Human embryo–conditioned medium stimulates in vitro endometrial angiogenesis

Kapiteijn, Kitty; Koolwijk, Pieter; van der Weiden, Robin M.F.; van Nieuw Amerongen, Geerten; Plaisier, Margreet; van Hinsbergh, Victor W.M.; Helmerhorst, Frans M.

doi:10.1016/j.fertnstert.2005.11.029

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Volume 85, Supplement 1 , Pages 1232-1239, April 2006

Human embryo–conditioned medium stimulates in vitro endometrial angiogenesis

Kitty Kapiteijn, M.D.
- Division of Biomedical Research, TNO Quality of Life, Leiden, The Netherlands
- Department of Gynecology, and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands
Pieter Koolwijk, Ph.D.
- Division of Biomedical Research, TNO Quality of Life, Leiden, The Netherlands
- Reprint requests: Pieter Koolwijk, Ph.D., TNO Quality of Life, Zernikedreef 9, 2333 CK Leiden, The Netherlands (FAX: +31 71 5181901)
Robin M.F. van der Weiden, M.D.
- Department of Obstetrics and Gynecology, St. Franciscus Gasthuis, Rotterdam
Geerten van Nieuw Amerongen, Ph.D.
- Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
Margreet Plaisier, M.D.
- Division of Biomedical Research, TNO Quality of Life, Leiden, The Netherlands
- Department of Gynecology, and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands
Victor W.M. van Hinsbergh, Ph.D.
- Division of Biomedical Research, TNO Quality of Life, Leiden, The Netherlands
- Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands
Frans M. Helmerhorst, M.D.
- Department of Gynecology, and Reproductive Medicine, Leiden University Medical Center, Leiden, The Netherlands

Received 5 August 2005; received in revised form 3 November 2005; accepted 3 November 2005.

Objective

Successful implantation and placentation depend on the interaction between the endometrium and the embryo. Angiogenesis is crucial at this time. In this article we investigate the direct influence of the human embryo on in vitro endometrial angiogenesis.

Design

In vitro study.

Setting

Human endometrial microvascular endothelial cells (hEMVEC) grown on an in vitro angiogenesis model.

Intervention(s)

Conditioned media (CM) of human embryos were used to stimulate in vitro angiogenesis.

Main Outcome Measure(s)

In vitro angiogenesis of hEMVEC.

Result(s)

Conditioned media of human embryos, containing significant amounts of vascular endothelial growth factor (VEGF)–A, as determined by enzyme-linked immunosorbent assay (ELISA), caused an increase in hEMVEC tube formation. This effect was prevented by soluble VEGF receptor 1, which quenches VEGF-A activity. Recombinant EGF alone and leukemia inhibitory factor in combination with VEGF-A stimulated hEMVEC tube formation. None of the other tested recombinant mediators, which have been described as produced by the early embryo/trophoblast (interleukin (IL) 10, transforming growth factor (TGF) β, placental growth factor, hCG, colony-stimulating factor 1, interferon-γ, insulin-like growth factor I and II, IL-6, platelet-derived growth factor, and TGFα), had an effect on tube formation by hEMVEC.

Conclusion(s)

For the first time, it is shown that the human embryo is able to stimulate in vitro endometrial angiogenesis at the time of implantation, a process that is mediated by VEGF-A.

Key Word: Endometrial angiogenesis