The cervical mucus plug: Structured review of the literature

Acta Obstetricia et Gynecologica Scandinavica

Volumn 88, Issue 5, 2009, Pages 502-513

  Becher, Naja ^a   Waldorf, Kristina Adams ^b   Hein, Merete ^a   Uldbjerg, Niels ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Cervical mucus plug; Immunology; Infection; Pregnancy; Preterm delivery

Indexed keywords

ELASTASE; GRANULOCYTE ENZYME; MATRIX METALLOPROTEINASE; MUCIN; PROTEINASE; PROTEINASE INHIBITOR;

ADAPTIVE IMMUNITY; DILUTION; FLOW KINETICS; HUMAN; IMAGING; INFLAMMATION; INNATE IMMUNITY; PRIORITY JOURNAL; REVIEW; UTERINE CERVIX MUCUS; BACTERIAL INFECTION; CHEMISTRY; FEMALE; IMMUNOLOGY; PHYSIOLOGY; PREGNANCY; PREMATURE LABOR; SECRETION; UTERINE CERVIX;

BACTERIAL INFECTIONS; CERVIX MUCUS; CERVIX UTERI; FEMALE; HUMANS; MUCINS; OBSTETRIC LABOR, PREMATURE; PREGNANCY;

EID: 65649111292     PISSN: 00016349     EISSN: 16000412     Source Type: Journal    
DOI: 10.1080/00016340902852898     Document Type: Review

References (88)

