Mol. Hum. Reprod. Advance Access originally published online on January 16, 2006
Molecular Human Reproduction 2006 12(1):11-18; doi:10.1093/molehr/gah257
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Membrane-type matrix metalloproteinases and vascularization in human endometrium during the menstrual cycle
1Division of Biomedical Research, TNO Quality of Life, 2Department of Gynaecology and Reproductive Medicine, Leiden University Medical Centre, Leiden, 3Department of Obstetrics and Gynaecology, Bronovo Hospital, The Hague, 4Department of Obstetrics and Gynaecology, St. Fransiscus Gasthuis, Rotterdam, 5Department of Pathology, VU University Medical Centre and 6Department of Physiology, Institute for Cardiovascular Research, VU University Medical Centre, Amsterdam, The Netherlands
7 To whom correspondence should be addressed at: VU University Medical Centre, Department of Physiology, Institute for Cardiovascular Research, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands. E-mail: v.vanhinsbergh{at}vumc.nl
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 endometrial 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.
Key words: angiogenesis/endometrium/endothelium/MT3-MMP/MT-MMP
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