Semin Reprod Med 2007; 25(1): 069-079
DOI: 10.1055/s-2006-956777
Copyright © 2007 by Thieme Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Dynamics of Cervical Remodeling during Pregnancy and Parturition: Mechanisms and Current Concepts

R. Ann Word1 , Xiang-Hong Li1 , Michael Hnat1 , Kelley Carrick2
  • 1Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas
  • 2Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
Further Information

Publication History

Publication Date:
05 January 2007 (online)

ABSTRACT

The cervix serves as a protective barrier from invading microorganisms and as a structural barrier to delivery of the fetus. Among all biological processes, the phenomenal connective tissue remodeling that occurs in the cervix during and after parturition is unparalleled in scope and magnitude. The process of connective tissue remodeling in the cervix during pregnancy occurs in four stages: softening, ripening, dilation, and repair. Although overlapping in time, each stage is uniquely regulated. Results from studies using serial measurements of cervical length indicate that cervical ripening precedes myometrial contractions of labor by several weeks, suggesting that parturition in women is a process of long duration and that uterine contractions of labor are late events in the parturition process. A clear understanding of the biologic mechanisms that regulate cervical remodeling during pregnancy is needed to influence the preterm birth rate and to develop strategies to prevent preterm dilation of the cervix.

REFERENCES

  • 1 Owen J. Evaluation of the cervix by ultrasound for the prediction of preterm birth.  Clin Perinatol. 2003;  30(4) 735-755
  • 2 Yost N P, Cox S M. Infection and preterm labor.  Clin Obstet Gynecol. 2000;  43(4) 759-767
  • 3 Owen J, Iams J D, Hauth J C. Vaginal sonography and cervical incompetence.  Am J Obstet Gynecol. 2003;  188(2) 586-596
  • 4 Andrews W W, Copper R, Hauth J C, Goldenberg R L, Neely C, Dubard M. Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery.  Obstet Gynecol. 2000;  95(2) 222-226
  • 5 Chegini N, Verala J, Luo X, Xu J, Williams R S. Gene expression profile of leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy.  J Soc Gynecol Investig. 2003;  10(3) 161-171
  • 6 Naim A, Haberman S, Burgess T, Navizedeh N, Minkoff H. Changes in cervical length and the risk of preterm labor.  Am J Obstet Gynecol. 2002;  186(5) 887-889
  • 7 Havelock J C, Keller P, Muleba N et al.. Human myometrial gene expression before and during parturition.  Biol Reprod. 2005;  72(3) 707-719
  • 8 Barclay C G, Brennand J E, Kelly R W, Calder A A. Interleukin-8 production by the human cervix.  Am J Obstet Gynecol. 1993;  169(3) 625-632
  • 9 Becher N, Hein M, Danielsen C C, Uldbjerg N. Matrix metalloproteinases and their inhibitors in the cervical mucus plug at term of pregnancy.  Am J Obstet Gynecol. 2004;  191(4) 1232-1239
  • 10 Moriyama A, Shimoya K, Ogata I et al.. Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle.  Mol Hum Reprod. 1999;  5(7) 656-661
  • 11 Pfundt R, van Ruissen F, van Vlijmen-Willems I MJJ et al.. Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia.  J Clin Invest. 1996;  98(6) 1389-1399
  • 12 Mahendroo M S, Porter A, Russell D W, Word R A. The parturition defect in steroid 5alpha-reductase type 1 knockout mice is due to impaired cervical ripening.  Mol Endocrinol. 1999;  13(6) 981-992
  • 13 Minjarez D A, Miller R T, Lindqvist A, Andersson S, Word R A. Regulation of steroid hormone metabolism by 17-hydroxysteroid dehydrogenase type 2 in the human cervix.  J Soc Gynecol Investig. 2000;  7 124A
  • 14 Yoshimatsu K, Sekiya T, Ishihara K, Fukami T, Otabe T, Araki T. Detection of the cervical gland area in threatened preterm labor using transvaginal sonography in the assessment of cervical maturation and the outcome of pregnancy.  Gynecol Obstet Invest. 2002;  53(3) 149-156