1. Daunter B, Counsilman C. Cervical mucus: its structure and possible biological functions. Eur J Obstet Gynecol Reprod Biol. 1980;10:141-61.
2. Elstein M. Cervical mucus: its physiological role and clinical significance. Adv Exp Med Biol. 1982;144:301-18.
3. Hein M, Petersen AC, Helmig RB, Uldbjerg N, Reinholdt J. Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy. Acta Obstet Gynecol Scand. 2005; 84:734-42.
4. Yoneda S, Sakai M, Sasaki Y, Shiozaki A, Hidaka T, Saito S. Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal secretions and preterm labor index based on clinical variables are optimal predictive markers for preterm delivery in patients with intact membranes. J Obstet Gynaecol Res. 2007;33:38-44.
5. Carlstedt I, Sheehan JK. Structure and macromolecular properties of cervical mucus glycoproteins. Symp Soc Exp Biol. 1989;43:289-316.
6. Odeblad E. The functional structure of human cervical mucus. Acta Obstet Gynecol Scand. 1968;47:57-79.
7. Chretien FC, Cohen J, Borg V, Psychoyos A. Human cervical mucus during the menstrual cycle and pregnancy in normal and pathological conditions. J Reprod Med. 1975;14:192-6.
8. Chretien FC. Ultrastructure and variations of human cervical mucus during pregnancy and the menopause. Acta Obstet Gynecol Scand. 1978;57:337-48.
9. Carlstedt I, Sheehan J, Ulmsten U, Wingerup L. Isolation and purification of the mucin component of human cervical mucus. Adv Exp Med Biol. 1982;144:273-5.
10. Carlstedt I, Lindgren H, Sheehan JK, Ulmsten U, Wingerup L. Isolation and characterization of human cervical-mucus glycoproteins. Biochem J. 1983;211:13-22.
11. Elstein M. Functions and physical properties of mucus in the female genital tract. Br Med Bull. 1978;34:83-8.
12. Mezger T. The Rheology Handbook. Hannover: Curt R. Vincent Verlag, 2002.
13. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4: 45-60.
14. Mall AS. Analysis of mucins: role in laboratory diagnosis. J Clin Pathol. 2008;61:1018-24.
15. Habte HH, Kotwal GJ, Lotz ZE, Tyler MG, Abrahams M, Rodriques J, et al. Antiviral activity of purified human breast milk mucin. Neonatology. 2007;92:96-104.
16. Habte HH, de Beer C, Lotz ZE, Tyler MG, Schoeman L, Kahn D, et al. The inhibition of the human immunodeficiency virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay. Virol J. 2008;5:59.
17. Obara M, Hirano H, Ogawa M, Tsubaki H, Hosoya N, Yoshida Y, et al. Changes in molecular weight of hyaluronan and hyaluronidase activity in uterine cervical mucus in cervical ripening. Acta Obstet Gynecol Scand. 2001;80: 492-6.
18. Fischer DC, Kuth A, Winkler M, Handt S, Hauptmann S, Rath W, et al. A large keratan sulfate proteoglycan present in human cervical mucous appears to be involved in the reorganization of the cervical extracellular matrix at term. J Soc Gynecol Investig. 2001;8:277-84.
19. Casalino-Matsuda SM, Monzon ME, Conner GE, Salathe M, Forteza RM. Role of hyaluronan and reactive oxygen species in tissue kallikrein-mediated epidermal growth factor receptor activation in human airways. J Biol Chem. 2004;279: 21606-16.
20. Casalino-Matsuda SM, Monzon ME, Day AJ, Forteza RM. Hyaluronan fragments/CD44 mediate oxidative stress-induced MUC5B up-regulation in airway epithelium. Am J Respir Cell Mol Biol. 2009;40:277-85.
21. Monzon ME, Casalino-Matsuda SM, Forteza RM. Identification of glycosaminoglycans in human airway secretions. Am J Respir Cell Mol Biol. 2006;34:135-41.
22. Pschera H, Larsson B, Kjaeldgaard A. Changes in fatty acid composition of cervical mucus lecithin during pregnancy. Gynecol Obstet Invest. 1989;28:118-22.
23. McCarthy S. Magnetic resonance imaging in obstetrics and gynecology. Magn Reson Imaging. 1986;4:59-66.
24. Daunter B, Chantler EN, Elstein M. The scanning electronmicroscopy of human cervical mucus in the non-pregnant and pregnant states. Br J Obstet Gynaecol. 1976;83:738-43.
25. Grgic O, Matijevic R, Vasilj O. Qualitative glandular cervical score as a potential new sonomorphological parameter in screening for preterm delivery. Ultrasound Med Biol. 2006; 32:/333-8.
26. Eriksen GV, Carlstedt I, Uldbjerg N, Ernst E. Cervical mucins affect the motility of human spermatozoa in vitro. Fertil Steril. 1998;70:350-4.
