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Novel insights into molecular mechanisms of abruption-induced preterm birth

Published online by Cambridge University Press:  01 November 2010

Catalin S. Buhimschi*
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Frederik Schatz
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Graciela Krikun
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Irina A. Buhimschi
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
Charles J. Lockwood
Affiliation:
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
*
*Corresponding author: Catalin S. Buhimschi, Yale University School of Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, 333 Cedar Street, LLCI 804, New Haven, CT 06520, USA. E-mail: [email protected]

Abstract

Preterm birth (PTB) complicates more than 12% of all deliveries. Despite significant research, the aetiology of most cases of PTB remains elusive. Two major antecedents of PTB, intra-amniotic infection and decidual haemorrhage (abruption), can exhibit dissimilar demographic and genetic predispositions, despite sharing common molecular and cellular pathways. The use of high-throughput, high-dimensional technologies reveals substantial crosstalk between the coagulation and inflammation pathways. Tissue factor, thrombin and cytokines are key mediators of this crosstalk. Abruptions are associated with excess thrombin generated from decidual-cell-expressed tissue factor. Although thrombin is a primary mediator of the coagulation cascade, it can also promote inflammation-associated PTB by enhancing expression of matrix metalloproteinase and neutrophil-chemoattracting and -activating chemokines. Here, we provide novel insights into the molecular mechanisms and pathways leading to PTB in the setting of placental abruption.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2010

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References

References

1Stoll, B.J. et al. (2004) National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. Journal of the American Medical Association 292, 2357-2365CrossRefGoogle Scholar
2Zerhouni, E.A. (2005) US biomedical research: basic, translational, and clinical sciences. Journal of the American Medical Association 294, 1352-1358CrossRefGoogle ScholarPubMed
3Fagnan, L.J. (2010) Linking practice-based research networks and clinical and translational science awards: new opportunities for community engagement by academic health centers. Academic Medicine 85, 476-483CrossRefGoogle ScholarPubMed
4McLean, M. et al. (1995) A placental clock controlling the length of human pregnancy. Nature Medicine 1, 460-463CrossRefGoogle ScholarPubMed
5Zenclussen, A.C. et al. (2007) Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus. Expert Reviews in Molecular Medicine 9, 1-14CrossRefGoogle ScholarPubMed
6Mendelson, C.R. (2009) Minireview: fetal–maternal hormonal signaling in pregnancy and labor. Molecular Endocrinology 23, 947-954CrossRefGoogle ScholarPubMed
7Muglia, L.J. and Katz, M. (2010) The enigma of spontaneous preterm birth. New England Journal of Medicine 362, 529-535CrossRefGoogle ScholarPubMed
8Buhimschi, C.S. et al. (2008) Multidimensional system biology: genetic markers and proteomic biomarkers of adverse pregnancy outcome in preterm birth. American Journal of Perinatology 25, 175-187CrossRefGoogle ScholarPubMed
9Lockwood, C.J. and Kuczynski, E. (2001) Risk stratification and pathological mechanisms in preterm delivery. Paediatric and Perinatal Epidemiology 2, 78-89CrossRefGoogle Scholar
10Anum, E.A. et al. (2009) Genetic contributions to disparities in preterm birth. Pediatric Research 65, 1-9CrossRefGoogle ScholarPubMed
11Challis, J.R. et al. (2009) Inflammation and pregnancy. Reproductive Sciences 16, 206-215CrossRefGoogle ScholarPubMed
12Norman, J.E. et al. (2007) Inflammatory pathways in the mechanism of parturition. BMC Pregnancy Childbirth 7 (Suppl 1), S7CrossRefGoogle ScholarPubMed
