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

Seifeldin Sadek, Terry A. Jacot, Diane M. Duffy, David F. Archer
F&S science · 2024 · vol. 5(4) , pp. 379–385 · doi:10.1016/j.xfss.2024.07.007 · PMID:39038609 · W4400844096
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Prostaglandin E2 increases PAI-1 in normal but not heavy menstrual bleeding endometrial endothelial cells, suggesting a role in regulating fibrinolysis during normal cycles.

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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.

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MeSH descriptors

Dinoprostone Dinoprostone Dinoprostone Endometrium Endometrium Endometrium Endothelial Cells Endothelial Cells Endothelial Cells Endothelial Cells Menorrhagia Menorrhagia Plasminogen Activator Inhibitor 1 Plasminogen Activator Inhibitor 1 Tissue Plasminogen Activator Tissue Plasminogen Activator Adult Cells, Cultured Female Humans

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