  • 15 Shi L, Shi S Q, Saade G R, Chwalisz K, Garfield R E. Studies of cervical ripening in pregnant rats: effects of various treatments.  Mol Hum Reprod. 2000;  6(4) 382-389
  • 16 Garfield R E, Saade G, Buhimschi C et al.. Control and assessment of the uterus and cervix during pregnancy and labour.  Hum Reprod Update. 1998;  4(5) 673-695
  • 17 Buhimschi I A, Dussably L, Buhimschi C S, Ahmed A, Weiner C P. Physical and biomechanical characteristics of rat cervical ripening are not consistent with increased collagenase activity.  Am J Obstet Gynecol. 2004;  191(5) 1695-1704
  • 18 Harkness M LR, Harkness R D. Changes in the physical properties of the uterine cervix of the rat during pregnancy.  J Physiol. 1959;  148 524-547
  • 19 Hollingsworth M, Williams L M. Increases in the creep rate of the rat cervix occurring just prior to parturition.  J Physiol. 1980;  301 90-91
  • 20 Word R A, Landrum C P, Timmons B C, Young S G, Mahendroo M S. Transgene insertion on mouse chromosome 6 impairs function of the uterine cervix and causes failure of parturition.  Biol Reprod. 2005;  73(5) 1046-1056
  • 21 Hindson J C, Schofield B M, Turner C B. Some factors affecting dilatation of the ovine cervix.  Res Vet Sci. 1968;  9(5) 474-480
  • 22 Chwalisz K. The use of progesterone antagonists for cervical ripening and as an adjunct to labour and delivery.  Hum Reprod. 1994;  9(Suppl 1) 131-161
  • 23 Drzewiecki G, Tozzi C, Yu S, Leppert P C. A dual mechanism of biomechanical change in rat cervix in gestation and postpartum: Applied vascular mechanics.  Cardiovasc Eng. 2005;  5(4) 187-193
  • 24 Kokenyesi R, Armstrong L C, Agah A, Artal R, Bornstein P. Thrombospondin 2 deficiency in pregnant mice results in premature softening of the uterine cervix.  Biol Reprod. 2004;  70(2) 385-390
  • 25 Sherwood O D. Relaxin's physiological roles and other diverse actions.  Endocr Rev. 2004;  25(2) 205-234
  • 26 Novak J, Ramirez R J, Gandley R E, Sherwood O D, Conrad K P. Myogenic reactivity is reduced in small renal arteries isolated from relaxin-treated rats.  Am J Physiol Regul Integr Comp Physiol. 2002;  283(2) R349-R355
  • 27 Goldsmith L T, Weiss G, Palejwala S et al.. Relaxin regulation of endometrial structure and function in the rhesus monkey.  Proc Natl Acad Sci USA. 2004;  101(13) 4685-4689
  • 28 Goldsmith L T, Weiss G, Steinetz B G. Relaxin and its role in pregnancy.  Endocrinol Metab Clin North Am. 1995;  24(1) 171-186
  • 29 Isaacs N, James R, Niall H et al.. Relaxin and its structural relationship to insulin.  Nature. 1978;  271(5642) 278-281
  • 30 Schwabe C, Steinetz B, Weiss G et al.. Relaxin.  Recent Prog Horm Res. 1978;  34 123-211
  • 31 Sherwood C D, O'Byrne E M. Purification and characterization of porcine relaxin.  Arch Biochem Biophys. 1974;  160(1) 185-196
  • 32 Haley J, Hudson P, Scanlon D et al.. Porcine relaxin: molecular cloning and cDNA structure.  DNA. 1982;  1(2) 155-162
  • 33 Sakbun V, Ali S M, Greenwood F C, Bryant-Greenwood G D. Human relaxin in the amnion, chorion, decidua parietalis, basal plate, and placental trophoblast by immunocytochemistry and northern analysis.  J Clin Endocrinol Metab. 1990;  70(2) 508-514
  • 34 Hansell D J, Bryant-Greenwood G D, Greenwood F C. Expression of the human relaxin H1 gene in the decidua, trophoblast, and prostate.  J Clin Endocrinol Metab. 1991;  72(4) 899-904
  • 35 Weiss G, Goldsmith L T. Mechanisms of relaxin-mediated premature birth.  Ann NY Acad Sci. 2005;  1041 345-350
  • 36 Hsu S Y, Nakabayashi K, Nishi S et al.. Activation of orphan receptors by the hormone relaxin.  Science. 2002;  295(5555) 671-674