13Weiner, C.P. et al. (2010) Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor. American Journal of Obstetrics and Gynecology 202, 474.e1-474.e20CrossRefGoogle ScholarPubMed
14Hall, D.R. (2009) Abruptio placentae and disseminated intravascular coagulopathy. Seminars in Perinatology 33, 189-195CrossRefGoogle ScholarPubMed
15Elsasser, D.A. et al. (2010) Diagnosis of placental abruption: relationship between clinical and histopathological findings. European Journal of Obstetrics, Gynecology, and Reproductive Biology 148, 125-130CrossRefGoogle ScholarPubMed
16Ananth, C.V. et al. (2005) Placental abruption in the United States, 1979 through 2001: temporal trends and potential determinants. American Journal of Obstetrics and Gynecology 192, 191-198CrossRefGoogle ScholarPubMed
17Ananth, C.V. et al. (1999) Placental abruption and adverse perinatal outcomes. Journal of the American Medical Association 282, 1646-1651CrossRefGoogle ScholarPubMed
18Oyelese, Y. and Ananth, C.V. (2006) Placental abruption. Obstetrics and Gynecology 108, 1005-1016CrossRefGoogle ScholarPubMed
19Ananth, C.V. and Wilcox, A.J. (2001) Placental abruption and perinatal mortality in the United States. American Journal of Epidemiology 153, 332-337CrossRefGoogle ScholarPubMed
20Salafia, C.M. et al. (1995) Histologic evidence of old intrauterine bleeding is more frequent in prematurity. American Journal of Obstetrics and Gynecology 173, 1065-1070CrossRefGoogle ScholarPubMed
21Lockwood, C.J. (2006) Pregnancy-associated changes in the hemostatic system. Clinical Obstetrics and Gynecology 49, 836-843CrossRefGoogle ScholarPubMed
22Benirschke, K. (1994) Anatomical relationship between fetus and mother. Annals of the New York Academy of Sciences 731, 9-20CrossRefGoogle ScholarPubMed
23Dommisse, J. and Tiltman, A.J. (1992) Placental bed biopsies in placental abruption. British Journal of Obstetrics and Gynaecology 99, 651-654CrossRefGoogle ScholarPubMed
24Nath, C.A. et al. (2007) Histologic evidence of inflammation and risk of placental abruption. New Jersey-placental abruption study investigators. American Journal of Obstetrics and Gynecology 197, 319.e1-319.e6CrossRefGoogle Scholar
25Arias, F. et al. (1993) Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes. American Journal of Obstetrics and Gynecology 168, 585-591CrossRefGoogle ScholarPubMed
26Pober, J.S. and Sessa, W.C. (2007) Evolving functions of endothelial cells in inflammation. Nature Reviews. Immunology 7, 803-815Google Scholar
27Kumar, P. et al. (2009) Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Reviews in Molecular Medicine 11, e19CrossRefGoogle ScholarPubMed
28Reznik, S.E. et al. (1998) Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord. Journal of Histochemistry and Cytochemistry 46, 1359-1368CrossRefGoogle Scholar
29Liu, J. et al. (2009) Advanced glycation end products and lipopolysaccharide synergistically stimulate proinflammatory cytokine/chemokine production in endothelial cells via activation of both mitogen-activated protein kinases and nuclear factor-kappaB. FEBS Journal 276, 4598-4606CrossRefGoogle ScholarPubMed
30Pinheiro da Silva, F. and Soriano, F.G. (2009) Neutrophils recruitment during sepsis: critical points and crossroads. Frontiers in Bioscience 14, 4464-4476CrossRefGoogle ScholarPubMed
31Ley, K. and Reutershan, J. (2006) Leucocyte–endothelial interactions in health and disease. Handbook of Experimental Pharmacology 176, 97-133CrossRefGoogle Scholar
32Levi, M. and van der Poll, T. (2010) Inflammation and coagulation. Critical Care Medicine 38, S26-S34CrossRefGoogle ScholarPubMed
33Bach, R., Nemerson, Y. and Konigsberg, W. (1981) Purification and characterization of bovine tissue factor. Journal of Biological Chemistry 256, 8324-8331CrossRefGoogle ScholarPubMed
