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Mol. Hum. Reprod. Advance Access originally published online on January 5, 2008
Molecular Human Reproduction 2008 14(1):41-51; doi:10.1093/molehr/gam085
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Pericellular-acting proteases in human first trimester decidua

Margreet Plaisier1,2, Pieter Koolwijk2,3, Florian Willems4, Frans M. Helmerhorst1,5 and Victor W.M. van Hinsbergh3

1Division of Reproductive Medicine, Department of Gynaecology, Leiden University Medical Centre, PO Box 9600, 2300 RC, Leiden, The Netherlands 2Gaubius Laboratory TNO-QoL, Department Biomedical Research, Zernikedreef 9, 2333 CK, Leiden, The Netherlands 3Department of Physiology, Institute for Cardiovascular Research, VU Medical Centre, van der Boeckhorststraat 7, 1081 BT, Amsterdam, The Netherlands 4STIMEZO Plus Clinic, van Beverninckstraat 134, 2582 VL, The Haque, The Netherlands

5 Correspondence address. Fax: +31-71-5248181; E-mail: M.Plaisier{at}lumc.nl, F.M.Helmerhorst{at}lumc.nl

Proteolysis is essential for decidual development during embryonic implantation, but little is known regarding the expression and functions of membrane-type matrix metalloproteinases (MT-MMPs) and urokinase-type plasminogen activator (uPA) and its receptor uPAR in decidua. Therefore, their protein and mRNA levels were analysed in three first trimester decidual tissues, decidual secretory endometrium (DSE), decidua parietalis (DP) and basalis (DB). Decidua was obtained during first trimester pregnancy termination. uPA, uPAR, and MT1/2/3/5-MMP expression were studied by RT-PCR and immunohistochemistry, and CD56-positive uNK cells and CD68-positive macrophages were quantified in serial sections. The mRNAs and antigens of all proteases and uPAR were detectable in the decidual tissues and extravillous trophoblasts (EVT). mRNA levels of all proteases and uPAR, except MT5-MMP, were elevated in both DB and DP compared to DSE, being significant for MT1-MMP and uPAR in DP. MT2- and MT3-MMP mRNAs in DB were 24- and 10-fold higher than in DSE, and 19- and 7-fold increased compared to DP. At the protein level uPA and uPAR were particularly elevated in DB, while pro-angiogenic MT1- and MT3-MMPs were elevated in both DB and DP compared to DSE. MT2-MMP was prominently present in all conditions. The number of uNK cells was increased in DB and DP versus DSE, while a comparable increase in macrophages did not reach statistical significance. These data are consistent with a differential regulation of pericellular proteases in decidua by pregnancy-induced hormones, immune cells and EVT.

Key words: decidua/first trimester/matrix metalloproteinases/trophoblast/uNK cells

Submitted on August 24, 2007; resubmitted on November 4, 2007; accepted on November 30, 2007.


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