Mol. Hum. Reprod. Advance Access published online on June 29, 2006
Molecular Human Reproduction, doi:10.1093/molehr/gal055
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1 Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden; Department of Obstetrics and Gynecology, Palacky University, Olomouc, Czech Republic, Lund, Sweden
* To whom correspondence should be addressed. We have previously reported that endometrial mRNA expression of both tissue inhibitors of metalloproteinase-4 (TIMP-4) and matrix metalloproteinase-26 (MMP-26) peaks in the early secretory phase, which implies a role in implantation. The objective of this study was to compare the distribution of TIMP-4 and MMP-26 in endometrial tissue and uterine fluid over the menstrual cycle. Endometrial tissue was analysed with in situ hybridization and immunohistochemistry to localize mRNA and protein for TIMP-4 and MMP-26 in the same set of samples. TIMP-4 mRNA was quantified in separated stromal and epithelial cells using real-time PCR. Uterine fluid was analysed with western blotting. TIMP-4 mRNA was exclusively localized to the stroma, whereas MMP-26 mRNA was expressed by epithelial cells. TIMP-4 protein was only occasionally found in the stroma but was consistently present in granules of the apical part of luminal and glandular epithelial cells. TIMP-4, but not MMP-26, was demonstrated in uterine fluid. Thus, TIMP-4 is produced in the stroma only, secreted by stromal cells, taken up by epithelial cells, accumulated in apical granules and finally secreted to the uterine fluid. Maximal expression of MMP-26, and its strongest inhibitor TIMP-4, in the early and mid-secretory phase suggests a role during implantation. MMP-26 is stored in epithelial cells in its active form, is not released spontaneously and is controlled by TIMP-4 in both stroma and uterine fluid.
Received January 31, 2006
Revised May 16, 2006
Accepted May 23, 2006
Article
Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid
R. Pilka 1,
V. Noskova 2,
H. Domanski 3,
C. Andersson 3,
S. Hansson 2,
and
B. Casslén 2 *
2 Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden
3 Department of Pathology, University Hospital, Lund, Sweden
B. Casslén, E-mail: bertil.casslen{at}med.lu.se
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