34Spicer, E.K. et al. (1987) Isolation of cDNA clones coding for human tissue factor: primary structure of the protein and cDNA. Proceedings of the National Academy of Sciences of the United States of America 84, 5148-5152CrossRefGoogle ScholarPubMed
35Polgar, J., Matuskova, J. and Wagner, D.D. (2005) The P-selectin, tissue factor, coagulation triad. Journal of Thrombosis and Haemostasis 3, 1590-1596CrossRefGoogle ScholarPubMed
36Moll, T. et al. (1995) Regulation of the tissue factor promoter in endothelial cells. Journal of Biological Chemistry 270, 3849-3857CrossRefGoogle ScholarPubMed
37Rao, L.V. and Mackman, N. (2010) Factor VIIa and tissue factor – from cell biology to animal models. Thrombosis Research 125 (Suppl 1), S1-S3CrossRefGoogle ScholarPubMed
38Popescu, N.I., Lupu, C. and Lupu, F. (2010) Role of PDI in regulating tissue factor: FVIIa activity. Thrombosis Research 125 (Suppl 1), S38-S41CrossRefGoogle ScholarPubMed
39Mackman, N. (2009) The many faces of tissue factor. Journal of Thrombosis and Haemostasis 1, 136-139CrossRefGoogle Scholar
40Krikun, G., Lockwood, C.J. and Paidas, M.J. (2009) Tissue factor and the endometrium: from physiology to pathology. Thrombosis Research 124, 393-396CrossRefGoogle ScholarPubMed
41Rao, L.V., Pendurthi, U.R. (2003) Regulation of tissue factor–factor VIIa expression on cell surfaces: a role for tissue factor–factor VIIa endocytosis. Molecular and Cellular Biochemistry 253, 131-140CrossRefGoogle ScholarPubMed
42Aharon, A. et al. (2004) Tissue factor and tissue factor pathway inhibitor levels in trophoblast cells: implications for placental hemostasis. Thrombosis and Haemostasis 92, 776-786Google ScholarPubMed
43Drake, T.A., Morrissey, J.H. and Edgington, T.S. (1989) Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. American Journal of Pathology 134, 1087-1097Google ScholarPubMed
44Stassen, J.M., Arnout, J. and Deckmyn, H. (2004) The hemostatic system. Current Medical Chemistry 11, 2245-2260CrossRefGoogle ScholarPubMed
45Lockwood, C.J. et al. (1991) Amniotic fluid contains tissue factor, a potent initiator of coagulation. American Journal of Obstetrics and Gynecology 165, 1335-1341CrossRefGoogle ScholarPubMed
46Lockwood, C.J. et al. (2009) Progestin and thrombin regulate tissue factor expression in human term decidual cells. Journal of Clinical Endocrinology and Metabolism 94, 2164-2170CrossRefGoogle ScholarPubMed
47Lockwood, C.J. et al. (1993) Progestational regulation of human endometrial stromal cell tissue factor expression during decidualization. Journal of Clinical Endocrinology and Metabolism 76, 231-236Google ScholarPubMed
48Schatz, F. et al. (2003) Progestin-regulated expression of tissue factor in decidual cells: implications in endometrial hemostasis, menstruation and angiogenesis. Steroids 68, 849-860CrossRefGoogle ScholarPubMed
49Lockwood, C.J. et al. (2000) Progestin-epidermal growth factor regulation of tissue factor expression during decidualization of human endometrial stromal cells. Journal of Clinical Endocrinology and Metabolism 85, 297-301Google ScholarPubMed
50Erlich, J. et al. (1999) Tissue factor is required for uterine hemostasis and maintenance of the placental labyrinth during gestation. Proceedings of the National Academy of Sciences of the United States of America 96, 8138-8143CrossRefGoogle ScholarPubMed
51Bergh, N. et al. (2009) Influence of TNF-alpha and biomechanical stress on endothelial anti- and prothrombotic genes. Biochemical and Biophysical Research Communications 385, 314-318CrossRefGoogle ScholarPubMed
52Mertens, G. et al. (1992) Cell surface heparan sulfate proteoglycans from human vascular endothelial cells. Core protein characterization and antithrombin III binding properties. Journal of Biological Chemistry 267, 20435-20443CrossRefGoogle ScholarPubMed
53Jackson, C.J. and Xue, M. (2008) Activated protein C – an anticoagulant that does more than stop clots. International Journal of Biochemistry and Cell Biology 40, 2692-2697CrossRefGoogle ScholarPubMed
