Preterm delivery (PTD) has been associated with inflammation along with activation of the coagulation pathway. These studies sought to characterize the expression of several coagulation pathway genes including plasminogen activator inhibitor 1 (PAI-1), tissue factor (TF), protease-activated receptor 1 (Par1), protease-activated receptor 2 (Par2), fibrinogen-like protein 2 (Fgl2), and thrombomodulin (TM) during lipopolysaccharide (LPS)-induced PTD in day 15 pregnant CD-1 mice. Western blot studies confirmed protein expression for PAI-1, Par1, Par2, Fgl2, and TM in the mouse uterus. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) confirmed increased PAI-1 messenger RNA (mRNA) in the uteri, lung, kidney, and liver tissues at 2 to 6 hours after LPS injection. In contrast, TF expression significantly decreased by 12 hours in uterine tissue; whereas, its expression was unchanged in the other maternal tissues. The uterine mRNA for Par1, Par2, Fgl2, and TM remained stable. In summary, these studies have confirmed expression of coagulation pathway genes within the pregnant uterus; some of which are modulated during LPS-induced PTD.
CallaghanWMMacDormanMFRasmussenSAQinCLackritzEM. The contribution of preterm birth to infant mortality rates in the United States. Pediatrics. 2006;118(4):1566–1573.
2.
PetrouS. The economic consequences of preterm birth during the first 10 years of life. Bjog. 2005;112(suppl 1):10–15.
3.
HirschEWangH. The molecular pathophysiology of bacterially induced preterm labor: insights from the murine model. J Soc Gynecol Investig. 2005;12(3):145–155.
4.
ElovitzMAWangZChienEKRychlikDFPhillippeM. A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4. Am J Pathol. 2003; 163(5):2103–2111.
5.
TornblomSAKlimaviciuteABystromBChromekMBraunerAEkman-OrdebergG. 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.
6.
GravettMGHittiJHessDLEschenbachDA. Intrauterine infection and preterm delivery: evidence for activation of the fetal hypothalamic-pituitary-adrenal axis. Am J Obstet Gynecol. 2000;182(6):1404–1413.
7.
GravettMGWitkinSSHaluskaGJEdwardsJLCookMJNovyMJ. An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171(6):1660–1667.
8.
LeslieKKLeeSLWoodcockSM. Acute intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines in the pregnant rabbit. Am J Reprod Immunol. 2000;43(5):305–311.
9.
MussalliGMBrunnertSRHirschE. Preterm delivery in mice with renal abscess. Obstet Gynecol. 2000;95(3):453–456.
10.
RenckensRPaterJMvan der PollT. Plasminogen activator inhibitor type-1-deficient mice have an enhanced IFN-gamma response to lipopolysaccharide and staphylococcal enterotoxin B. J Immunol. 2006;177(11):8171–8176.
11.
ThibeaultILaflammeNRivestS. Regulation of the gene encoding the monocyte chemoattractant protein 1 (MCP-1) in the mouse and rat brain in response to circulating LPS and proinflammatory cytokines. J Comp Neurol. 2001;434(4):461–477.
12.
SunSZhangHXueB. Protective effect of glutathione against lipopolysaccharide-induced inflammation and mortality in rats. Inflamm Res. 2006;55(11):504–510.
13.
MorelloSVelleccoVRoviezzoF. A protective role for proteinase activated receptor 2 in airways of lipopolysaccharide-treated rats. Biochem Pharmacol. 2005;71(1-2):223–230.
14.
SteinerAALiSLlanosQJBlatteisCM. Differential inhibition by nimesulide of the early and late phases of intravenous- and intracerebroventricular-LPS-induced fever in guinea pigs. Neuroimmunomodulation. 2001;9(5):263–275.
15.
KabaroffLCRodriguezAQuintonMBoermansHKarrowNA. Assessment of the ovine acute phase response and hepatic gene expression in response to Escherichia coli endotoxin. Vet Immunol Immunopathol. 2006;113(1-2):113–124.
16.
MarisNAde VosAFBresserP. Activation of coagulation and inhibition of fibrinolysis in the lung after inhalation of lipopolysaccharide by healthy volunteers. Thromb Haemost. 2005;93(6):1036–1040.
17.
SalminenAPaananenRVuolteenahoR. Maternal endotoxin-induced preterm birth in mice: fetal responses in toll-like receptors, collectins, and cytokines. Pediatr Res. 2008;63(3):280–286.
18.
