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Prof. Dr. med. Dr. rer. nat.
Hans-Werner Denker
email:
Hans-Werner Denker – University Duisburg-Essen Deutsche Version English Version

Embryo Implantation III: Endometrial Receptivity

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Overview

Main Findings:

  • Embryo implantation in the uterus is a fascinating biological phenomenon: On one hand it is decisive for the establishment of pregnancy, on the other it may serve as a model for the interaction of invasive cells (trophoblast in this case) with their host tissue (in this case the endometrium).
  • Implantation can start only if trophoblast and its partner tissue, the endometrium of the uterus, have simultaneously entered a special cell biological state: invasiveness in case of the trophoblast, receptivity in case of the endometrium.
  • Serine proteinases while playing a central role in the dissolution of blastocyst coats (see topic 4) do not appear to be involved in penetration of the trophoblast through the uterine epithelium, as shown by our proteinase inhibition experiments in vivo. Therefore, explanations for this latter process must consider details of the cell biology of the two partner tissues.
  • The cell biology of trophoblast invasiveness and of endometrial receptivity had previously remained largely unexplained. In order to make progress here it was helpful to first realize that we are dealing with a phenomenon which can be called a cell biological paradox: Trophoblast and uterine epithelium make their first adhesive contact with their apical cell poles although in other simple epithelia these parts of cells use to be non-adhesive (and even anti-adhesive). In a theoretical model we have postulated that there must be parallels to another biological phenomenon, i.e. the so-called embryonic fusion processes. In that case (and in tumor cell invasion as well) epithelial-mesenchymal transition (EMT) has been found to play a crucial role. We thus have proposed that it will be of heuristic value to make use of the advances of EMT research for studies on embryo implantation (and vice versa).
  • A detailed experimental analysis based on this concept revealed that changes in apico-basal polarity of the two partner epithelia (trophoblast and uterine epithelium) must be a key issue here, at acquisition of invasiveness and receptivity, respectively. However, the uterine epithelium does not show complete EMT but strategically uses elements of EMT processes: partial loss or destabilisation of polarity.
  • We have developed in vitro systems which allow studying these phenomena using human cell lines and which avoid involving human embryos: adhesion and invasion models using multicellular spheroids of trophoblast cells, and endometrial cell lines or fragments of endometrial tissue. We consider it ethically unacceptable to use human embryos.
  • For the first time the development of adhesive force was measured between living cells during attachment; signalling mechanisms and role of cytoskeleton; pharmacologic manipulation of cell attachment; role of various adhesion proteins, glycoconjugates and lectins.
  • This approach has allowed gaining insight into basic aspects of endometrial receptivity, specifically the cell biology of the uterine epithelium during trophoblast adhesion and invasion. The data have led to a change of traditional views about the role of the host tissue in embryo implantation: The uterine epithelium appears not to be passive but to participate actively in trophoblast adhesion and penetration and may thus control it in a subtle way from the start.

List of Publications

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SHENG, G., THOMPSON, E., NEWGREEN, D., DENKER, H.-W.:
Twenty Years on for The Epithelial-Mesenchymal Transition International Association (TEMTIA): An Interview with Co-Founders Erik Thompson and Donald Newgreen.
Cells Tissues Organs 211(2): 252-260 (2022). DOI: 10.1159/000518250
PubMed   CTO Website (free access)

DENKER, H.-W.:
Rise of the rabbit model for implantation research. A commemoration of the scientific work of Bent G. Boving (1920-2019).
Biology of Reproduction 102 (6): 1170-1176 (2020). DOI: 10.1093/biolre/ioaa038
PubMed   BOR   BOR (free access)

DENKER, H.-W.:
Implantation: Cell biology of embryo penetration route revisited.
(Comment on: UCHIDA, H. et al.: How to create an embryo penetration route. Am. J. Reprod. Immunol. 75(3): 326-332, 2016. DOI: 10.1111/aji.12476)
Am. J. Reprod. Immunol. 76(6): 429-431 (2016). DOI: 10.1111/aji.12591
PubMed   AJRI   pdf-download (219 KB)   summary (68 KB)

HENEWEER, C., SCHMIDT, M., DENKER, H.-W., THIE, M.:
Molecular mechanisms in uterine epithelium during trophoblast binding:
the role of small GTPase RhoA in human uterine Ishikawa cells.

Journal of Experimental & Clinical Assisted Reproduction (JECAR), 2:4 (09 Mar 2005) (Open Access). DOI: 10.1186/1743-1050-2-4
PubMed   pdf-download (1.60 MB)

HENEWEER, C., DENKER, H.-W., THIE, M.:
Uterine epithelial cells require special phenotype plasticity for trophoblast adhesion.
(Abstr.) Verh. Anat. Ges. 99 (Ann. Anat./Anat. Anz. 186), 195 (2004).
pdf-download (330 KB)

HENEWEER, C., DENKER, H.-W., THIE, M.:
Cellular dynamics of actin cytoskeleton in RL95-2 cells during trophoblast binding:
a high resolution confocal microscopy study on Rho protein regulation.