54Castellino, F.J. and Ploplis, V.A. (2009) The protein C pathway and pathologic processes. Journal of Thrombosis and Haemostasis 7 (Suppl 1), 140-145CrossRefGoogle ScholarPubMed
55Ignarro, L.J. (1989) Endothelium-derived nitric oxide: actions and properties. FASEB Journal 3, 31-36CrossRefGoogle ScholarPubMed
56Harris, L.K. (2008) Trophoblast-derived heparanase is not required for invasion. Placenta 29, 332-337CrossRefGoogle Scholar
57Dempsey, L.A. et al. (2000) Heparanase expression in invasive trophoblasts and acute vascular damage. Glycobiology 10, 467-475CrossRefGoogle ScholarPubMed
58Meeusen, E.N., Bischof, R.J. and Lee, C.S. (2001) Comparative T-cell responses during pregnancy in large animals and humans. American Journal of Reproductive Immunology 46, 169-179CrossRefGoogle Scholar
59Martinon, F., Mayor, A. and Tschopp, J. (2009) The inflammasomes: guardians of the body. Annual Review of Immunology 27, 229-265CrossRefGoogle ScholarPubMed
60Reddy, R.C. et al. (2001) Sepsis-induced immunosuppression: from bad to worse. Immunologic Research 24, 273-287CrossRefGoogle ScholarPubMed
61Cinel, I. and Opal, S.M. (2009) Molecular biology of inflammation and sepsis: a primer. Critical Care Medicine 37, 291-304CrossRefGoogle Scholar
62Benhamou, Y. et al. (2009) Toll-like receptors 4 contribute to endothelial injury and inflammation in hemorrhagic shock in mice. Critical Care Medicine 37, 1724-1728CrossRefGoogle ScholarPubMed
63Arcuri, F. et al. (2009) Mechanisms of leukocyte accumulation and activation in chorioamnionitis: interleukin 1 beta and tumor necrosis factor alpha enhance colony stimulating factor 2 expression in term decidua. Reproductive Sciences 16, 453-461CrossRefGoogle ScholarPubMed
64Lockwood, C.J. et al. (2008) Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells. Biology of Reproduction 78, 1064-1072CrossRefGoogle ScholarPubMed
65Buhimschi, I.A. et al. (1998) The nitric oxide pathway in pre-eclampsia: pathophysiological implications. Human Reproduction Update 4, 25-42CrossRefGoogle ScholarPubMed
66Lee, S. et al. (2008) The interleukin-6 (IL-6) trans-signaling system: evidence for presence and activation in pregnancies complicated by intra-amniotic infection. American Journal of Obstetrics and Gynecology 199, S141. Presented at the Society for Maternal Fetal Medicine 2009 (26-31 January 2009; San Diego, CA, USA)CrossRefGoogle Scholar
67Buhimschi, I.A. et al. (2007) The receptor for advanced glycation end products (RAGE) system in women with intra-amniotic infection and inflammation. American Journal of Obstetrics and Gynecology 196, e1-e13CrossRefGoogle ScholarPubMed
68Dunk, C. et al. (2000) Angiopoietin-1 and angiopoietin-2 activate trophoblast Tie-2 to promote growth and migration during placental development. American Journal of Pathology 156, 2185-2199CrossRefGoogle ScholarPubMed
69Ahmed, A. et al. (1997) Role of VEGF receptor-1 (Flt-1) in mediating calcium-dependent nitric oxide release and limiting DNA synthesis in human trophoblast cells. Laboratory Investigation 76, 779-791Google ScholarPubMed
70Holmlund, U. et al. (2007) The novel inflammatory cytokine high mobility group box protein 1 (HMGB1) is expressed by human term placenta. Immunology 122, 430-437CrossRefGoogle ScholarPubMed
71Buhimschi, C.S. et al. (2010) Amniotic fluid angiopoietin-1, angiopoietin-2, and soluble receptor Tie2 levels and regulation in normal pregnancy and intra-amniotic inflammation induced preterm birth. Journal of Clinical Endocrinology and Metabolism 95, 3428-3436CrossRefGoogle Scholar
72Bulmer, J.N., Williams, P.J. and Lash, G.E. (2010) Immune cells in the placental bed. International Journal of Developmental Biology 54, 281-294CrossRefGoogle ScholarPubMed
73Mantovani, A. et al. (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends in Immunology 25, 677-686CrossRefGoogle ScholarPubMed