27. Hein M, Helmig RB, Schonheyder HC, Ganz T, Uldbjerg N. An in vitro study of antibacterial properties of the cervical mucus plug in pregnancy. Am J Obstet Gynecol. 2001;185: 586-92.
28. Hein M, Valore EV, Helmig RB, Uldbjerg N, Ganz T Antimicrobial factors in the cervical mucus plug. Am J Obstet Gynecol. 2002;187:137-44.
29. Helmig R, Uldbjerg N, Ohlsson K. Secretory leukocyte protease inhibitor in the cervical mucus and in the fetal membranes. Eur J Obstet Gynecol Reprod Biol. 1995;59: 95-101.
30. Becher N, Hein M, Danielsen CC, Uldbjerg N. Matrix metalloproteinases and their inhibitors in the cervical mucus plug at term of pregnancy. Am J Obstet Gynecol. 2004;191: 1232-9.
31. Becher N, Hein M, Uldbjerg N, Danielsen CC. Balance between matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in the cervical mucus plug estimated by determination of free non-complexed TIMP. Reprod Biol Endocrinol. 2008;30:45.
32. Chretien FC, Engelmann P, Dubois R. The variation of the mean spinability of human cervical mucus throughout the various stages of reproductive life. Automatic measurement and statistical study. Eur J Obstet Gynecol Reprod Biol. 1979; 9:289-97.
33. Fang C, Kan Y, Hsiao C. Detection of fetal cells from transcervical mucus plug before first-trimester termination of pregnancy by cytokeratin-7 immunohistochemistry. J Obstet Gynaecol Res. 2005;31:500-7.
34. Katz-Jaffe MG, Mantzaris D, Cram DS. DNA identification of fetal cells isolated from cervical mucus: potential for early non-invasive prenatal diagnosis. BJOG. 2005;112:595-600.
35. Mantzaris D, Cram D, Healy C, Howlett D, Kovacs G. Preliminary report: correct diagnosis of sex in fetal cells isolated from cervical mucus during early pregnancy. Aust New Zealand J Obstet Gynaecol. 2005;45:529-32.
36. Kutteh WH, Franklin RD, Dudley DJ, Moghissi K, Gabbe S, Hill III J, et al. Quantification of immunoglobulins and cytokines in human cervical mucus during each trimester of pregnancy. Am J Obstet Gynecol. 2001;184:865-74.
37. Iacobelli S, Garcea N, Angeloni C. Biochemistry of cervical mucus: a comparative analysis of the secretion from preovulatory, postovulatory, and pregnancy periods. Fertil Steril. 1971;22:727-34.
38. Platz-Christensen JJ, Brandberg A, Wiqvist N. Increased prostaglandin concentrations in the cervical mucus of pregnant women with bacterial vaginosis. Prostaglandins. 1992; 43:133-4.
39. Platz-Christensen JJ, Pernevi P, Bokstrom H, Wiqvist N. Prostaglandin E and F2 alpha concentration in the cervical mucus and mechanism of cervical ripening. Prostaglandins. 1997;53:253-61.
40. Bokstrom H, Norstrom A, Wiqvist N. Cervical mucus concentration of prostaglandins E2 and F(2(alpha)) after pretreatment with mifepristone in the first trimester of pregnancy. Prostaglandins. 1995;49:41-8.
41. Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005;192:S36-46.
42. Vogel I, Thorsen P, Curry A, Sandager P, Uldbjerg N. Biomarkers for the prediction of preterm delivery. Acta Obstet Gynecol Scand. 2005;84:516-25.
43. Dowd J, Laham N, Rice G, Brennecke S, Permezel M. Elevated interleukin-8 concentrations in cervical secretions are associated with preterm labour. Gynecol Obstet Invest. 2001;51:165-8.
44. Nenadic DB, Pavlovic MD. Cervical fluid cytokines in pregnant women: relation to vaginal wet mount findings and polymorphonuclear leukocyte counts. Eur J Obstet Gynecol Reprod Biol. 2008;140:165-70.
45. Mondestin-Sorrentino M, Smulian JC, Vintzileos AM, Sor-rentino D, Ananth CV, Sharma S, et al. Variations in cervical IL-10 and IL-8 concentrations throughout gestation in normal pregnancies. Am J Reprod Immunol. 2007;57:482-7.
46. Luo L, Ibaragi T, Maeda M, Nozawa M, Kasahara T, Sakai M, et al. Interleukin-8 levels and granulocyte counts in cervical mucus during pregnancy. Am J Reprod Immunol. 2000;43:78-84.
47. Sakai M, Ishiyama A, Tabata M, Sasaki Y, Yoneda S, Shiozaki A, et al. Relationship between cervical mucus interleukin-8 concentrations and vaginal bacteria in pregnancy. Am J Reprod Immunol. 2004;52:106-12.