DiamondAKSweetLMOppenheimerKHBradleyDFPhillippeM. Modulation of monocyte chemotactic protein-1 expression during lipopolysaccharide-induced preterm delivery in the pregnant mouse. Reprod Sci. 2007;14(6):548–559.
19.
ChaouatG. Synergy of lipopolysaccharide and inflammatory cytokines in murine pregnancy: alloimmunization prevents abortion but does not affect the induction of preterm delivery. Cell Immunol. 1994;157(2):328–340.
20.
MitsuhashiYOtsukiKYodaAShimizuYSaitoHYanaiharaT. Effect of lactoferrin on lipopolysaccharide (LPS) induced preterm delivery in mice. Acta Obstet Gynecol Scand. 2000;79(5):355–358.
21.
EsmonCT. The interactions between inflammation and coagulation. Br J Haematol. 2005;131(4):417–430.
22.
StrukovaS. Blood coagulation-dependent inflammation. Coagulation-dependent inflammation and inflammation-dependent thrombosis. Front Biosci. 2006;11:59–80.
23.
LeviMKellerTTvan GorpEten CateH. Infection and inflammation and the coagulation system. Cardiovasc Res. 2003;60(1):26–39.
24.
BiemondBJLeviMTen CateH. Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades. Clin Sci (Lond). 1995;88(5):587–594.
25.
DeventerSJvanBullerHRCateJWtenAardenLAHackCESturkA. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood. 1990;76(12):2520–2526.
26.
DellasCLoskutoffDJ. Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. Thromb Haemost. 2005;93(4):631–640.
PhillippeMBradleyDFPhillippeKEngleD. Tissue prothrombinase activity in myometrium from timed-pregnant rats. J Soc Gynecol Investig. 2006;13(7):477–482.
29.
PawlinskiRMackmanN. Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsis. Crit Care Med. 2004;32(5 suppl):S293–S297.
30.
ZeerlederSSchroederVHackCEKohlerHPWuilleminWA. TAFI and PAI-1 levels in human sepsis. Thromb Res. 2006;118(2):205–212.
31.
DengGCurridenSAWangSRosenbergSLoskutoffDJ. Is plasminogen activator inhibitor-1 the molecular switch that governs urokinase receptor-mediated cell adhesion and release?. J Cell Biol. 1996;134(6):1563–1571.
32.
TanjungMTSiddikHDHarimanHKohSC. Coagulation and fibrinolysis in preeclampsia and neonates. Clin Appl Thromb Hemost. 2005;11(4):467–473.
33.
CoolmanMde GrootCJSteegersEA. Concentrations of plasminogen activators and their inhibitors in blood preconceptionally, during and after pregnancy. Eur J Obstet Gynecol Reprod Biol. 2006;128(1-2):22–28.
34.
KruithofEKTran-ThangCGudinchetA. Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors. Blood. 1987;69(2):460–466.
35.
GlueckCJKupfermincMJFontaineRNWangPWekslerBBEldorA. Genetic hypofibrinolysis in complicated pregnancies. Obstet Gynecol. 2001;97(1):44–48.
36.
ElovitzMABaronJPhillippeM. The role of thrombin in preterm parturition. Am J Obstet Gynecol. 2001;185(5):1059–1063.
37.
ChaiworapongsaTEspinozaJYoshimatsuJ. Activation of coagulation system in preterm labor and preterm premature rupture of membranes. J Matern Fetal Neonatal Med. 2002;11(6):368–373.
38.
RosenTKuczynskiEO'NeillLMFunaiEFLockwoodCJ. Plasma levels of thrombin-antithrombin complexes predict preterm premature rupture of the fetal membranes. J Matern Fetal Med. 2001;10(5):297–300.
39.
ChienEKSweetLPhillippeM. Protease-activated receptor isoform expression in pregnant and nonpregnant rat myometrial tissue. J Soc Gynecol Investig. 2003;10(8):460–468.
40.
FidelPIJrRomeroRMaymonEHertelendyF. Bacteria-induced or bacterial product-induced preterm parturition in mice and rabbits is preceded by a significant fall in serum progesterone concentrations. J Matern Fetal Med. 1998;7(5):222–226.
41.
ElovitzMWangZ. Medroxyprogesterone acetate, but not progesterone, protects against inflammation-induced parturition and intrauterine fetal demise. Am J Obstet Gynecol. 2004;190(3):693–701.
42.
HirschEMuhleR. Intrauterine bacterial inoculation induces labor in the mouse by mechanisms other than progesterone withdrawal. Biol Reprod. 2002;67(4):1337–1341.
