Skip to main content

Advertisement

SpringerLink
Log in

Molecular Markers of Preterm Labor in the Choriodecidua

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Because relevant biochemical changes are known to begin at the choriodecidual interface some weeks before actual clinical onset of labor, we hypothesized that the preterm choriodecidua may display gene and protein expression patterns specific to preterm labor. Transcriptomic (microarray) and proteomic (2-dimensional gel electrophoresis [2DGE]) profiling methodologies were used to compare changes in choriodecidual tissue collected from women who delivered before 35 weeks of gestation following spontaneous preterm labor (n = 12) and gestation-matched nonlaboring controls (n = 7). Additionally, 2DGE was used to compare differences in protein expression during term and preterm labor and to construct a choriodecidual proteome map. Overall, expressed transcripts and proteins indicated active tissue remodeling independent of labor status and an association with inflammatory processes during labor. Spontaneous, infection-induced and abruption-associated preterm deliveries were each defined by distinct transcriptional profiles. Proteins osteoglycin and progesterone receptor component 2 (PGRMC2) were upregulated during term and preterm labor while galectin 1, annexin 3, annexin 5, and protein disulfide isomerase (PDI) were upregulated only during preterm labor, suggesting a probable association with the underlying pathology. Together, these results represent novel data that warrant further investigations to elucidate plausible causal relationships of these molecules with spontaneous preterm delivery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Romero R, Espinoza J, Kusanovic JP, et al. The preterm parturition syndrome. BJOG. 2006;113(suppl 3):17–42.

    Article  CAS  Google Scholar 

  2. Bell SC, Malak TM. Structural and Cellular Biology of the Fetal Membranes. In: Elder MG, Romero R, Lamont RF, eds. Preterm Labour. New York: Churchill Livingstone; 1997: 401–428.

    Google Scholar 

  3. Goldenberg RL, Iams JD, Mercer BM, et al. The Preterm Prediction Study: toward a multiple-marker test for spontaneous preterm birth. Am J Obstet Gynecol. 2001;185(3):643–651.

    Article  CAS  Google Scholar 

  4. Haddad R, Tromp G, Kuivaniemi H, et al. Human spontaneous labor without histologic chorioamnionitis is characterized by an acute inflammation gene expression signature. Am J Obstet Gynecol. 2006;195(2):394 e391–324.

    Article  Google Scholar 

  5. Ramagli LS. Quantifying protein in 2D PAGE Solubilization Buffers. In: Link Andrew, ed. Methods in Molecular Biology Vol 112: 2D Proteome Analysis Protocols. New Jersey: Humana Press Inc; 1999:99–103.

    Google Scholar 

  6. Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol. 2003;24(1):25–29.

    Article  CAS  Google Scholar 

  7. Croker BA, Krebs DL, Zhang JG, et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003;4(6): 540–545.

    Article  CAS  Google Scholar 

  8. Ognjanovic S, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes. Am J Obst Gynecol. 2002;187(4):1051–1058.

    Article  CAS  Google Scholar 

  9. Yasukawa H, Ohishi M, Mori H, et al. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macro-phages. Nat Immunol. 2003;4(6):551–556.

    Article  CAS  Google Scholar 

  10. Laham N, Brennecke SP, Bendtzen K, Rice GE. Differential release of interleukin-6 from human gestational tissues in association with labour and in vitro endotoxin treatment. J Endocrinol. 1996;149(3):431–439.

    Article  CAS  Google Scholar 

  11. Salmon JE, Girardi G, Holers VM. Complement activation as a mediator of antiphospholipid antibody induced pregnancy loss and thrombosis. Ann Rheum Dis. 2002;61(suppl 2):ii46–ii50.

    Article  CAS  Google Scholar 

  12. Takeuchi O, Sato S, Horiuchi T, et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J Immunol. 2002;169(1):10–14.

    Article  CAS  Google Scholar 

  13. Lockwood CJ, Toti P, Arcuri F, et al. Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua. Am J Pathol. 2005;167(5):1443–1449.