  • 37 Bathgate R A, Ivell R, Sanborn B M, Sherwood O D, Summers R J. Receptors for relaxin family peptides.  Ann NY Acad Sci. 2005;  1041 61-76
  • 38 Krajnc-Franken M A, van Disseldorp A J, Koenders J E, Mosselman S, van Duin M, Gossen J A. Impaired nipple development and parturition in LGR7 knockout mice.  Mol Cell Biol. 2004;  24(2) 687-696
  • 39 Zhao L, Samuel C S, Tregear G W, Beck F, Wintour E M. Collagen studies in late pregnant relaxin null mice.  Biol Reprod. 2000;  63(3) 697-703
  • 40 Zhao L, Roche P J, Gunnersen J M et al.. Mice without a functional relaxin gene are unable to deliver milk to their pups.  Endocrinology. 1999;  140(1) 445-453
  • 41 Zhao S, Sherwood O D. Monoclonal antibodies specific for rat relaxin. X. Endogenous relaxin induces changes in the histological characteristics of the rat vagina during the second half of pregnancy.  Endocrinology. 1998;  139(11) 4726-4734
  • 42 Zhao S, Kuenzi M J, Sherwood O D. Monoclonal antibodies specific for rat relaxin. IX. Evidence that endogenous relaxin promotes growth of the vagina during the second half of pregnancy in rats.  Endocrinology. 1996;  137(2) 425-430
  • 43 Zhao S, Malmgren C H, Shanks R D, Sherwood O D. Monoclonal antibodies specific for rat relaxin. VIII. Passive immunization with monoclonal antibodies throughout the second half of pregnancy reduces water consumption in rats.  Endocrinology. 1995;  136(5) 1892-1897
  • 44 Summerlee A J, Ramsey D G, Poterski R S. Neutralization of relaxin within the brain affects the timing of birth in rats.  Endocrinology. 1998;  139(2) 479-484
  • 45 Hwang J J, Shanks R D, Sherwood O D. Monoclonal antibodies specific for rat relaxin. IV. Passive immunization with monoclonal antibodies during the antepartum period reduces cervical growth and extensibility, disrupts birth, and reduces pup survival in intact rats.  Endocrinology. 1989;  125(1) 260-266
  • 46 Guico-Lamm M L, Sherwood O D. Monoclonal antibodies specific for rat relaxin. II. Passive immunization with monoclonal antibodies throughout the second half of pregnancy disrupts birth in intact rats.  Endocrinology. 1988;  123(5) 2479-2485
  • 47 Leppi T J. A study of the uterine cervix of the mouse.  Anat Rec. 1964;  150 51-65
  • 48 Kroc R L, Steinetz B G, Beach V L. The effects of estrogens, progestagens, and relaxin in pregnant and nonpregnant laboratory rodents.  Ann NY Acad Sci. 1959;  75 942-980
  • 49 Cullen B M, Harkness R D. The effect of hormones on the physical properties and collagen content of the rat's uterine cervix.  J Physiol. 1960;  152 419-436
  • 50 Zarrow M X, Neher G M, Sikes D, Brennan D M, Bullard J F. Dilatation of the uterine cervix of the sow following treatment with relaxin.  Am J Obstet Gynecol. 1956;  72(2) 260-264
  • 51 Winn R J, Baker M D, Sherwood O D. Individual and combined effects of relaxin, estrogen, and progesterone in ovariectomized gilts. I. Effects on the growth, softening, and histological properties of the cervix.  Endocrinology. 1994;  135(3) 1241-1249
  • 52 Burger L L, Sherwood O D. Relaxin increases the accumulation of new epithelial and stromal cells in the rat cervix during the second half of pregnancy.  Endocrinology. 1998;  139(9) 3984-3995
  • 53 Burger L L, Sherwood O D. Evidence that cellular proliferation contributes to relaxin-induced growth of both the vagina and the cervix in the pregnant rat.  Endocrinology. 1995;  136(11) 4820-4826
  • 54 Parry L J, McGuane J T, Gehring H M, Kostic I G, Siebel A L. Mechanisms of relaxin action in the reproductive tract: studies in the relaxin-deficient (Rlx - / - ) mouse.  Ann NY Acad Sci. 2005;  1041 91-103
  • 55 Bishop E H. Pelvic scoring for elective induction.  Obstet Gynecol. 1964;  24 266-268
  • 56 Winkler M, Rath W. Changes in the cervical extracellular matrix during pregnancy and parturition.  J Perinat Med. 1999;  27(1) 45-60
