Prostaglandin E 2 regulates the plasminogen activator pathway in human endometrial endothelial cells: a new in vitro model to investigate heavy menstrual bleeding.

Autor: Sadek S; The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia. Electronic address: ses2020@qatar-med.cornell.edu., Jacot TA; Department of Obstetrics and Gynecology, Jones Institute for Reproductive Medicine/Eastern Virginia Medical School, Norfolk, Virginia., Duffy DM; Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia., Archer DF; The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, Virginia.
Jazyk: angličtina
Zdroj: F&S science [F S Sci] 2024 Jul 20. Date of Electronic Publication: 2024 Jul 20.
DOI: 10.1016/j.xfss.2024.07.007
Abstrakt: Objective: To study the role of PGE 2 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 E 2 and PGE 2 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 PGE 2 and receptor-selective agonists.
Results: Prostaglandin E 2 increased total PAI-1 levels in NMB-HEECs, but not in HMB-HEECs, which had higher baseline PAI-1 levels. PGE 2 receptors (PTGER)1 and PTGER2 agonists increased PAI-1 in NMB-HEECs, whereas PTGER3 and PTGER4 did not. Prostaglandin E 2 had no effect on tPA levels in either NMB-HEECs or HMB-HEECs.
Conclusions: Prostaglandin E 2 , 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 2 effect and elevated baseline PAI-1 in HMB-HEECs support using this in vitro model to further understand prostaglandin pathways in NMB and HMB.
Competing Interests: Declaration of Interests S.S. and T.A.J. report funding from Jones Family Foundation, Eastern Virginia Medical School and Commonwealth Health Research Board for the submitted work. D.M.D. reports funding from Jones Family Foundation, Eastern Virginia Medical School and Commonwealth Health Research Board for the submitted work; funding from NIH, Organon & Co. (product donation – no direct financial support), Wisconsin National Primate Research Center, and American Heart Association; consulting fees from InnovaGyn Inc; InnovaGyn Inc, Chief Science Officer member of the Board of Directors; Society for the Study of Reproduction, Chair, Development Committee unpaid; Federation of American Societies for Experimental Biology (FASEB) Chair, Meetings Committee unpaid; and stock options from InnovaGyn Inc. outside the submitted work. D.F.A. reports funding from Jones Family Foundation, Eastern Virginia Medical School and Commonwealth Health Research Board for the submitted work; grant support for research from Jones Family Foundation at Eastern Virginia Medical School; and stock options as CEO of InnovaGyn, Inc outside the submitted work.
(Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE