies showed that hematopoetic bone marrow stem cells play a crucial role in post-injury healing of the kidney, ligaments and cardiac muscle. We postulate that hematopoetic bone marrow stem cells also participate in the repair of the uterine incision post-CD. We will test this hypothesis in three specific aims using two strains of mice that differ dramatically in their underlying wound healing characteristics. C57BL/6 mice heal predominantly by fibrotic repair while MRL/MPJ heal by regeneration. The first two aims will evaluate the structural and functional aspects of uterine healing while the third aim addresses the role played by hematopoetic stem cells in repair of the uterine incision. We propose to: (1) investigate molecular and structural aspects of uterine wound healing in MRL/MpJ+/+; C57BL/6 ; C57BL/6-Tg(UBC-GFP)30Scha and B6.MRL-Tnfrsf6lpr mice; (2) investigate how uterine scarring alters myometrial function; and (3) investigate the role of stem cells in uterine regeneration/repair using chimeric mice by transplanting bone marrow stem cells from mice expressing ubiquitous green fluorescent protein into C57BL/6 and MRL congenic mice for the same haplotype. The studies outlined in this proposal are likely to open new and promising areas for understanding the mechanisms of uterine healing and thus for identifying strategies for enhancing the integrity of the uterine scar and ultimately for prevention of uterine rupture during trials of labor after prior CD.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD050249-01
Application #
6956386
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ilekis, John V
Project Start
2005-09-10
Project End
2007-08-30
Budget Start
2005-09-10
Budget End
2006-08-30
Support Year
1
Fiscal Year
2005
Total Cost
$81,750
Indirect Cost

  Institution

Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Wehrum, Mark J; Buhimschi, Irina A; Salafia, Carolyn et al. (2011) Accreta complicating complete placenta previa is characterized by reduced systemic levels of vascular endothelial growth factor and by epithelial-to-mesenchymal transition of the invasive trophoblast. Am J Obstet Gynecol 204:411.e1-411.e11
Bhandari, Vineet; Buhimschi, Catalin S; Han, Christina S et al. (2011) Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate. J Matern Fetal Neonatal Med 24:673-9
Abdel-Razeq, Sonya S; Buhimschi, Irina A; Bahtiyar, Mert O et al. (2010) Interpretation of amniotic fluid white blood cell count in ""bloody tap"" amniocenteses in women with symptoms of preterm labor. Obstet Gynecol 116:344-54
Buhimschi, C S; Baumbusch, M A; Dulay, A T et al. (2010) The role of urinary soluble endoglin in the diagnosis of pre-eclampsia: comparison with soluble fms-like tyrosine kinase 1 to placental growth factor ratio. BJOG 117:321-30
Buhimschi, Catalin S; Zhao, Guomao; Sora, Nicoleta et al. (2010) Myometrial wound healing post-Cesarean delivery in the MRL/MpJ mouse model of uterine scarring. Am J Pathol 177:197-207
Buhimschi, Catalin S; Sora, Nicoleta; Zhao, Guomao et al. (2009) Genetic background affects the biomechanical behavior of the postpartum mouse cervix. Am J Obstet Gynecol 200:434.e1-7
Han, Yiping W; Shen, Tao; Chung, Peter et al. (2009) Uncultivated bacteria as etiologic agents of intra-amniotic inflammation leading to preterm birth. J Clin Microbiol 47:38-47
Buhimschi, Catalin S; Baumbusch, Margaret A; Dulay, Antonette T et al. (2009) Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. Am J Pathol 175:958-75
Buhimschi, Catalin S; Bhandari, Vineet; Han, Yiping W et al. (2009) Using proteomics in perinatal and neonatal sepsis: hopes and challenges for the future. Curr Opin Infect Dis 22:235-43
Buhimschi, C S; Dulay, A T; Abdel-Razeq, S et al. (2009) Fetal inflammatory response in women with proteomic biomarkers characteristic of intra-amniotic inflammation and preterm birth. BJOG 116:257-67

Showing the most recent 10 out of 18 publications