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

F S Sci. 2024 Nov;5(4):379-385. doi: 10.1016/j.xfss.2024.07.007. Epub 2024 Jul 20.

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.

Keywords: Endometrium; endothelial cell; menstrual bleeding; plasminogen activator system; prostaglandin E(2).

MeSH terms

  • Adult
  • Cells, Cultured
  • Dinoprostone* / metabolism
  • Dinoprostone* / pharmacology
  • Endometrium* / metabolism
  • Endometrium* / pathology
  • Endothelial Cells* / drug effects
  • Endothelial Cells* / metabolism
  • Endothelial Cells* / pathology
  • Female
  • Humans
  • Menorrhagia* / metabolism
  • Plasminogen Activator Inhibitor 1* / metabolism
  • Receptors, Prostaglandin E / agonists
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP1 Subtype / agonists
  • Receptors, Prostaglandin E, EP1 Subtype / genetics
  • Receptors, Prostaglandin E, EP1 Subtype / metabolism
  • Tissue Plasminogen Activator* / metabolism

Substances

  • Dinoprostone
  • Plasminogen Activator Inhibitor 1
  • Tissue Plasminogen Activator
  • SERPINE1 protein, human
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP1 Subtype