Skip to main content
SpringerLink
Log in

Choriodecidual Inflammation: A Harbinger of the Preterm Labor Syndrome

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

Abstract

Causal, cellular, and inflammatory links between choriodecidual infection with group B streptococcus (GBS) and preterm labor were assessed in a nonhuman primate model. Rhesus monkeys received varying doses of a clinical isolate of GBS, type III or saline, via an indwelling catheter placed between the chorion/decidua and myometrium in the lower pole of the uterus. Choriodecidual inoculation of GBS was followed by a graded response in amniotic fluid (AF) leukocytes, proinflammatory cytokines, prostaglandin E2 and F2α, and uterine activity (P < .05). The magnitude of the inflammatory response in AF was related, in part, to the initial inoculum size and whether AF cultures remained negative or became positive for GBS. Microbial invasion ofAF was associated with advanced inflammation and preterm labor. We provide experimental evidence that chorio deciduitis is a transitional stage of intrauterine infection, which may be self-limited, remain dormant, or progress to intraamniotic infection. These data, coupled with clinical observations, suggest that choriodecidual inflammation is an antecedent event in the pathogenesis of premature cervical ripening functional cervical insufficiency), premature rupture of the fetal membranes, or preterm labor.

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. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med. 1988;319(15):972–978.

    Article  CAS  PubMed  Google Scholar 

  2. Romero R, Mazor M. Infection and preterm labor. Clin Obstet Gynecol. 1988;31(3):553–584.

    Article  CAS  PubMed  Google Scholar 

  3. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75–84.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Romero R, Espinoza J, Goncalves LF, Kusanovic JP, Friel LA, Nien JK. Inflammation in preterm and term labour and delivery. Semin Fetal Neonatal Med. 2006;11(5):317–326.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cassell GH, Waites KB, Crouse DT. Mycoplasmal infections. In: Remington JS, Klein JO, eds. Infectious Diseases of the Fetus and Newborn Infant. Philadelphia, PA: W. B. Saunders Co., Inc; 2001:733–767.

    Google Scholar 

  6. Davies JK, Shikes RH, Sze CI, et al. Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection. Am J Obstet Gynecol. 2000; 183(5):1088–1093.

    Article  CAS  PubMed  Google Scholar 

  7. Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis. 1982;145(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  8. McDonald HM, O’Loughlin JA, Jolley P, Vigneswaran R, McDonald PJ. Vaginal infection and preterm labour. Br J Obstet Gynaecol. 1991;98(5):427–435.

    Article  CAS  PubMed  Google Scholar 

  9. Cassell GH, Andrew W, Haut J. Isolation of micro-organisms from chorioamnion is twice that from amniotic fluid at cesarean delivery in women with intact membranes. Am J Obstet Gynecol, 1993;168(1):p.424.

  10. Elovitz MA, Mrinalini C. Animal models of preterm birth. Trends Endocrinol Metab. 2004;15(10):479–487.

    Article  CAS  PubMed  Google Scholar 

  11. Gravett MG, Witkin SS, Haluska GJ, Edwards JL, Cook MJ, Novy MJ. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171(6):1660–1667.

    Article  CAS  PubMed  Google Scholar 

  12. Gravett MG, Novy MJ, Rosenfeld RG, et al. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA. 2004;292(4):462–469.

    Article  CAS  PubMed  Google Scholar 

  13. Gravett MG, Thomas A, Schneider KA, et al. Proteomic analysis of cervical-vaginal fluid: identification of novel biomarkers for detection of intra-amniotic infection. J Proteome Res. 2007;6(1):89–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Gravett MG, Adams KM, Sadowsky DW, et al. Immunomodulators plus antibiotics delay preterm delivery after experimental intraamniotic infection in a nonhuman primate model. Am J Obstet Gynecol. 2007;197(5):518e1–518e8.

    Article  CAS  Google Scholar 

  15. Vadillo-Ortega F, Sadowsky DW, Haluska GJ, et al. Identification of matrix metalloproteinase-9 in amniotic fluid and amniochorion in spontaneous labor and after experimental intrauterine infection or interleukin-1 beta infusion in pregnant rhesus monkeys. Am J Obstet Gynecol. 2002;186(1): 128–138.

    Article  CAS  PubMed  Google Scholar 

  16. Bethea CL, Gravett MG, Sadowsky DW, et al. Amniotic fluid prolactin is decreased by experimental intrauterine infection or interleukin-1beta infusion but not via prostaglandins in pregnant rhesus macaques. Biol Reprod. 1998;58(6): 1385–1393.

    Article  CAS  PubMed  Google Scholar 

  17. Sadowsky DW, Adams KM, Gravett MG, Witkin SS, Novy MJ. Preterm labor is induced by intraamniotic infusions of interleukin-1beta and tumor necrosis factor-alpha but not by interleukin-6 or interleukin-8 in a nonhuman primate model. Am J Obstet Gynecol. 2006;195(6):1578–1589.

