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Mol. Hum. Reprod. Advance Access originally published online on July 8, 2004
Molecular Human Reproduction 2004 10(9):655-663; doi:10.1093/molehr/gah081
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Molecular Human Reproduction vol. 10 no. 9 © European Society of Human Reproduction and Embryology 2004; all rights reserved

Differential localization and expression of urokinase plasminogen activator (uPA), its receptor (uPAR), and its inhibitor (PAI-1) mRNA and protein in endometrial tissue during the menstrual cycle

J. Nordengren1, R. Pilka1,3, V. Noskova1, A. Ehinger2, H. Domanski2, C. Andersson2, G. Høyer-Hansen4, S.R. Hansson1 and B. Casslén1,5

Departments of 1Gynaecology & Obstetrics and 2Pathology, University Hospital, Lund, Sweden, 3Department of Gynaecology & Obstetrics, Palacky University, Olomouc, Czech Republic and 4Finsen Laboratory, Copenhagen, Denmark

5 To whom correspondence should be addressed. Email: bertil.casslen{at}gyn.lu.se

Normal endometrium is a highly dynamic tissue, which responds to ovarian steroids with cyclic proliferation, differentiation (secretion), and degradation (menstruation). The urokinase plasminogen activator (uPA)-dependent proteolytic cascade as well as ligand activation of the uPA receptor (uPAR) is critically involved in physiological as well as pathophysiological aspects of tissue expansion and remodelling. Cyclic variation and distribution of uPA, uPAR and plasminogen activator inhibitor 1 (PAI-1) mRNA were examined by in situ hybridization, real-time PCR and northern blot in normal endometrium. Their corresponding proteins were localized with immunohistochemistry. uPA mRNA is exclusively expressed by stromal cells, whereas uPA protein is present in both epithelial and stromal cells. Immunostaining for uPA protein is reduced or undetectable at midcycle, thus coinciding with peak concentration of uPA in the uterine fluid. uPAR mRNA is expressed by epithelial cells in the proliferative phase and by stromal cells in the secretory phase. However, epithelial cells stain for uPAR protein throughout the cycle, suggesting that uPAR may detach from stromal cells and then bind to epithelial cells in the secretory phase. PAI-1 mRNA is located in vessel walls. The late secretory phase has greatly increased expression of all three mRNA and their proteins, mainly in pre-decidual cells in the superficial stroma. Discordant localization of the mRNA and proteins suggest that uPA is produced by stromal cells, released and bound to epithelial cells in both the proliferative and secretory phases, whereas uPAR is released from the stroma and bound to epithelial cells in the secretory phase. Also, the present data together with earlier reports suggest that uPA is released from the epithelial cells to the uterine fluid.

Key words: endometrium/epithelial cells/menstrual cycle/uPA/uPAR


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R. Pilka, V. Noskova, H. Domanski, C. Andersson, S. Hansson, and B. Casslen
Endometrial TIMP-4 mRNA is expressed in the stroma, while TIMP-4 protein accumulates in the epithelium and is released to the uterine fluid
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