74Gustafsson, C. et al. (2008) Gene expression profiling of human decidual macrophages: evidence for immunosuppressive phenotype. PLoS One 3, e2078CrossRefGoogle ScholarPubMed
75Pétrilli, V. et al. (2007) The inflammasome: a danger sensing complex triggering innate immunity. Current Opinion in Immunology 19, 615-622CrossRefGoogle ScholarPubMed
76Buhimschi, C.S. et al. (2009) Characterization of RAGE, HMGB1, and S100beta in inflammation-induced preterm birth and fetal tissue injury. American Journal of Pathology 175, 958-975CrossRefGoogle ScholarPubMed
77Kimbrell, D.A. and Beutler, B. (2001) The evolution and genetics of innate immunity. Nature Reviews. Genetics 2, 256-267Google Scholar
78Medzhitov, R. (2007) Recognition of microorganisms and activation of the immune response. Nature 449, 819-826CrossRefGoogle ScholarPubMed
79Buhimschi, I.A., Christner, R. and Buhimschi, C.S. (2005) Proteomic biomarker analysis of amniotic fluid for identification of intra-amniotic inflammation. BJOG 112, 173-181CrossRefGoogle ScholarPubMed
80Buhimschi, I.A. et al. (2008) Multidimensional proteomics analysis of amniotic fluid to provide insight into the mechanisms of idiopathic preterm birth. PLoS One 23, 3, e2049CrossRefGoogle ScholarPubMed
81Cakmak, H. et al. (2005) Progestin suppresses thrombin- and interleukin-1beta-induced interleukin-11 production in term decidual cells: implications for preterm delivery. Journal of Clinical Endocrinology and Metabolism 90, 5279-5286CrossRefGoogle ScholarPubMed
82Buhimschi, C.S. and Buhimschi, I.A. (2007) Proteomic biomarkers of adverse pregnancy outcome in preterm birth – a theranostics opportunity. Future drugs – expert review. Obstetrics and Gynecology 2, 743-753Google Scholar
83Lockwood, C.J. et al. (2005) Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua. American Journal of Pathology 167, 1443-1449CrossRefGoogle ScholarPubMed
84Krikun, G. et al. (2007) Expression of Toll-like receptors in the human decidua. Histology and Histopathology 22, 847-854Google ScholarPubMed
85Koga, K. and Mor, G. (2008) Expression and function of toll-like receptors at the maternal–fetal interface. Reproductive Sciences 15, 231-242CrossRefGoogle ScholarPubMed
86Buhimschi, C.S. et al. (2009) Insight into innate immunity of the uterine cervix as a host defense mechanism against infection and preterm birth. Expert Review of Obstetrics and Gynecology 4, 9-15CrossRefGoogle Scholar
87van Zoelen, M.A. et al. (2009) Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo. Shock 31, 280-284CrossRefGoogle ScholarPubMed
88Cohen, M.J. et al. (2009) Early release of high mobility group box nuclear protein 1 after severe trauma in humans: role of injury severity and tissue hypoperfusion. Critical Care 13, R174CrossRefGoogle ScholarPubMed
89Ananth, C.V. et al. (2004) Preterm premature rupture of membranes, intrauterine infection, and oligohydramnios: risk factors for placental abruption. Obstetrics and Gynecology 2004, 104, 71-77Google ScholarPubMed
90Lockwood, C.J. et al. (2009) Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption. Thrombosis Research 124, 516-520CrossRefGoogle ScholarPubMed
91Esmon, C.T. (2008) Crosstalk between inflammation and thrombosis. Maturitas 61, 122-131CrossRefGoogle ScholarPubMed
92Taylor, F.B. Jr. et al. (1984) A model for thrombin protection against endotoxin. Thrombosis Research 36, 177-185CrossRefGoogle Scholar
93Rosen, T. et al. (2001) Plasma levels of thrombin-antithrombin complexes predict preterm premature rupture of the fetal membranes. Journal of Maternal–Fetal and Neonatal Medicine 10, 297-300CrossRefGoogle ScholarPubMed
94Fiedler, U. and Augustin, H.G. (2006) Angiopoietins: a link between angiogenesis and inflammation. Trends in Immunology 27, 552-558CrossRefGoogle ScholarPubMed
