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Hum. Reprod. Advance Access published online on July 8, 2004

Human Reproduction, doi:10.1093/humrep/deh411
© 2004 by European Society of Human Reproduction and Embryology
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Received November 5, 2003
Revised May 18, 2004
Accepted June 16, 2004

Article

Soluble factors from human endometrium promote angiogenesis and regulate the endothelial cell transcriptome

Cristin Print 1* *, Reija Valtola 1 *, Amanda Evans 1, Khashayar Lessan 1, Shazia Malik 2, Stephen Smith 2

1 Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK
2 Department of Obstetrics and Gynaecology, The Rosie Hospital, Robinson Way, Cambridge CB2 2SW, UK

* To whom correspondence should be addressed. E-mail: cgp22{at}cam.ac.uk.


   Abstract

BACKGROUND: Angiogenesis and vascular remodeling play critical roles in the cyclical growth and regression of endometrium. They also appear to play roles in the pathogenesis of endometriosis. METHODS and RESULTS: Supernatants were collected from cultured endometrium isolated from women with and without endometriosis. These supernatants induced endothelial cell proliferation and angiogenesis in vitro. They contained vascular endothelial growth factor (VEGF)-A, and their proliferative effects on endothelial cells were partially abrogated by a blocking anti-VEGF-A antibody. Gene array analysis showed that culture supernatants from proliferative phase endometrium, and to a lesser extent secretory phase endometrium, induced significant changes in the transcriptome of endothelial cells. We could not detect any association between endometriosis and the ability of endometrial-derived soluble factors to promote angiogenesis or to regulate the endothelial transcriptome. In addition, we could not detect any association between endometriosis and the concentration of VEGF-A in supernatants from cultured endometrium or in menstrual effluent. CONCLUSIONS: We have shown that endometrium cultured in vitro produced soluble factors, including VEGF-A, that promoted angiogenesis. Proliferative phase endometrium promoted significant endothelial cell transcriptome changes that appear overall to be pro-angiogenic. These transcriptome changes provide insight into the dynamic control of vessel structure on which both eutopic endometrium and endometriotic lesions depend.

Keywords: endometrious; gene array; VEGF-A; transcriptome.

*These authors contributed equally to this work


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