    Article  CAS  PubMed  Google Scholar 

  18. Gravett MD, Witkin SS, Novy MJ. A nonhuman primate model for chorioamnionitis and preterm labor. Sem Reprod Endocrinol. 1994;12(4):246–262.

    Article  Google Scholar 

  19. Gray DJ, Robinson HB, Malone J, Thomson RB Jr. Adverse outcome in pregnancy following amniotic fluid isolation of Ureaplasma urealyticum. Prenat Diagn. 1992;12(2): 111–117.

    Article  CAS  PubMed  Google Scholar 

  20. Yellon SM, Mackler AM, Kirby MA. The role of leukocyte traffic and activation in parturition. J Soc Gynecol Investig. 2003;10(6):323–338.

    Article  CAS  PubMed  Google Scholar 

  21. Menon R, Fortunato SJ. The role of matrix degrading enzymes and apoptosis in rupture of membranes. J Soc Gynecol Investig. 2004;11(7):427–437.

    Article  CAS  PubMed  Google Scholar 

  22. Zaga-Clavellina V, Merchant-Larios H, Garcia-Lopez G, Maida-Claros R, Vadillo-Ortega F. Differential secretion of matrix metalloproteinase-2 and –9 after selective infection with group B streptococci in human fetal membranes. J Soc Gynecol Investig. 2006;13(4): 271–279.

    Article  CAS  Google Scholar 

  23. Kelly RW. Inflammatory mediators and cervical ripening. J Reprod Immunol. 2002;57(1–2):217–224.

    Article  CAS  PubMed  Google Scholar 

  24. Cox SM, King MR, Casey ML, MacDonald PC. Interleukin-1 beta, -1 alpha, and –6 and prostaglandins in vaginal/cervical fluids of pregnant women before and during labor. J Clin Endocrinol Metab. 1993;77(3):805–815.

    CAS  PubMed  Google Scholar 

  25. Malak TM, Bell SC. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet Gynaecol. 1994;101(5):375–386.

    Article  CAS  PubMed  Google Scholar 

  26. El Khwad M, Stetzer B, Moore RM, et al. Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor. Biol Reprod. 2005; 72(3):720–726.

  27. Reti NG, Lappas M, Riley C, et al. Why do membranes rupture at term? Evidence of increased cellular apoptosis in the supracervical fetal membranes. Am J Obstet Gynecol. 2007; 196(5):484e1–484e10.

  28. Shim SS, Romero R, Hong JS, et al. Clinical significance of intra-amniotic inflammation in patients with preterm premature rupture of membranes. Am J Obstet Gynecol. 2004;191(4): 1339–1345.

    Article  PubMed  Google Scholar 

  29. Lee SE, Romero R, Jung H, Park CW, Park JS, Yoon BH. The intensity of the fetal inflammatory response in intraamniotic inflammation with and without microbial invasion of the amniotic cavity. Am J Obstet Gynecol. 2007;197(3): 294e1–294e6.

    Article  CAS  Google Scholar 

  30. Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. Ultrasonographic assessment of the uterine cervix and interleukin-8 concentrations in cervical secretions predict intrauterine infection in patients with preterm labor and intact membranes. Ultrasound Obstet Gynecol. 1998; 12(2):86–92.

    Article  CAS  PubMed  Google Scholar 

  31. Andrews WW, Hauth JC, Goldenberg RL, Gomez R, Romero R, Cassell GH. Amniotic fluid interleukin-6: correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol. 1995;173(2):606–612.

    Article  CAS  PubMed  Google Scholar 

  32. Holst RM, Mattsby-Baltzer I, Wennerholm UB, Hagberg H, Jacobsson B. Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery. Acta Obstet Gynecol Scand. 2005;84(6):551–557.

    Article  PubMed  Google Scholar 

  33. Jacobsson B. Intra-amniotic infection and inflammation in preterm birth—is bacteria always the connection? Commentary on the article by Miralles et al. on page 570. Pediatr Res. 2005;57(4):473–474.

    Article  PubMed  Google Scholar 

  34. Zaga-Clavellina V, Garcia-Lopez G, Flores-Herrera H, et al. In vitro secretion profiles of interleukin (IL)–1beta, IL-6, IL-8, IL-10, and TNF alpha after selective infection with Escherichia coli in human fetal membranes. Reprod Biol Endocrinol, 2007;13(5):p.46.

  35. Steel JH, Malatos S, Kennea N, et al. Bacteria and inflammatory cells in fetal membranes do not always cause preterm labor. Pediatr Res. 2005;57(3):404–411.

    Article  PubMed  Google Scholar 

  36. Park CW, Moon KC, Park JS, Jun JK, Romero R, Yoon BH. The involvement of human amnion in histologic chorioamnionitis is an indicator that a fetal and an intra-amniotic inflammatory response is more likely and severe: clinical implications. Placenta. 2009;30(1):56–61.

