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.