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

References 

  1. Junqueira LC, Zugaib M, Montes GS, Toledo OM, Krisztan RM, Shigihara KM. Morphologic and histochemical evidence for the occurrence of collagenolysis and for the role of neutrophilic polymorphonuclear leukocytes during cervical dilation. Am J Obstet Gynecol. 1980;138:273–281
  2. Kleissl HP, van der Rest M, Naftolin F, Glorieux FH, de Leon A. Collagen changes in the human uterine cervix at parturition. Am J Obstet Gynecol. 1978;130:748–753
  3. Maillot KV, Zimmermann BK. The solubility of collagen of the uterine cervix during pregnancy and labour. Arch Gynecol. 1976;220:275–280
  4. Osman I, Young A, Ledingham MA, et al. Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod. 2003;9:41–45
  5. Osmers RG, Blaser J, Kuhn W, Tschesche H. Interleukin-8 synthesis and the onset of labor. Obstet Gynecol. 1995;86:223–229
  6. Rajabi MR, Dodge GR, Solomon S, Poole AR. Immunochemical and immunohistochemical evidence of estrogen-mediated collagenolysis as a mechanism of cervical dilatation in the guinea pig at parturition. Endocrinology. 1991;128:371–378
  7. Sakamoto Y, Moran P, Searle RF, Bulmer JN, Robson SC. Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening. Clin Exp Immunol. 2004;138:151–157
  8. Word RA, Landrum CP, Timmons BC, Young SG, Mahendroo MS. Transgene insertion on mouse chromosome 6 impairs function of the uterine cervix and causes failure of parturition. Biol Reprod. 2005;73:1046–1056
  9. Berghella V, Iams JD, Newman RB, et al. Frequency of uterine contractions in asymptomatic pregnant women with or without a short cervix on transvaginal ultrasound scan. Am J Obstet Gynecol. 2004;191:1253–1256
  10. Danforth DN, Buckingham JC, Roddick JW. Connective tissue changes incident to cervical effacement. Am J Obstet Gynecol. 1960;80:939–945
  11. Petersen LK, Uldbjerg N. Cervical collagen in non-pregnant women with previous cervical incompetence. Eur J Obstet Gynecol Reprod Biol. 1996;67:41–45
  12. Sennstrom MB, Ekman G, Westergren-Thorsson G, et al. Human cervical ripening, an inflammatory process mediated by cytokines. Mol Hum Reprod. 2000;6:375–381
  13. Sennstrom MK, Brauner A, Lu Y, Granstrom LM, Malmstrom AL, Ekman GE. Interleukin-8 is a mediator of the final cervical ripening in humans. Eur J Obstet Gynecol Reprod Biol. 1997;74:89–92
  14. Stjernholm-Vladic Y, Stygar D, Mansson C, et al. Factors involved in the inflammatory events of cervical ripening in humans. Reprod Biol Endocrinol. 2004;2:74
  15. Strange K. The end of ”naive reductionism”: rise of systems biology or renaissance of physiology?. Am J Physiol Cell Physiol. 2005;288:C968–C974
  16. Barabasi AL, Oltvai ZN. Network biology: understanding the cell’s functional organization. Nat Rev Genet. 2004;5:101–113
  17. Bugrim A, Nikolskaya T, Nikolsky Y. Early prediction of drug metabolism and toxicity: systems biology approach and modeling. Drug Discov Today. 2004;9:127–135
  18. Hassan SS, Romero R, Haddad R, et al. The transcriptome of the uterine cervix before and after spontaneous term parturition. Am J Obstet Gynecol. 2006;195:778–786
  19. Huber A, Hudelist G, Czerwenka K, Husslein P, Kubista E, Singer CF. Gene expression profiling of cervical tissue during physiological cervical effacement. Obstet Gynecol. 2005;105:91–98
  20. Brazhnik P, de la Fuente A, Mendes P. Gene networks: how to put the function in genomics. Trends Biotechnol. 2002;20:467–472
  21. Draghici S, Khatri P, Martins RP, Ostermeir GC, Krawetz SA. Global functional profiling of gene expression. Genomics. 2003;81:98–104
  22. Draghici S, Khatri P, Tarca AL, et al. A systems biology approach for pathway level analysis. Genome Research. 2007;in press.
  23. Benjamini Y, Drai D, Elmer G, Kafkafi N, Golani I. Controlling the false discovery rate in behavior genetics research. Behav Brain Res. 2001;125:279–284
  24. Auffray C, Imbeaud S, Roux-Rouquie M, Hood L. From functional genomics to systems biology: concepts and practices. C R Biol. 2003;326:879–892
  25. Fraser AG, Marcotte EM. Development through the eyes of functional genomics. Curr Opin Genet Dev. 2004;14:336–342
  26. Kitano H. Computational systems biology. Nature. 2002;420:206–210
  27. Word RA, Li XH, Hnat M, Carrick K. Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts. Semin Reprod Med. 2007;25:69–79
  28. Liggins G. Cervical ripening as an inflammatory reaction. In:  Ellwood D,  Anderson A editor. The cervix in pregnancy and labour. Edinburgh: Churchill Livingstone; 1981;p. 1–9
  29. Tornblom SA, Klimaviciute A, Bystrom B, Chromek M, Brauner A, Ekman-Ordeberg G. Non-infected preterm parturition is related to increased concentrations of IL-6, IL-8 and MCP-1 in human cervix. Reprod Biol Endocrinol. 2005;3:39
  30. Young A, Thomson AJ, Ledingham M, Jordan F, Greer IA, Norman JE. Immunolocalization of proinflammatory cytokines in myometrium, cervix, and fetal membranes during human parturition at term. Biol Reprod. 2002;66:445–449
  31. Plow EF, Herren T, Redlitz A, Miles LA, Hoover-Plow JL. The cell biology of the plasminogen system. FASEB J. 1995;9:939–945
  32. Tsatas D, Baker MS, Rice GE. Differential expression of proteases in human gestational tissues before, during and after spontaneous-onset labour at term. J Reprod Fertil. 1999;116:43–49
  33. Koelbl H, Kirchheimer J, Tatra G. Influence of delivery on plasminogen activator inhibitor activity. J Perinat Med. 1989;17:107–111
  34. Calandra T, Bucala R. Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Crit Rev Immunol. 1997;17:77–88
  35. Chaiworapongsa T, Romero R, Espinoza J, et al. Macrophage migration inhibitory factor in patients with preterm parturition and microbial invasion of the amniotic cavity. J Matern Fetal Neonatal Med. 2005;18:405–416
  36. Wang H, Stjernholm YV. Plasma membrane receptor mediated MAPK signaling pathways are activated in human uterine cervix at parturition. Reprod Biol Endocrinol. 2007;5:3
  37. Salomonis N, Cotte N, Zambon AC, et al. Identifying genetic networks underlying myometrial transition to labor. Genome Biol. 2005;6:R12

 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