27 - 30 May 2005

THE SYNDECAN-FAMILY: ADHESION PROTEINS IN THE HUMAN ENDOMETRIUM A. Germeyer, M. Klinkert, M. Prasadajudo, A. Huppertz, T. Strowitzki, M. von Wolff Department of Gynaecological Endocrinology University Hospital Heidelberg Germany

Introduction: For the blastocyst implantation a coordinated interaction between blastocyst and endometrium is crucial. This interaction depends on a regulated gene and protein expression, including many adhesion molecules. The Syndecan family containing four heparansulfate glycosaminoglycan proteins, are known to influence adhesion, cell-cell-interaction, migration and proliferation in many organs. In the endometrium, where all these processes take place each cycle, little is known about the expression of this family of adhesion proteins. In this study we examine the localization and regulation the individual Syndecan members within the human endometrium. This may help to better understand the underlying mechanisms of implantation.

Material and Methods: Endometrial biopsies of healthy female of reproductive age with regular menses were taken after informed consent from Heidelberger Protocol. RNA expression of 20 and protein expression of 8 biopsies were analysed. Realtime PCR or RNA Protection Assay of whole tissue and tissue fractions after magnetic bead isolation were performed. Genes were normalized to GAPDH and statistical analysis with ANOVA and Wilcoxon Rank Sum Test were performed. Protein expression via immunocytochemistry for syndecan-1 and -4, as well as western blots for syndecan-1 were performed using commercially available antibodies.

Results: In whole tissue RNA of all four Syndecan members were found throughout the menstrual cycle. While Syndecan-2 RNA was expressed at the highest level only syndecan-1 and Syndecan-4 showed statistical significant regulation. Cell fractions of separated epithelial cells and stromal cells, free of immune as well as endothelial cells, showed expression of all Syndecan members. While Syndecan-1 and Syndecan-4 were found predominantly in epithelial cells, this trend could not be seen in Syndecan-2 and Syndecan-3. An up-regulation of syndecan-1, as well as Syndecan-4 in epithelial cells could be noted during the secretory phase. On protein level syndecan-1 and -4 seemed only to be expressed in high levels in epithelial cells.

Conclusions: RNA expression of all four Syndecan members were noted for the first time throughout the menstrual cycle with an up-regulation of Syndecan-1 and –4 during the secretory phase. Syndecans, proteins known to promote adhesion, migration and cell proliferation in several organs, could potentially influence the cyclic proliferation of the endometrium via VEGF (vascular endothelial growth factor), an important angiogenetic factor. In addition they may influence throphoblast adhesion and invasion. Nevertheless further studies investigating the function of the individual syndecan members in the endometrium needs to be performed.

List of abstracts from the 3rd International Conference on the Female Reproductive Tract