Decidual cell-expressed tissue factor maintains hemostasis in human endometrium

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Hemostasis

Background:

• Decidualized stromal cells in the human endometrium express tissue factor (TF), the primary initiator of hemostasis.
• This suggests a mechanism for preventing hemorrhage during endovascular trophoblast invasion.
• Ovarian steroids, particularly progestins, play a key role in regulating endometrial function during pregnancy.

Purpose of the Study:

• To investigate the role of tissue factor (TF) in decidualized endometrial cells.
• To elucidate the mechanisms by which ovarian steroids regulate TF expression.
• To identify the key transcription factors involved in TF regulation during decidualization.

Main Methods:

• Primary human endometrial stromal cells (HESCs) were cultured and treated with progestins and estradiol (E2).
• TF mRNA and protein levels were quantified using RT-PCR and Western blotting.
• TF promoter activity was assessed using transient transfection assays with reporter constructs.
• The role of transcription factors Sp1 and EGR-1 was investigated using site-directed mutagenesis and overexpression studies.
• Epidermal growth factor receptor (EGFR) involvement was explored using EGFR agonists.

Main Results:

• Progestins significantly enhanced TF mRNA and protein levels in HESCs, an effect further amplified by E2.
• TF upregulation was mediated by the progesterone receptor and maintained long-term.
• EGFR activation, in conjunction with progestin, was required for maximal TF induction.
• TF expression is transcriptionally regulated, with Sp1 sites on the TF promoter being dominant.
• The ratio of Sp1 to Sp3 transcription factors increased during decidualization.

Conclusions:

• Decidualized endometrial stromal cells express TF, contributing to hemostasis and potentially preventing uterine hemorrhage.
• Progestin-induced TF expression is a key decidualization marker, regulated transcriptionally.
• The EGFR pathway, alongside progesterone receptor signaling and Sp1 transcription factor activity, mediates progestin-enhanced TF expression.