Membrane-type matrix metalloproteinases and vascularization in human endometrium during the menstrual cycle.
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.
Plaisier
Margreet
M
Division of Biomedical Research, TNO Quality of Life, Department of Gynaecology and Reproductive Medicine, Leiden University Medical Centre, The Netherlands.
Koolwijk
Pieter
P
Hanemaaijer
Roeland
R
Verwey
Robert A
RA
van der Weiden
Robin M F
RM
Risse
Elle K J
EK
Jungerius
Clarissa
C
Helmerhorst
Frans M
FM
van Hinsbergh
Victor W M
VW
D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D004717:Endometrium / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology*; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D006801:Humans; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000502:physiology*; D008597:Menstrual Cycle / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000502:physiology*
D053504:Matrix Metalloproteinases, Membrane-Associated