  • 57 Ludmir J, Schdev H M. Anatomy and physiology of the uterine cervix.  Clin Obstet Gynecol. 2000;  43(3) 433-439
  • 58 Westergren-Thorsson G, Norman M, Bjornsson S et al.. Differential expressions of mRNA for proteoglycans, collagens and transforming growth factor-[beta] in the human cervix during pregnancy and involution.  Biochim Biophys Acta. 1998;  1406(2) 203-213
  • 59 Leppert P C. Anatomy and physiology of cervical ripening.  Clin Obstet Gynecol. 1995;  38(2) 267-279
  • 60 Straach K J, Shelton J M, Richardson J A, Hascall V C, Mahendroo M S. Regulation of hyaluronan expression during cervical ripening.  Glycobiology. 2005;  15(1) 55-65
  • 61 Uchiyama T, Matsumoto T, Suzuki Y, Ishida M, Obara T, Kanayama T. Endogenous hyaluronan: a cytokine-like factor present in rabbit uterine cervix during pregnancy.  Biol Pharm Bull. 2004;  27(12) 1907-1912
  • 62 Obara M, Hirano H, Ogawa M et al.. Changes in molecular weight of hyaluronan and hyaluronidase activity in uterine cervical mucus in cervical ripening.  Acta Obstet Gynecol Scand. 2001;  80(6) 492-496
  • 63 Buhimschi I A, Dussably L, Buhimschi C S, Ahmed A, Weiner C P. Physical and biomechanical characteristics of rat cervical ripening are not consistent with increased collagenase activity.  Am J Obstet Gynecol. 2004;  191(5) 1695-1704
  • 64 Imada K, Sato T, Hashizume K, Tanimoto A, Sasaguri Y, Ito A. An antiprogesterone, onapristone, enhances the gene expression of promatrix metalloproteinase 3/prostromelysin-1 in the uterine cervix of pregnant rabbit.  Biol Pharm Bull. 2002;  25(9) 1223-1227
  • 65 Lyons C A, Beharry K D, Nishihara K C et al.. Regulation of matrix metalloproteinases (type IV collagenases) and their inhibitors in the virgin, timed pregnant, and postpartum rat uterus and cervix by prostaglandin E(2)-cyclic adenosine monophosphate.  Am J Obstet Gynecol. 2002;  187(1) 202-208
  • 66 Timmons B C, Mahendroo M S. Timing of neutrophil activation and expression of proinflammatory markers do not support a role for neutrophils in cervical ripening in the mouse.  Biol Reprod. 2006;  74(2) 236-245
  • 67 Sakamoto Y, Moran P, Bulmer J N, Searle R F, Robson S C. Macrophages and not granulocytes are involved in cervical ripening.  J Reprod Immunol. 2005;  66(2) 161-173
  • 68 Mackler A M, Iezza G, Akin M R, McMillan P, Yellon S M. Macrophage trafficking in the uterus and cervix precedes parturition in the mouse.  Biol Reprod. 1999;  61(4) 879-883
  • 69 Osmers R, Rath W, Adelmann-Grill B C et al.. Origin of cervical collagenase during parturition.  Am J Obstet Gynecol. 1992;  166(5) 1455-1460
  • 70 Sakamoto Y, Moran P, Searle R F, Bulmer J N, Robson S C. Interleukin-8 is involved in cervical dilatation but not in prelabour cervical ripening.  Clin Exp Immunol. 2004;  138(1) 151-157
  • 71 Sennstrom M K, Brauner A, Lu Y, Granstrom L M, Malmstrom A L, Ekman G E. Interleukin-8 is a mediator of the final cervical ripening in humans.  Eur J Obstet Gynecol Reprod Biol. 1997;  74(1) 89-92
  • 72 Roth J, Vogl T, Sorg C, Sunderkotter C. Phagocyte-specific S100 proteins: a novel group of proinflammatory molecules.  Trends Immunol. 2003;  24(4) 155-158
  • 73 Newton R A, Hogg N. The human S100 protein MRP-14 is a novel activator of the B2 integrin Mac-1 on neutrophils.  J Immunol. 1998;  160(3) 1427-1435
  • 74 Gravett M G, Novy M J, Rosenfeld R G et al.. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers.  JAMA. 2004;  292(4) 462-469
  • 75 Buhimschi I A, Christner R, Buhimschi C S. Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation.  BJOG. 2005;  112(2) 173-181
  • 76 Ruetschi U, Rosen A, Karlsson G et al.. Proteomic analysis using protein chips to detect biomarkers in cervical and amniotic fluid in women with intra-amniotic inflammation.  J Proteome Res. 2005;  4(6) 2236-2242
