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Hum. Reprod. Advance Access originally published online on July 8, 2004
Human Reproduction 2004 19(10):2356-2366; doi:10.1093/humrep/deh411
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Human Reproduction vol. 19 no. 10 © European Society of Human Reproduction and Embryology 2004; all rights reserved

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

Cristin Print1,3,*, Reija Valtola1,*, Amanda Evans1, Khashayar Lessan1, Shazia Malik2 and Stephen Smith2

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

3 To whom correspondence should be addressed at: Department of Pathology, Cambridge University, Tennis Court Road, Cambridge, CB2 1QP, UK. Email: cgp22{at}cam.ac.uk

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.

Key words: endometrious/gene array/VEGF-A/transcriptome

* These authors contributed equally to this work


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