Mol. Hum. Reprod. Advance Access published online on January 16, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gah257
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1 Division of Biomedical Research, TNO Quality of Life; Department of Gynaecology and Reproductive Medicine, Leiden University Medical Centre, Leiden
* To whom correspondence should be addressed. Endometrial angiogenesis is essential for a vascularized receptive endometrium. Previously, we described that membrane type-3 metalloproteinase (MT3-MMP) is associated with endometrial angiogenesis in vitro. The association of MT-MMPs with endome-trial angiogenesis in vivo is unknown. Therefore, this study analysed the presence of MT-MMPs in human endometrium and their correlation with neovascularization. RNA/protein expressions of the six MT-MMPs were determined in cultured endometrial cells. Vascularization parameters and MT-MMP expressions in vivo were evaluated by immunohistochemistry in serial endometrium sections. MT1-, MT2-, MT3- and MT4-MMP antigens were expressed in cultured endometrial endothelial cells. MT2-, MT3- and MT4-MMP were expressed by endothelium during the proliferative and secretory phase. Strikingly, these phases showed elevated vascularization, elevated total vascular surface in proliferative phases, elevated number of vessels in proliferative/late secretory phases and increased luminal surface in the proliferative phases. All MT-MMP antigens were expressed in various endometrial cell types in vivo, with decreased levels during the early secretory phase. In conclusion, all MT-MMPs are expressed in endometrium in a cycle-dependent pattern. The vascular expression of MT2-, MT3- and MT4-MMP correlated with angiogenic episodes of the cycle. Since MT2- and MT3-MMP are known to regulate tube formation, these findings support earlier in vitro data on the role of MT3-MMP in endometrial angiogenesis. Additionally, MT2-MMP appears to be associated with endometrial neovascularization also.
Received August 16, 2005
Accepted December 4, 2005
Article
Membrane-type matrix metalloproteinases and vascularization in human endometrium during the menstrual cycle
Margreet Plaisier 1,
Pieter Koolwijk 2,
Roeland Hanemaaijer 2,
Robert A.Verwey 3,
Robin M.F. van der Weiden 4,
Elle K.J.Risse 5,
Clarissa Jungerius 6,
Frans M.Helmerhorst 7,
and
Victor W.M. van Hinsbergh 6 *
2 Division of Biomedical Research, TNO Quality of Life
3 Department of Obstetrics and Gynaecology, Bronovo Hospital, The Hague
4 Department of Obstetrics and Gynaecology, St. Fransiscus Gasthuis, Rotterdam
5 Department of Pathology, VU University Medical Centre, Amsterdam, The Netherlands
6 Department of Physiology, Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands
7 Department of Gynaecology and Reproductive Medicine, Leiden University Medical Centre, Leiden
Victor W.M. van Hinsbergh, E-mail: v.vanhinsbergh{at}vumc.nl
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