Prostaglandin E2 regulates the plasminogen activator pathway in human endometrial endothelial cells: a new in vitro model to investigate heavy menstrual bleeding

Abstract

Objective

To study the role of PGE₂ in regulating plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in human primary endometrial endothelial cells (HEECs) from women with normal menstrual bleeding (NMB) and heavy menstrual bleeding (HMB).

Design

In vitro study using endometrial endothelial cells.

Setting

Research laboratory setting.

Patients

Women with NMB and HMB provided endometrial biopsy samples.

Interventions

Prostaglandin E₂ and PGE₂ receptor-selective agonists were administered to cultured HEECs.

Main Outcome Measures

Levels of PAI-1 and tPA in NMB-HEECs and HMB-HEECs after treatment with PGE₂ and receptor-selective agonists.

Results

Prostaglandin E₂ increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PGE₂ receptors (PTGER)1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, whereas PTGER3 and PTGER4 did not. Prostaglandin E₂ had no effect on tPA levels in either NMB-HEECs or HMB-HEECs.

Conclusions

Prostaglandin E₂, through PTGER1 and PTGER2, regulates the plasminogen activator system in NMB-HEECs, suggesting a role in reducing fibrinolytic activity during normal menstrual cycles. The lack of PGE₂ effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in NMB and HMB.