48. Hattori Y, Nakanishi T, Ozaki Y, Nozawa K, Sato T, Sugiura-Ogasawara M. Uterine cervical inflammatory cytokines, interleukin-6 and -8, as predictors of miscarriage in recurrent cases. Am J Reprod Immunol. 2007;58:350-7.
49. Carlstedt I, Lindgren H, Sheehan JK. The macromolecular structure of human cervical-mucus glycoproteins. Studies on fragments obtained after reduction of disulphide bridges and after subsequent trypsin digestion. Biochem J. 1983; 213:427-35.
50. Sheehan JK, Carlstedt I. The effect of guanidinium chloride on the behaviour of human cervical-mucus glycoproteins. Evidence for unfolding regions of ordered structure in 6M-guanidinium chloride. Biochem J. 1984;221:499-504.
51. Ogawa M, Hirano H, Tsubaki H, Kodama H, Tanaka T The role of cytokines in cervical ripening: correlations between the concentrations of cytokines and hyaluronic acid in cervical mucus and the induction of hyaluronic acid production by inflammatory cytokines by human cervical fibroblasts. Am J Obstet Gynecol. 1998;179:105-10.
52. Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. The diagnostic value of interleukin-8 and fetal fibronectin concentrations in cervical secretions in patients with preterm labor and intact membranes. J Perinat Med. 1997;25:461-8.
53. Pacora P, Maymon E, Gervasi MT, Gomez R, Edwin SS, Yoon BH, et al. Lactoferrin in intrauterine infection, human parturition, and rupture of fetal membranes. Am J Obstet Gynecol. 2000;183:904-10.
54. Larsen B, Galask RP, Snyder IS. Muramidase and peroxidase activity of human amniotic fluid. Obstet Gynecol. 1974;44: 219-23.
55. Heine RP, Wiesenfeld H, Mortimer L, Greig PC. Amniotic fluid defensins: potential markers of subclinical intrauterine infection. Clin Infect Dis. 1998;27:513-8.
56. Eggert-Kruse W, Botz I, Pohl S, Rohr G, Strowitzki T Antimicrobial activity of human cervical mucus. Hum Reprod. 2000;15:778-84.
57. Moriyama A, Shimoya K, Ogata I, Kimura T, Nakamura T, Wada H, et al. Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle. Mol Hum Reprod. 1999;5:656-61.
58. Cole AM, Dewan P, Ganz T Innate antimicrobial activity of nasal secretions. Infect Immun. 1999;67:3267-75.
59. Marolis GB, Buckley RH, Younger JB. Serum immunogbulin cocentrations during normal pregnancy. Am J Obstet Gynecol. 1971;109:971-6.
60. Saha K, Bhatia G, Mukherjee S, Mitra AB, Luthra UK. Fluctuation of immunoglobulin levels in cervical mucus during the various phases of female reproductive life and its alteration in uterine disorders. Indian J Med Res. 1981;74: 696-704.
61. Jacobsson B, Holst RM, Mattsby-Baltzer I, Nikolaitchouk N, Wennerholm UB, Hagberg H. Interleukin-18 in cervical mucus and amniotic fluid: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation and preterm delivery. BJOG. 2003;110:598-603.
62. 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;84:551-7.
63. Lange M, Chen FK, Wessel J, Buscher U, Dudenhausen JW. Elevation of interleukin-6 levels in cervical secretions as a predictor of preterm delivery. Acta Obstet Gynecol Scand. 2003;82:326-9.
64. Lockwood CJ, Ghidini A, Wein R, Lapinski R, Casal D, Berkowitz RL. Increased interleukin-6 concentrations in cervical secretions are associated with preterm delivery. Am J Obstet Gynecol. 1994;171:1097-102.
65. Jun JK, Yoon BH, Romero R, Kim M, Moon JB, Ki SH, et al. Interleukin 6 determinations in cervical fluid have diagnostic and prognostic value in preterm premature rupture of membranes. Am J Obstet Gynecol. 2000;183:868-73.
66. Rizzo G, Capponi A, Vlachopoulou A, Angelini E, Grassi C, Romanini C. Interleukin-6 concentrations in cervical secretions in the prediction of intrauterine infection in preterm premature rupture of the membranes. Gynecol Obstet Invest. 1998;46:91-5.
67. Rizzo G, Capponi A, Rinaldo D, Tedeschi D, Arduini D, Romanini C. Interleukin-6 concentrations in cervical secretions identify microbial invasion of the amniotic cavity in patients with preterm labor and intact membranes. Am J Obstet Gynecol. 1996;175:812-7.
68. Jacobsson B, Mattsby-Baltzer I, Hagberg H. Interleukin-6 and interleukin-8 in cervical and amniotic fluid: relationship to microbial invasion of the chorioamniotic membranes. BJOG. 2005;112:719-24.
