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
{"title":"Prostaglandin E<sub>2</sub> regulates the plasminogen activator pathway in human endometrial endothelial cells: a new in vitro model to investigate heavy menstrual bleeding.","authors":"Seifeldin Sadek, Terry A Jacot, Diane M Duffy, David F Archer","doi":"10.1016/j.xfss.2024.07.007","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>To study the role of PGE<sub>2</sub> 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).</p><p><strong>Design: </strong>In vitro study using endometrial endothelial cells.</p><p><strong>Setting: </strong>Research laboratory setting.</p><p><strong>Patients: </strong>Women with NMB and HMB provided endometrial biopsy samples.</p><p><strong>Interventions: </strong>Prostaglandin E<sub>2</sub> and PGE<sub>2</sub> receptor-selective agonists were administered to cultured HEECs.</p><p><strong>Main outcome measures: </strong>Levels of PAI-1 and tPA in NMB-HEECs and HMB-HEECs after treatment with PGE<sub>2</sub> and receptor-selective agonists.</p><p><strong>Results: </strong>Prostaglandin E<sub>2</sub> increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PGE<sub>2</sub> receptors (PTGER)1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, whereas PTGER3 and PTGER4 did not. Prostaglandin E<sub>2</sub> had no effect on tPA levels in either NMB-HEECs or HMB-HEECs.</p><p><strong>Conclusions: </strong>Prostaglandin E<sub>2</sub>, 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 PGE<sub>2</sub> effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in NMB and HMB.</p>","PeriodicalId":73012,"journal":{"name":"F&S science","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"F&S science","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xfss.2024.07.007","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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.