  • 77 Uldbjerg N, Ekman G, Malmstrom A, Ulmsten U, Wingerup L. Biochemical changes in human cervical connective tissue after local application of prostaglandin E2.  Gynecol Obstet Invest. 1983;  15(5) 291-299
  • 78 Rath W, Osmers R, Adelmann-Grill B, Stuhlsatz H, Szevereny M, Kuhn W. Biochemical changes in human cervical connective tissue after intracervical application of prostaglandin E2.  Prostaglandins. 1993;  45(4) 375-384
  • 79 Fittkow C T, Maul H, Olson G et al.. Light-induced fluorescence of the human cervix decreases after prostaglandin application for induction of labor at term.  Eur J Obstet Gynecol Reprod Biol. 2005;  123(1) 62-66
  • 80 Denison F C, Calder A A, Kelly R W. The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor.  Am J Obstet Gynecol. 1999;  180(3 Pt 1) 614-620
  • 81 Kavanagh J, Kelly A J, Thomas J. Sexual intercourse for cervical ripening and induction of labour.  Cochrane Database Syst Rev. 2001;  (2) CD003093
  • 82 Platz-Christensen J J, Pernevi P, Bokstrom H, Wiqvist N. Prostaglandin E and F2 alpha concentration in the cervical mucus and mechanism of cervical ripening.  Prostaglandins. 1997;  53(4) 253-261
  • 83 Toth M, Rehnstrom J, Fuchs A R. Prostaglandins E and F in cervical mucus of pregnant women.  Am J Perinatol. 1989;  6(2) 142-144
  • 84 Chien E K, Macgregor C. Expression and regulation of the rat prostaglandin E2 receptor type 4 (EP4) in pregnant cervical tissue.  Am J Obstet Gynecol. 2003;  189(5) 1501-1510
  • 85 Smith G C, Baguma-Nibasheka M, Wu W X, Nathanielsz P W. Regional variations in contractile responses to prostaglandins and prostanoid receptor messenger ribonucleic acid in pregnant baboon uterus.  Am J Obstet Gynecol. 1998;  179(6 pt 1) 1545-1552
  • 86 Feltovich H, Ji H, Janowski J W, Delance N C, Moran C C, Chien E K. Effects of selective and nonselective PGE2 receptor agonists on cervical tensile strength and collagen organization and microstructure in the pregnant rat at term.  Am J Obstet Gynecol. 2005;  192(3) 753-760
  • 87 Smith G C, Wu W X, Nathanielsz P W. Effects of gestational age and labor on the expression of prostanoid receptor genes in pregnant baboon cervix.  Prostaglandins Other Lipid Mediat. 2001;  63(4) 153-163
  • 88 Tornblom S A, Patel F A, Bystrom B et al.. 15-hydroxyprostaglandin dehydrogenase and cyclooxygenase 2 messenger ribonucleic acid expression and immunohistochemical localization in human cervical tissue during term and preterm labor.  J Clin Endocrinol Metab. 2004;  89(6) 2909-2915
  • 89 Gardner M O, Owen J, Skelly S, Hauth J C. Preterm delivery after indomethacin. A risk factor for neonatal complications?.  J Reprod Med. 1996;  41(12) 903-906
  • 90 Ruiz R J, Fullerton J, Dudley D J. The interrelationship of maternal stress, endocrine factors and inflammation on gestational length.  Obstet Gynecol Surv. 2003;  58(6) 415-428
  • 91 Mohan A R, Loudon J A, Bennett P R. Molecular and biochemical mechanisms of preterm labour.  Semin Fetal Neonatal Med. 2004;  9(6) 437-444
  • 92 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(1) 74-92
  • 93 Stjernholm Y, Sahlin L, Akerberg S et al.. Cervical ripening in humans: potential roles of estrogen, progesterone, and insulin-like growth factor-I.  Am J Obstet Gynecol. 1996;  174(3) 1065-1071
  • 94 Ekman-Ordeberg G, Stjernholm Y, Wang H, Stygar D, Sahlin L. Endocrine regulation of cervical ripening in humans-potential roles for gonadal steroids and insulin-like growth factor-I.  Steroids. 2003;  68 837-847
  • 95 Leppert P C. Anatomy and physiology of cervical ripening.  Clin Obstet Gynecol. 1995;  38(2) 267-279
  • 96 Alexandrova M, Soloff M S. Oxytocin receptors and parturition. I. Control of oxytocin receptor concentration in the rat myometrium at term.  Endocrinology. 1980;  106(3) 730-735