69. Mattsby-Baltzer I, Platz-Christensen JJ, Hosseini N, Rosen P. IL-1(beta), IL-6, TNF(alpha), fetal fibronectin and endotoxin in the lower genital tract of pregnant women with bacterial vaginosis. Acta Obstet Gynecol Scand. 1998;77: 701-6.
70. Sakai M, Sasaki Y, Yoneda S, Kasahara T, Arai T, Okada M, et al. Elevated interleukin-8 in cervical mucus as an indicator for treatment to prevent premature birth and preterm, pre-labor rupture of membranes: a prospective study. Am J Reprod Immunol. 2004;51:220-5.
71. Takemura M, Itoh H, Sagawa N, Yura S, Korita D, Kakui K, et al. Cyclic mechanical stretch augments both interleukin-8 and monocyte chemotactic protein-3 production in the cultured human uterine cervical fibroblast cells. Mol Hum Reprod. 2004;10:573-80.
72. Krumme D, Wallner O, Fritz H. Proteinases and proteinase inhibitors in human cervicla mucus. In: Insler V, Bettendorf G, editors. The uterine cervix in reproduction. Stuttgard: Georg Thieme; 1977. p. 92-100.
73. Limvarapuss C, Kanayama N, Terao T. Elastase activity of endocervical mucus in normal pregnancy. Asia Oceania J Obstet Gynaecol. 1992;18:147-53.
74. Kanayama N, Terao T. The relationship between granulocyte elastase-like activity of cervical mucus and cervical maturation. Acta Obstet Gynecol Scand. 1991;70:29-34.
75. Nakai A, Taniuchi Y, Miyake H, Nakai M, Yokota A, Takeshita T Increased level of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery. Gynecol Obstet Invest. 2005;60:87-91.
76. Balic D, Latifagic A, Hudic I. Insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions as a predictor of preterm delivery. J Matern-Fetal Neonatal Med. 2008;21:297-300.
77. Kekki M, Kurki T, Karkkainen T, Hiilesmaa V, Paavonen J, Rutanen E. Insulin-like growth factor-binding protein-1 in cervical secretion as a predictor of preterm delivery. Acta Obstet Gynecol Scand. 2001;80:546-51.
78. Paternoster DM, Muresan D, Vitulo A, Serena A, Battagliarin G, Dell'avanzo M, et al. Cervical phIGFBP-1 in the evaluation of the risk of preterm delivery. Acta Obstet Gynecol Scand. 2007;86:151-5.
79. Yoon BH, Romero R, Moon JB, Oh SY, Han SY, Kim JC et al. The frequency and clinical significance of intra-amniotic inflammation in patients with a positive cervical fetal fibro-nectin. Am J Obstet Gynecol. 2001;185:1137-42.
80. Sennstrom MB, Granstrom LM, Lockwood CJ, Omazic B, Johansson O, Malmstrom A, et al. Cervical fetal fibronectin correlates to prostaglandin E2-induced cervical ripening and can be identified in cervical tissue. Am J Obstet Gynecol. 1998;178:540-5.
81. Mercorio F, Mercorio A, Votino C, Di Spiezio Sardo A, Barba GV, Nappi C. Fetal fibronectin as predictor of successful induction of mid-trimester abortion. Acta Obstet Gynecol Scand. 2005;84:390-4.
82. Gurbuz A, Karateke A, Ozturkmen M, Kabaca C. Human chorionic gonadotropin assay in cervical secretions for accurate diagnosis of preterm labor. Int J Gynaecol Obstet. 2004; 85:132-8.
83. Takata K, Suganuma N, Wada H, Takeuchi K, Kitamura K, Kanayama N. Human chorionic gonadotropin in cervical fluid as a predictor of miscarriage. Fertil Steril. 2005;84: 687-91.
84. Vaisanen-Tommiska M, Butzow R, Ylikorkala O, Mikkola TS. Mifepristone-induced nitric oxide release and expression of nitric oxide synthases in the human cervix during early pregnancy. Hum Reprod. 2006;21:2180-4.
85. O'Driscoll K, Meagher D, Robson M. Diagnosis of labour. In: Active management of labour. The Duplin experience, 4th edn. Edinbough: Mosby, 2004. pp. 29-32.
86. Romero R, Schaudinn C, Kusanovic JP, Gorur A, Gotsch F, Webster P, et al. Detection of a microbial biofilm in intraamniotic infection. Am J Obstet Gynecol. 2008; 198: 135.e1-135.e5.
87. Kusanovic JP, Espinoza J, Romero R, Goncalves LF, Nien JK, Soto E, et al. Clinical significance of the presence of amniotic fluid 'sludge' in asymptomatic patients at high risk for spontaneous preterm delivery. Ultrasound Obstet Gynecol. 2007;30:706-14.
88. Noori M, Helmig RB, Hein M, Steer PJ. Could a cervical occlusion suture be effective at improving perinatal outcome? BJOG. 2007;114:532-6.