    Article  CAS  Google Scholar 

  14. Hayashi F, Means TK, Luster AD. Toll-like receptors stimulate human neutrophil function. Blood. 2003;102(7): 2660–2669.

    Article  CAS  Google Scholar 

  15. Fortunato SJ, Menon R. Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes. Am J Obstet Gynecol. 2001;184(7):1399–1405; discussion 1405–1396.

    Article  CAS  Google Scholar 

  16. Huang Y, Zhao Q, Chen GQ. Phospholipid scramblase 1. Sheng Li Xue Bao. 2006;58(6):501–510.

    CAS  PubMed  Google Scholar 

  17. Hart SP, Dougherty GJ, Haslett C, Dransfield I. CD44 regulates phagocytosis of apoptotic neutrophil granulocytes, but not apoptotic lymphocytes, by human macrophages. J Immunol. 1997;159(2):919–925.

    CAS  PubMed  Google Scholar 

  18. Gottlieb RA, Kitsis RN. Seeing death in the living. Nat Med. 2001;7(12):1277–1278.

    Article  CAS  Google Scholar 

  19. Leroy MJ, Dallot E, Czerkiewicz I, Schmitz T, Breuiller-Fouche M. Inflammation of choriodecidua induces tumor necrosis factor alpha-mediated apoptosis of human myometrial cells. Biol Reprod. 2007;76(5):769–776.

    Article  CAS  Google Scholar 

  20. Gaur U, Aggarwal BB. Regulation of proliferation, survival and apoptosis by members of the TNF superfamily. Biochem Pharmacol. 2003;66(8):1403–1408.

    Article  CAS  Google Scholar 

  21. Liu H, Ma Y, Pagliari LJ, et al. TNF-alpha-induced apoptosis of macrophages following inhibition of NF-kappa B: a central role for disruption of mitochondria. J Immunol. 2004;172(3): 1907–1915.

    Article  CAS  Google Scholar 

  22. Alexander JM, Bikkal HA, Zervas NT, Laws ER Jr, Klibanski A. Tumor-specific expression and alternate splicing of messenger ribonucleic acid encoding activin/transforming growth factor-beta receptors in human pituitary adenomas. J Clin Endocrinol Metab. 1996;81(2):783–790.

    CAS  PubMed  Google Scholar 

  23. Krause CD, He W, Kotenko S, Pestka S. Modulation of the activation of Stat1 by the interferon-gamma receptor complex. Cell Res. 2006;16(1):113–123.

    Article  CAS  Google Scholar 

  24. Lappas M, Permezel M, Georgiou HM, Rice GE. Regulation of proinflammatory cytokines in human gestational tissues by peroxisome proliferator-activated receptor-gamma: effect of 15-deoxy-Delta(12,14)-PGJ(2) and troglitazone. J Clin Endocrinol Metab. 2002;87(10):4667–4672.

    Article  CAS  Google Scholar 

  25. Monick MM, Robeff PK, Butler NS, et al. Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA. J Biol Chem. 2002;277(36):32992–33000.

    Article  CAS  Google Scholar 

  26. Shanahan CM, Cary NR, Osbourn JK, Weissberg PL. Identification of osteoglycin as a component of the vascular matrix. Differential expression by vascular smooth muscle cells during neointima formation and in atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 1997;17(11):2437–2447.

    Article  CAS  Google Scholar 

  27. Schultz-Norton JR, McDonald WH, Yates JR, Nardulli AM. Protein disulfide isomerase serves as a molecular chaperone to maintain estrogen receptor alpha structure and function. Mol Endocrinol. 2006;20(9):1982–1995.

    Article  CAS  Google Scholar 

  28. Winkler M, Kemp B, Classen-Linke I, et al. Estrogen receptor alpha and progesterone receptor A and B concentration and localization in the lower uterine segment in term parturition. J Soc Gynecol Investig. 2002;9(4):226–232.