    Article  CAS  PubMed  Google Scholar 

  37. Gomez R, Romero R, Medina L, et al. Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes. Am J Obstet Gynecol. 2005;192(2):350–359.

    Article  CAS  PubMed  Google Scholar 

  38. Buhimschi IA, Jabr M, Buhimschi CS, Petkova AP, Weiner CP, Saed GM. The novel antimicrobial peptide beta3-defensin is produced by the amnion: a possible role of the fetal membranes in innate immunity of the amniotic cavity. Am J Obstet Gynecol. 2004;191(5):1678–1687.

    Article  CAS  PubMed  Google Scholar 

  39. Espinoza J, Chaiworapongsa T, Romero R, et al. Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes. J Matern Fetal Neonatal Med. 2003;13(1):2–21.

    Article  CAS  PubMed  Google Scholar 

  40. Galask R, Varner M, Petzold C, Wilbur S. Bacterial attachment to the chorioamniotic membranes. Am J Obstetr Gynecol. 1984;148(7):915–926.

    Article  CAS  Google Scholar 

  41. Winram SB, Jonas M, Chi E, Rubens CE. Characterization of group B streptococcal invasion of human chorion and amnion epithelial cells in vitro. Infect Immun. 1998;66(10): 4932–4941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kjaergaard N, Helmig RB, Schonheyder HC, Uldbjerg N, Hansen ES, Madsen H. Chorioamniotic membranes constitute a competent barrier to group b streptococcus in vitro. Eur J Obstet Gynecol Reprod Biol. 1999;83(2):165–169.

  43. Gyr TN, Malek A, Mathez-Loic F, et al. Permeation of human chorioamniotic membranes by Escherichia coli in vitro. Am J Obstet Gynecol. 1994;170(1 pt 1):223–227.

    Article  CAS  PubMed  Google Scholar 

  44. Cassell GH, Davis RO, Waites KB, et al. Isolation of Mycoplasma hominis and Ureaplasma urealyticum from amniotic fluid at 16–20 weeks of gestation: potential effect on outcome of pregnancy. Sex Transm Dis. 1983;10(4 suppl): 294–302.

    CAS  PubMed  Google Scholar 

  45. Waites KB, Katz B, Schelonka RL. Mycoplasmas and ureaplasmas as neonatal pathogens. Clin Microbiol Rev. 2005;18(4):757–789.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Waites KB, Schelonka RL, Xiao L, Grigsby PL, Novy MJ. Congenital and opportunistic infections: Ureaplasma species and Mycoplasma hominis. Semin Fetal Neonatal Med, 2009; 14(4):p.190.

  47. Lockwood CJ, Paidas M, Krikun G, et al. Inflammatory cytokine and thrombin regulation of interleukin-8 and intercellular adhesion molecule-1 expression in first trimester human decidua. J Clin Endocrinol Metab. 2005;90(8):4710–4715.

  48. Bryant-Greenwood GD, Kern A, Yamamoto SY, Sadowsky DW, Novy MJ. Relaxin and the human fetal membranes. Reprod Sci. 2007;14(8 suppl):42–45.

    Article  CAS  PubMed  Google Scholar 

  49. Lockwood CJ. Biochemical markers of preterm delivery. In: Petraglia F et al, eds. Preterm Birth: Mechanisms, Mediators, Prediction, Prevention and Interventions. United Kingdom: Informa Healthcare; 2007:115–130.

    Google Scholar 

  50. Keeler SM, Roman AS, Coletta JM, Kiefer DG, Feuerman M, Rust OA. Fetal fibronectin testing in patients with short cervix in the midtrimester: can it identify optimal candidates for ultrasound-indicated cerclage? Am J Obstet Gynecol. 2009; 200(2):158e1–158e6.

  51. Christiaens I, Zaragoza DB, Guilbert L, Robertson SA, Mitchell BF, Olson DM. Inflammatory processes in preterm and term parturition. J Reprod Immunol. 2008;79(1):50–57.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Reproductive Sciences, Oregon National Primate Research Center, 505 NW 185th Ave, Beaverton, Oregon, 97006, USA

    Peta L. Grigsby PhD, Miles J. Novy MD & Drew W. Sadowsky PhD

  2. Department of Obstetrics & Gynecology, University of Washington, Washington, Seattle, USA

    Kristina M. Adams Waldorf MD & Michael G. Gravett MD

  3. Human Immunogenetics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    Kristina M. Adams Waldorf MD

Authors
  1. Peta L. Grigsby PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Miles J. Novy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristina M. Adams Waldorf MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Drew W. Sadowsky PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael G. Gravett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peta L. Grigsby PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grigsby, P.L., Novy, M.J., Waldorf, K.M.A. et al. Choriodecidual Inflammation: A Harbinger of the Preterm Labor Syndrome. Reprod. Sci. 17, 85–94 (2010). https://doi.org/10.1177/1933719109348025

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719109348025

KEY words

Search

Navigation