95Krikun, G. et al. (2007) Thrombin activation of endometrial endothelial cells: a possible role in intrauterine growth restriction. Thrombosis and Haemostasis 97, 245-253Google ScholarPubMed
96Lockwood, C.J. et al. (2007) Thrombin regulates soluble fms-like tyrosine kinase-1 (sFlt-1) expression in first trimester decidua: implications for preeclampsia. American Journal of Pathology 170, 1398-1405CrossRefGoogle ScholarPubMed
97Goldman-Wohl, D. and Yagel, S. (2002) Regulation of trophoblast invasion: from normal implantation to pre-eclampsia. Molecular and Cellular Endocrinology 187, 233-238CrossRefGoogle ScholarPubMed
98Krikun, G. et al. (2004) Endometrial angiopoietin expression and modulation by thrombin and steroid hormones: a mechanism for abnormal angiogenesis following long-term progestin-only contraception. American Journal of Pathology 164, 2101-2107CrossRefGoogle ScholarPubMed
99Chaudhari, B.P. et al. (2008) The genetics of birth timing: insights into a fundamental component of human development. Clinical Genetics 74, 493-501CrossRefGoogle ScholarPubMed
100Nesin, M. (2007) Genetic basis of preterm birth. Frontiers in Bioscience 12, 115-124CrossRefGoogle ScholarPubMed
101Rasmussen, S., Irgens, L.M. and Dalaker, K. (1997) The effect on the likelihood of further pregnancy of placental abruption and the rate of its recurrence. British Journal of Obstetrics and Gynaecology 104, 1292-1295CrossRefGoogle ScholarPubMed
102Peltier, M.R. (2009) Thromboembolic diseases in families of women with placental abruption. Epidemiology 20, 733-737CrossRefGoogle ScholarPubMed
103Rasmussen, S. and Irgens, L.M. (2009) Occurrence of placental abruption in relatives. BJOG 116, 693-699CrossRefGoogle ScholarPubMed
104Kinzler, W.L. et al. (2009) The effect of maternal thrombophilia on placental abruption: histologic correlates. Journal of Maternal–Fetal and Neonatal Medicine 22, 243-248CrossRefGoogle ScholarPubMed
105van der Molen, E.F. et al. (2000) A common mutation in the 5,10-methylenetetrahydro-folate reductase gene as a new risk factor for placental vasculopathy. American Journal of Obstetrics and Gynecology 182, 1258-1263CrossRefGoogle Scholar
106Procházka, M. (2003) Factor V Leiden in pregnancies complicated by placental abruption. BJOG 110, 462-466CrossRefGoogle ScholarPubMed
107Jaaskelainen, E. et al. (2008) Polymorphism of the interleukin 1 receptor antagonist (IL1Ra) gene and placental abruption. Journal of Reproductive Immunology 79, 58-62CrossRefGoogle ScholarPubMed
108Ananth, C.V. et al. (2007) Associations between 2 polymorphisms in the methylene-tetrahydrofolate reductase gene and placental abruption. American Journal of Obstetrics and Gynecology 197, 385.e1-385.e7CrossRefGoogle ScholarPubMed
109Zdoukopoulos, N. and Zintzaras, E. (2008) Genetic risk factors for placental abruption: a HuGE review and meta-analysis. Epidemiology 19, 309-323CrossRefGoogle ScholarPubMed
110Said, J.M. et al. (2010) Inherited thrombophilia polymorphisms and pregnancy outcomes in nulliparous women. Obstetrics and Gynecology 115, 5-13CrossRefGoogle ScholarPubMed
111Silver, R.M. et al. (2010) Prothrombin gene G20210A mutation and obstetric complications. Obstetrics and Gynecology 115, 14-20CrossRefGoogle ScholarPubMed
112Anteby, E.Y. et al. (2004) Fetal inherited thrombophilias influence the severity of preeclampsia, IUGR and placental abruption. European Journal of Obstetrics, Gynecology, and Reproductive Biology 113, 31-35CrossRefGoogle ScholarPubMed
113Redline, R.W. and Pappin, A. (1995) Fetal thrombotic vasculopathy: the clinical significance of extensive avascular villi. Human Pathology 26, 80-85CrossRefGoogle ScholarPubMed
114Smith, R. (2007) Parturition. New England Journal of Medicine 356, 271-283CrossRefGoogle ScholarPubMed
115Csapo, A. (1956) Progesterone “block.” American Journal of Anatomy 98, 273-292CrossRefGoogle ScholarPubMed
