American Journal of Obstetrics & Gynecology
Volume 197, Issue 3 , Pages 250.e1-250.e7, September 2007

Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition

Presented at the 27th Annual Scientific Meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 5-10, 2007.

  • Sonia S. Hassan, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI
    • Corresponding Author InformationReprints: Sonia S. Hassan, MD, and Roberto Romero, MD, Perinatology Research Branch, NICHD, NIH, DHHS, Wayne State University/Hutzel Women’s Hospital, 3990 John R, Box #4, Detroit, MI 48201
    • ,
  • Roberto Romero, MD

      Affiliations

    • Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI
    • ,
  • Adi L. Tarca, PhD

      Affiliations

    • Department of Computer Science, Wayne State University, Detroit, MI
    • ,
  • Sorin Draghici, PhD

      Affiliations

    • Department of Computer Science, Wayne State University, Detroit, MI
    • ,
  • Beth Pineles

      Affiliations

    • Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI
    • ,
  • Andrej Bugrim, PhD

      Affiliations

    • GeneGo, Inc, St. Joseph, MI.
    • ,
  • Nahla Khalek, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • ,
  • Natalia Camacho, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • ,
  • Pooja Mittal, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • ,
  • Bo Hyun Yoon, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
    • ,
  • Jimmy Espinoza, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI
    • ,
  • Chong Jai Kim, MD, PhD

      Affiliations

    • Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, MI
    • ,
  • Yoram Sorokin, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
    • ,
  • John Malone Jr, MD

      Affiliations

    • Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI

Objective

This study aimed to discover “signature pathways” that characterize biologic processes, based on genes differentially expressed in the uterine cervix before and after spontaneous labor.

Study Design

The cervical transcriptome was characterized previously from biopsy specimens taken before and after term labor. Pathway analysis was used to study the differentially expressed genes, based on 2 gene-to-pathway annotation databases (Kyoto Encyclopedia of Genes and Genomes [Kanehisa Laboratories, Kyoto University, Kyoto, Japan] and Metacore software [GeneGo, Inc, St. Joseph, MI]). Overrepresented and highly impacted pathways and connectivity nodes were identified.

Results

Fifty-two pathways in the Metacore database were enriched significantly in differentially expressed genes. Three of the top 5 pathways were known to be involved in cervical remodeling. Two novel pathways were plasmin signaling and plasminogen activator urokinase signaling. The same analysis with the Kyoto Encyclopedia of Genes and Genomes database identified 4 significant pathways that the impact analysis confirmed. Multiple nodes that provide connectivity within the plasmin and plasminogen activator urokinase signaling pathways were identified.

Conclusion

Three strategies for pathway analysis were consistent in their identification of novel, unexpected, and expected pathways, which suggests that this approach is both valid and effective for the elucidation of biologic mechanisms that are involved in cervical dilation and remodeling.

Key words: cervical dilation, cervical remodeling, cervix, gene signature network, labor, microarray, parturition, pathway analysis, plasmin, systems biology

 

 Supported in part by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. SD has been supported in part by the following grants: NSF DB1-0234806, CCF-0438970, 1RH01HG003491-01A1, 1U01CA117478-01, 1R21CA 100740-01, 1R01NS045207-01, 5R21EB000990-03, 2P30CA022453-24.

 Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the NSF, NIH, DOD, or any other of the funding agencies.

 Cite this article as: Hassan SS, Romero R, Tarca AL, et al. Signature pathways identified from gene expression profiles in the human uterine cervix before and after spontaneous term parturition. Am J Obstet Gynecol 2007;197:250.e1-250.e7.

PII: S0002-9378(07)00875-7

doi:10.1016/j.ajog.2007.07.008

American Journal of Obstetrics & Gynecology
Volume 197, Issue 3 , Pages 250.e1-250.e7, September 2007

Article Tools

* Image Usage & Resolution