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Progestin and Thrombin Regulate Tissue Factor Expression in Human Term Decidual Cells

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Frederick Schatz, Ph.D., Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, Room 810 LCI, P.O. Box 208063 New Haven, Connecticut 06520. E-mail: frederick.schatz{at}yale.edu.

Context: Perivascular cell membrane-bound tissue factor (TF) initiates hemostasis via thrombin generation. The identity and potential regulation of TF-expressing cells at the human maternal-fetal interface that confers hemostatic protection during normal and preterm delivery is unclear.

Objectives: The objective of the study were to identify TF-expressing cells at the maternal-fetal interface in term and preterm decidual sections by immunohistochemistry and evaluate progestin, thrombin, TNF-, and IL-1β effects on TF expression by cultured human term decidual cells (DCs).

Interventions and Main Outcome Measures: Serial placental sections were immunostained for TF. Leukocyte-free term DC monolayers were incubated with 10^–8 M estradiol (E2) or E2 plus 10^–7 M medroxyprogestrone acetate (MPA) ± thrombin or TNF- or IL-1β. ELISA and Western blotting assessed TF in cell lysates. Quantitative real-time RT-PCR measured TF mRNA levels.

Results: Immunolocalized TF in DC membranes in preterm and term placental sections displayed higher Histologic Scores than villous mesenchymal cells (P < 0.05). TF was undetected in interstitial or extravillous trophoblasts. Compared with DCs incubated with E2, MPA and 2.5 U/ml thrombin each doubled TF levels (P < 0.05) and E2 + MPA + thrombin further doubled TF levels (P < 0.05), whereas TNF- and IL-1β were ineffective. Western blotting confirmed the ELISA results. Quantitative RT-PCR revealed corresponding changes in TF mRNA levels.

Conclusions: In human term placental sections, DC-expressed TF exceeds that of other cell types at the maternal-fetal interface and is localized at the cell membranes in which it can bind to factor VII and meet the hemostatic demands of labor and delivery via thrombin formation. Unlike the general concept that TF is constitutive in cells that highly express it, MPA and thrombin significantly enhanced TF expression in term DC monolayers.