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Semin Thromb Hemost 2007; 33(1): 111-117
DOI: 10.1055/s-2006-958469
Copyright © 2007 by Thieme Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

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
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Publikationsdatum:
23. Januar 2007 (online)

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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

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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