    CAS  PubMed  Google Scholar 

  29. Morrison JJ, Charnock-Jones DS, Smith SK. Messenger RNA encoding thiol protein disulphide isomerase in amnion, chorion and placenta in human term and preterm labour. Br J Obstet Gynaecol. 1996;103(9):873–878.

    Article  CAS  Google Scholar 

  30. Hirai Y, Utsugi K, Takeshima N, et al. Putative gene loci associated with carcinogenesis and metastasis of endocervical adenocarcinomas of uterus determined by conventional and array-based CGH. Am J Obstet Gynecol. 2004;191(4):1173–1182.

    Article  CAS  Google Scholar 

  31. Peluso JJ, Pappalardo A, Losel R, Wehling M. Progesterone membrane receptor component 1 expression in the immature rat ovary and its role in mediating progesterone’s antiapoptotic action. Endocrinology. 2006;147(6):3133–3140.

    Article  CAS  Google Scholar 

  32. Pereira L, Reddy AP, Jacob T, et al. Identification of novel protein biomarkers of preterm birth in human cervical-vaginal fluid. J Proteome Res. 2007;6(4):1269–1276.

    Article  CAS  Google Scholar 

  33. Gottlieb RA. Mitochondria and apoptosis. Biol Signals Recept. 2001;10(3–4):147–161.

    Article  CAS  Google Scholar 

  34. Bondanza A, Zimmermann VS, Rovere-Querini P, et al. Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo. J Exp Med. 2004;200(9):1157–1165.

    Article  CAS  Google Scholar 

  35. Rabinovich GA, Daly G, Dreja H, et al. Recombinant galectin-1 and its genetic delivery suppress collagen-induced arthritis via T cell apoptosis. J Exp Med. 1999;190(3):385–398.

    Article  CAS  Google Scholar 

  36. Fortunato SJ, Menon RP, Swan KF, Menon R. Inflammatory cytokine (interleukins 1, 6 and 8 and tumor necrosis factor-alpha) release from cultured human fetal membranes in response to endotoxic lipopolysaccharide mirrors amniotic fluid concentrations. Am J Obstet Gynecol. 1996;174(6): 1855–1861; discussion 1861–1852.

    Article  CAS  Google Scholar 

  37. Challis JRG, Matthews SG, Gibb W, Lye SJ. Endocrine and paracrine regulation of birth at term and preterm. Endocrine Reviews. 2000;21(5):514–550.

    CAS  PubMed  Google Scholar 

  38. Lappas M, Permezel M, Georgiou HM, Rice GE. Nuclear factor kappa B regulation of proinflammatory cytokines in human gestational tissues in vitro. Biol Reprod. 2002;67(2):668–673.

    Article  CAS  Google Scholar 

  39. Marvin KW, Keelan JA, Eykholt RL, Sato TA, Mitchell MD. Use of cDNA arrays to generate differential expression profiles for inflammatory genes in human gestational membranes delivered at term and preterm. Mol Hum Reprod. 2002;8(4):399–408.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics & Gynaecology, The University of Melbourne, Australia

    Renu Shankar PhD, Fiona Cullinane MD & Shaun P. Brennecke MBBS, DPhil

  2. Pregnancy Research Centre, Department of Perinatal Medicine, The Royal Women’s Hospital, Melbourne, Australia

    Renu Shankar PhD, Fiona Cullinane MD & Shaun P. Brennecke MBBS, DPhil

  3. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas, USA

    Matthew P. Johnson PhD & Eric K. Moses PhD

  4. Department of Biochemistry and Molecular Biology, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Australia

    Nicholas A. Williamson PhD & Anthony W. Purcell PhD

Authors
  1. Renu Shankar PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew P. Johnson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicholas A. Williamson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fiona Cullinane MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony W. Purcell PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eric K. Moses PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shaun P. Brennecke MBBS, DPhil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renu Shankar PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shankar, R., Johnson, M.P., Williamson, N.A. et al. Molecular Markers of Preterm Labor in the Choriodecidua. Reprod. Sci. 17, 297–310 (2010). https://doi.org/10.1177/1933719109353454

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719109353454

Key words

Search

Navigation