116Tita, A.T. and Rouse, D.J. (2009) Progesterone for preterm birth prevention: an evolving intervention. American Journal of Obstetrics and Gynecology 200, 219-224CrossRefGoogle ScholarPubMed
117Mesiano, S. and Welsh, T.N. (2007) Steroid hormone control of myometrial contractility and parturition. Seminars in Cell and Developmental Biology 18, 321-331CrossRefGoogle ScholarPubMed
118Merlino, A. et al. (2009) Nuclear progesterone receptor expression in the human fetal membranes and decidua at term before and after labor. Reproductive Science 16, 357-363CrossRefGoogle ScholarPubMed
119Schatz, F. and Lockwood, C.J. (1993) Progestin regulation of plasminogen activator inhibitor type 1 in primary cultures of endometrial stromal and decidual cells. Journal of Clinical Endocrinology and Metabolism 77, 621-625Google ScholarPubMed
120Krikun, G. et al. (1998) Transcriptional regulation of the tissue factor gene by progestins in human endometrial stromal cells. Journal of Clinical Endocrinology and Metabolism 83, 926-930Google ScholarPubMed
121Krikun, G. et al. (2000) Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3. Molecular Endocrinology 14, 393-400CrossRefGoogle ScholarPubMed
122Norwitz, E.R. et al. (2007) Progestin inhibits and thrombin stimulates the plasminogen activator/inhibitor system in term decidual stromal cells: implications for parturition. American Journal of Obstetrics and Gynecology 196, 382.e1-382.e8CrossRefGoogle ScholarPubMed
123Lockwood, C.J. (1994) Biological mechanisms underlying RU 486 clinical effects: inhibition of endometrial stromal cell tissue factor content. Journal of Clinical Endocrinology and Metabolism 79, 786-790Google ScholarPubMed
124Lockwood, C.J. et al. (1998) Matrix metalloproteinase and matrix metalloproteinase inhibitor expression in endometrial stromal cells during progestin-initiated decidualization and menstruation-related progestin withdrawal. Endocrinology 139, 4607-4613CrossRefGoogle ScholarPubMed
125Schatz, F. et al. (1999) Implications of decidualization-associated protease expression in implantation and menstruation. Seminars in Reproductive Endocrinology 17, 3-12CrossRefGoogle ScholarPubMed
126Christiaens, I. et al. (2008) Inflammatory processes in preterm and term parturition. Journal of Reproductive Immunology 79, 50-57CrossRefGoogle ScholarPubMed
127Trepicchio, W.L. et al. (1996) Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. Journal of Immunology 157, 3627-3634CrossRefGoogle ScholarPubMed
128Anum, E.A. et al. (2009) Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity. Placenta 30, 207-215CrossRefGoogle ScholarPubMed
129Parry, S., Strauss, J.F. III (1998) Premature rupture of the fetal membranes. New England Journal of Medicine 338, 663-670CrossRefGoogle ScholarPubMed
130Rosen, T. et al. (2002) Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes. Journal of Maternal–Fetal and Neonatal Medicine 11, 11-17CrossRefGoogle ScholarPubMed
131Stephenson, C.D. et al. (2005) Thrombin-dependent regulation of matrix metalloproteinase (MMP)-9 levels in human fetal membranes. Journal of Maternal–Fetal and Neonatal Medicine 18, 17-22CrossRefGoogle ScholarPubMed
132Buhimschi, I.A. et al. (2000) Reduction–oxidation (redox) state regulation of matrix metalloproteinase activity in human fetal membranes. American Journal of Obstetrics and Gynecology 182, 458-464CrossRefGoogle ScholarPubMed

Further reading, resources and contacts

The International HapMap Project is a partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the U.S.A. to develop a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals. For more information, consulthttp://hapmap.ncbi.nlm.nih.gov/abouthapmap.htmlGoogle Scholar
Online Mendelian Inheritance in Man is a comprehensive compendium of human genes and genetic phenotypes. Information regarding the F5 gene, which encodes coagulation factor V and the 20210G-A mutation in the prothrombin F2 gene, can be found athttp://www.ncbi.nlm.nih.gov/omimGoogle Scholar