Julia Spratte1, Frauke Bornkessel2, Florian Schütz3, Marek Zygmunt2, Herbert Fluhr3. 1. Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany. julia.spratte@med.uni-heidelberg.de. 2. Department of Obstetrics and Gynecology, University of Greifswald, Sauerbruchstr, 17475, Greifswald, Germany. 3. Department of Obstetrics and Gynecology, University of Heidelberg, Im Neuenheimer Feld 440, 69120, Heidelberg, Germany.
Abstract
PURPOSE: The aim of this paper is to study the impact of heparin on the response of human endometrial stromal cells (ESCs) to interleukin (IL)-1β during decidualization in vitro. METHODS: ESCs were isolated from hysterectomy specimens of premenopausal women undergoing hysterectomy for benign reasons; decidualized in vitro and incubated in parallel with unfractionated heparin or tinzaparin; and stimulated with IL-1β at days 0, 3, 6, and 9 during decidualization. IL-6, IL-11, and leukemia inhibitory factor (LIF) were analyzed using ELISAs and real-time RT-PCR. Cell viability was determined by a fluorometric assay. RESULTS: IL-1β dose-dependently stimulated IL-6, IL-11, and LIF in distinct patterns in ESCs during decidualization. Unfractionated heparin as well as tinzaparin attenuated the IL-1β-mediated induction of IL-6, IL-11, and LIF on protein and messenger RNA (mRNA) levels. The relative effects of heparin and tinzaparin were getting more pronounced during the time course of decidualization. CONCLUSIONS: Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1β-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation.
PURPOSE: The aim of this paper is to study the impact of heparin on the response of human endometrial stromal cells (ESCs) to interleukin (IL)-1β during decidualization in vitro. METHODS: ESCs were isolated from hysterectomy specimens of premenopausal women undergoing hysterectomy for benign reasons; decidualized in vitro and incubated in parallel with unfractionated heparin or tinzaparin; and stimulated with IL-1β at days 0, 3, 6, and 9 during decidualization. IL-6, IL-11, and leukemia inhibitory factor (LIF) were analyzed using ELISAs and real-time RT-PCR. Cell viability was determined by a fluorometric assay. RESULTS: IL-1β dose-dependently stimulated IL-6, IL-11, and LIF in distinct patterns in ESCs during decidualization. Unfractionated heparin as well as tinzaparin attenuated the IL-1β-mediated induction of IL-6, IL-11, and LIF on protein and messenger RNA (mRNA) levels. The relative effects of heparin and tinzaparin were getting more pronounced during the time course of decidualization. CONCLUSIONS: Unfractionated heparin and the low molecular weight heparin tinzaparin have modulating effects on IL-1β-induced endometrial cytokines of the IL-6 family during decidualization. These effects of heparins beyond their classical anti-coagulatory properties might have implications on the regulation of endometrial receptivity and early implantation.
Authors: Herbert Fluhr; Julia Spratte; Jens Ehrhardt; Frauke Steinmüller; Peter Licht; Marek Zygmunt Journal: Fertil Steril Date: 2009-12-03 Impact factor: 7.329