The Role of Decidualization in Regulating Endometrial Hemostasis during the Menstrual Cycle, Gestation, and in Pathological States

Charles J. Lockwood; Graciela Krikun; Mizanur Rahman; Rebeca Caze; Lynn Buchwalder; Frederick Schatz

doi:10.1055/s-2006-958469

Seminars in Thrombosis and Hemostasis, Inhaltsverzeichnis

Semin Thromb Hemost 2007; 33(1): 111-117
DOI: 10.1055/s-2006-958469

The Role of Decidualization in Regulating Endometrial Hemostasis during the Menstrual Cycle, Gestation, and in Pathological States

Charles J. Lockwood¹ , Graciela Krikun¹ , Mizanur Rahman¹ , Rebeca Caze¹ , Lynn Buchwalder¹ , Frederick Schatz¹

¹Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut

Abstract

ABSTRACT

Progesterone-induced decidualized human endometrial stromal cells form a hemostatic envelope that protects against hemorrhage during invasion of endometrial capillaries by implanting blastocyst-derived cytotrophoblasts (CTs). This hemostatic milieu reflects co-upregulated expression of tissue factor (TF), the primary initiator of hemostasis via thrombin generation and plasminogen activator inhibitor type 1, which inactivates tissue-type plasminogen activator, the primary fibrinolytic agent. During deep invasion of the decidua, CTs breach and remodel spiral arteries and arterioles to produce high-conductance vessels. Shallow invasion results in incomplete vascular transformation and an underperfused fetal-placental unit associated with preeclampsia and intrauterine growth restriction. Decidual hemorrhage and severe thrombophilias elicit aberrant thrombin generation from decidual cell-expressed TF. Such thrombin induces decidual cells to synthesize and secrete soluble fms-like tyrosine kinase-1 (sFlt-1), the matrix metalloproteinases MMP-1 and MMP-3, and the neutrophil chemoattractant interleukin-8. Excess sFlt-1 at the implantation site may inhibit CT invasion by altering the angiogenic factor balance. During abruptions, thrombin-enhanced MMP-1, MMP-3 by decidual cells and neutrophil-derived proteases degrade the decidual and fetal membrane extracellular matrix to promote preterm premature rupture of the membranes. In association with long-term progestin-only contraception, overexpression of decidual cell-derived thrombin promotes aberrant angiogenesis and vessel maintenance to contribute to abnormal uterine bleeding.

KEYWORDS

Tissue factor - plasminogen activator inhibitor type 1 - decidua - abruption

Volltext

Referenzen

REFERENCES

1 Nemerson Y. Tissue factor and hemostasis. Blood. 1988; 71 1-8
2 Drake T A, Morrissey J H, Edgington T S. Selective cellular expression of tissue factor in human tissues. Implications for disorders of hemostasis and thrombosis. Am J Pathol. 1989; 134 1087-1097
3 Tilley R, Mackman N. Tissue factor in hemostasis and thrombosis. Semin Thromb Hemost. 2006; 32 5-10
4 Mignatti P, Rifkin D B. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev. 1993; 73 161-195
5 Tabanelli S, Tang B, Gurpide E. In vitro decidualization of human endometrial stromal cells. J Steroid Biochem Mol Biol. 1992; 42 337-344
6 Lockwood C J, Nemerson Y, Guller S et al.. Progestational regulation of human endometrial stromal cell tissue factor expression during decidualization. J Clin Endocrinol Metab. 1993; 76 231-236
7 Lockwood C J, Krikun G, Papp C et al.. The role of progestationally regulated stromal cell tissue factor and type-1 plasminogen activator inhibitor (PAI-1) in endometrial hemostasis and menstruation. Ann NY Acad Sci. 1994; 734 57-79
8 Lockwood C J, Krikun G, Papp C et al.. Biological mechanisms underlying RU 486 clinical effects: inhibition of endometrial stromal cell tissue factor content. J Clin Endocrinol Metab. 1994; 79 786-790
9 Schatz F, Aigner S, Papp C et al.. Plasminogen activator activity during decidualization of human endometrial stromal cells is regulated by plasminogen activator inhibitor 1. J Clin Endocrinol Metab. 1995; 80 2504-2510
10 Irwin J C, Kirk D, King R JB et al.. Hormonal regulation of human endometrial stromal cells in culture: an in vitro model for decidualization. Fertil Steril. 1989; 52 761-768
11 Schatz F, Krikun G, Caze R et al.. Progestin-regulated expression of tissue factor in decidual cells: implications in endometrial hemostasis, menstruation and angiogenesis. Steroids. 2003; 68 849-860
12 Mackman N. Regulation of the tissue factor gene. Thromb Haemost. 1997; 78 747-754
13 Krikun G, Schatz F, Mackman N et al.. Regulation of tissue factor gene expression in human endometrium by transcription factors Sp1 and Sp3. Mol Endocrinol. 2000; 14 393-400
14 Moore K L. The Developing Human. 4th ed. Philadelphia, PA; W.B. Saunders 1988
15 Oka C, Makino T, Itakura I et al.. Chemical abortion in patients with recurrent fetal loss. Nippon Sanka Fujinka Gakkai Zasshi. 1991; 43 239-240
16 Ramsey E M, Houston M L, Harris J W. Interactions of the trophoblast and maternal tissues in three closely related primate species. Am J Obstet Gynecol. 1976; 124 645-647
17 Brosens J J, Pijnenborg R, Brosens I A. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol. 2002; 187 1416-1423
18 Edmonds D K, Lindsay K S, Miller J F et al.. Early embryonic mortality in women. Fertil Steril. 1982; 38 447-453
19 Coughlin S R. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost. 2005; 3 1800-1814
20 Runic R, Schatz F, Wan L et al.. Effects of Norplant on endometrial tissue factor expression and blood vessel structure. J Clin Endocrinol Metab. 2000; 85 3853-3859
21 Hickey M, Carati F, Manconi B J et al.. The measurement of endometrial perfusion in Norplant users: a pilot study. Hum Reprod. 2000; 15 1086-1091
22 Krikun G, Critchley H, Schatz F et al.. Abnormal uterine bleeding during progestin-only contraception may result from free radical-induced alterations in angiopoietin expression. Am J Pathol. 2002; 161 979-986
23 Lockwood C J, Krikun G, Koo A B et al.. Differential effects of thrombin and hypoxia on endometrial stromal and glandular epithelial cell vascular endothelial growth factor expression. J Clin Endocrinol Metab. 2002; 87 4280-4286
24 Lockwood C J, Kumar P, Krikun G et al.. Effects of thrombin, hypoxia, and steroids on interleukin-8 expression in decidualized human endometrial stromal cells: implications for long-term progestin-only contraceptive-induced bleeding. J Clin Endocrinol Metab. 2004; 89 1467-1475
25 Ferrara N. Molecular and biological properties of vascular endothelial growth factor. J Mol Med. 1999; 77 527-543
26 Strieter R M, Kunkel S L, Elner V M. Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol. 1992; 141 1279-1284
27 Di Paolo S, Volpe P, Grandaliano G et al.. Increased placental expression of tissue factor is associated with abnormal uterine and umbilical Doppler waveforms in severe preeclampsia with fetal growth restriction. J Nephrol. 2003; 16 650-657
28 Schatz F, Toti P, Arcuri F et al.. Thrombin regulates expression of soluble fms-like tyrosine kinase-1 in first trimester decidual cells: implications for preeclampsia. Paper presented at: 53rd Annual Meeting of the Society for Gynecologic Investigation 2006 (abst 674)
29 Karumanchi S A, Bdolah Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology. 2004; 145 4835-4837
30 Roberts J M, Gammill H S. Preeclampsia: recent insights. Hypertension. 2005; 46 1243-1249
31 Lockwood C J, Toti P, Arcuri F et al.. Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin-enhanced interleukin-8 expression in term decidua. Am J Pathol. 2005; 167 1443-1449
32 Malak T M, Ockleford C D, Bell S C et al.. Confocal immunofluorescence localization of collagen types I, III, IV, V and VI and their ultrastructural organization in term human fetal membranes. Placenta. 1993; 14 385-406
33 Maragoudakis M E, Tsopanoglou N E, Andriopoulou P. Mechanism of thrombin-induced angiogenesis. Biochem Soc Trans. 2002; 30 173-177
34 Rosen T, Schatz F, Kuczynski E et al.. Thrombin-enhanced matrix metalloproteinase-1 expression: a mechanism linking placental abruption with premature rupture of the membranes. J Matern Fetal Neonatal Med. 2002; 11 11-17
35 Mackenzie A P, Schatz F, Krikun G et al.. Mechanisms of abruption-induced premature rupture of the fetal membranes: thrombin enhanced decidual matrix metalloproteinase-3 (stromelysin-1) expression. Am J Obstet Gynecol. 2004; 191 1996-2001
36 Birkedal-Hansen H, Moore W G, Bodden M K et al.. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med. 1993; 4 197-250
37 Baggiolini M. Chemokines and leukocyte traffic. Nature. 1998; 392 565-568
38 Maymon E, Romero R, Pacora P et al.. Human neutrophil collagenase (matrix metalloproteinase 8) in parturition, premature rupture of the membranes, and intrauterine infection. Am J Obstet Gynecol. 2000; 183 94-99
39 Vu T H, Werb Z. Gelatinase B: structure, regulation, and function. In: Parks WC, Mecham R Matrix Metalloproteinases. San Diego, CA; Academic Press 1998: 115-148
40 Meis P J, Klebanoff M, Thom E et al.. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003; 348 2379-2385

Frederick SchatzPh.D.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine

333 Cedar Street, Room 335 FMB, P.O. Box 208063, New Haven, CT 06511

eMail: frederick.schatz@yale.edu