The role of decidualization in regulating endometrial hemostasis during the menstrual cycle, gestation, and in pathological states.
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.
Lockwood
Charles J
CJ
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06511, USA.
Krikun
Graciela
G
Rahman
Mizanur
M
Caze
Rebeca
R
Buchwalder
Lynn
L
Schatz
Frederick
F
D000818:Animals; D001755:Blastocyst / Q000378:metabolism / Q000473:pathology; D001779:Blood Coagulation Factors / Q000378:metabolism; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D010064:Embryo Implantation; D005260:Female; D006487:Hemostasis; D006801:Humans; D008431:Maternal-Fetal Exchange; D008597:Menstrual Cycle; D009389:Neovascularization, Pathologic; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism* / Q000473:pathology; D011374:Progesterone / Q000378:metabolism
D001779:Blood Coagulation Factors; D011374:Progesterone