  • 97 Strauss III J F, Sokoloski J, Caploe P, Duffy P, Mintz G, Stambaugh R L. On the role of prostaglandins in parturition in the rat.  Endocrinology. 1975;  96(4) 1040-1043
  • 98 Virgo B B, Bellward G D. Serum progesterone levels in the pregnant and postpartum laboratory mouse.  Endocrinology. 1974;  95(5) 1486-1490
  • 99 Minjarez D, Konda V, Word R A. Regulation of uterine 5 alpha-reductase type 1 in mice.  Biol Reprod. 2001;  65(5) 1378-1382
  • 100 Elliott C L, Brennand J E, Calder A A. The effects of mifepristone on cervical ripening and labor induction in primigravidae.  Obstet Gynecol. 1998;  92(5) 804-809
  • 101 Stenlund P M, Ekman G, Aedo A R, Bygdeman M. Induction of labor with mifepristone-a randomized, double-blind study versus placebo.  Acta Obstet Gynecol Scand. 1999;  78(9) 793-798
  • 102 Giacalone P L, Daures J P, Faure J M, Boulot P, Hedon B, Laffargue F. The effects of mifepristone on uterine sensitivity to oxytocin and on fetal heart rate patterns.  Eur J Obstet Gynecol Reprod Biol. 2001;  97(1) 30-34
  • 103 Bygdeman M, Gemzell Danielsson K, Marions L, Swahn M. Pregnancy termination.  Steroids. 2000;  65(10-11) 801-805
  • 104 Clark K, Ji H, Feltovich H, Janowski J, Carroll C, Chien E. Mifepristone-induced cervical ripening: structural, biomechanical, and molecular events.  Am J Obstet Gynecol. 2006;  194(5) 1391-1398
  • 105 Hegele-Hartung C, Chwalisz K, Beier H M, Elger W. Ripening of the uterine cervix of the guinea-pig after treatment with the progesterone antagonist onapristone (ZK 98.299): an electron microscopic study.  Hum Reprod. 1989;  4(4) 369-377
  • 106 Wolf J P, Sinosich M, Anderson T L, Ulmann A, Baulieu E E, Hodgen G D. Progesterone antagonist (RU 486) for cervical dilation, labor induction, and delivery in monkeys: effectiveness in combination with oxytocin.  Am J Obstet Gynecol. 1989;  160(1) 45-47
  • 107 Chwalisz K, Hegele-Hartung C, Schulz R, Shi S-Q, Louton P T, Elger W. Cervical Physiology in Pregnancy and Labor. Ithaca, NY; Perinatology Press 1991
  • 108 Bukowski R, Scholz P, Hasan S H, Chwalisz K. Induction of preterm parturition with the interleukin-1beta, tumor necrosis factor alpha, and with LPS in guinea pigs.  Proc Soc Gynecol Invest. 1993;  (Suppl) S26(Abst)
  • 109 Maul H, Shi L, Marx S, Baier P, Garfield R E, Saade G R. Platelet-activating factor antagonist WEB-2170 inhibits lipopolysaccharide-induced, but not antiprogestin-induced preterm cervical ripening in timed-pregnant rats.  Am J Obset Gynecol. 2003;  189 963-967
  • 110 Deng D, Keller P K, Lo J, Word R A. Estrogen and progesterone receptor isoform distribution in cervical stroma during human pregnancy.  J Soc Gynecol Investig. 2003;  10(2) 256
  • 111 Stygar D, Wang H, Vladic Y S, Ekman G, Eriksson H, Sahlin L. Co-localization of oestrogen receptor {beta} and leukocyte markers in the human cervix.  Mol Hum Reprod. 2001;  7(9) 881-886
  • 112 Wang H, Stjernholm Y, Ekman G, Eriksson H, Sahlin L. Different regulation of oestrogen receptors {alpha} and {beta} in the human cervix at term pregnancy.  Mol Hum Reprod. 2001;  7(3) 293-300
  • 113 Madsen G, Zakar T, Ku C Y, Sanborn B M, Smith R, Mesiano S. Prostaglandins differentially modulate progesterone receptor-A and -B expression in human myometrial cells: evidence for prostaglandin-induced functional progesterone withdrawal.  J Clin Endocrinol Metab. 2004;  89(2) 1010-1013

R. Ann WordM.D. 

Professor of Obstetrics & Gynecology, Divisions of Reproductive Endocrinology and Urogynecology, University of Texas Southwestern Medical Center

5323 Harry Hines Blvd., Dallas, TX 75390-9032

Email: Ruth.Word@UTSouthwestern.edu

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