26. Jahrestagung der Deutschen Gesellschaft für Zellbiologie (DGZ), Bonn, 26.-29. März 2003.
(Abstr.) Eur. J. Cell Biol. 82 (Suppl. 53): 75-76, 2003.
pdf-download (302 KB)

THIE, M., HENEWEER, C., KRUSE, L.H., DENKER, H.-W.:
Cellular dynamics of human uterine epithelial RL95-2 cells during trophoblast binding:
a high resolution confocal microscopy study on Rho protein regulation.

(Abstr.) Verh. Anat. Ges. 98; Anat. Anz./Ann. Anat. 185 (Suppl.): 141-142, 2003.
pdf-download (412 KB)

HENEWEER, C., ADELMANN, H.G., KRUSE, L.H., DENKER, H.-W., THIE, M.:
Human Uterine Epithelial RL95-2 Cells Reorganize Their Cytoplasmic Architecture with Respect to Rho Protein and F-Actin in Response to Trophoblast Binding.
Cells Tissues Organs 175: 1-8 (2003). PubMed   pdf-download (180 KB)

HOHN, H.-P., DONNER, A.J. and DENKER, H.-W.:
Endometrial receptivity: Selective adhesion competence of rabbit uterine epithelium for trophoblast but not for various tumor cells.
Cells Tissues Organs 173: 204-216 (2003). PubMed   pdf-download (720 KB)

DENKER, H.-W. (ed.):
Molecular Approaches to Cell-Cell Adhesion: From Leukocyte Extravasation to Embryo Implantation.
Basel etc.: S. Karger AG, 2002 (=Cells Tissues Organs, Vol. 172, No. 3, pp. 147-254, 2002; ISBN 3-8055-7532-7, ISSN 1422-6405).
Contents pdf-download (30.6 KB)   Karger Verlag   Online Access   German National Library

THIE, M. and DENKER, H.-W.:
In vitro studies on endometrial adhesiveness for trophoblast: cellular dynamics in uterine epithelial cells.
Cells Tissues Organs 172: 237-252 (2002). PubMed   pdf-download (835 KB)

HOHN, H.-P. and DENKER, H.-W.:
Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells.
Cells Tissues Organs 172: 218-236 (2002). PubMed   pdf-download (391 KB)

HENEWEER, C., KRUSE, L.H., KINDHÄUSER, F., SCHMIDT, M., JAKOBS, K.H., DENKER, H.-W. and THIE, M.:
Adhesiveness of human uterine epithelial RL95-2 cells to trophoblast: Rho protein regulation.
Molecular Human Reproduction 8: 1014-1022 (2002). PubMed   pdf-download (2.01 MB)

DENKER, H.-W. and THIE, M.:
The regulatory function of the uterine epithelium for trophoblast attachment: experimental approaches.
In: Molecular, Cellular and Developmental Biology of Reproduction: Basic and Clinical Aspects (P.M. Motta, S.A. Nottola, G. Macchiarelli and S. Correr, Eds.).
Italian Journal of Anatomy and Embryology 106 (2 Supplement 2): 291-306, 2001.
pdf-download (12.2 MB) PubMed

THIE, M., TINEL, H., DENKER, H.-W.:
Calcium influx in human uterine epithelial RL95-2 cells is required for trophoblastlike JAR cell binding-signaling mechanisms in an embryo implantation model.
(Abstr.) 17. Arbeitstagung der Anatomischen Gesellschaft, Würzburg, 27.09.-29.09.2000. Verh. Anat. Ges. 96; Ann. Anat. 183 (Suppl.) 177-178, 2001.
pdf-download (439 KB)

THIE, M., TINEL, H., DENKER, H.-W.:
The role of calcium influx on apical adhesiveness of human uterine epithelial RL95-2 cells for trophoblast-like JAR cells.
(Abstr.) 24. Annual Meeting of the German Society for Cell Biology, Karlsruhe, March 27-31, 2000. Eur J Cell Biol 79 (Suppl 50): p. 52 (2000).
pdf-download (485 KB)

DENKER, H.-W, Thie, M., Tinel, H.:
Verfahren und Vorrichtung zur diagnostischen Bestimmung der Rezeptivität des Uterusepithels. Method and Device for Diagnostically Detecting the Receptivity of the Uterus Epithelium.
Patentschrift, Int. Veröffentlichungsnr. (PCT): WO 01/72229 A1. 2001.

DENKER, H.-W, Thie, M., Tinel, H.:
Verfahren und Vorrichtung zur diagnostischen Bestimmung der Rezeptivität des Uterusepithels.
Anmelder: Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V., München. Patentschrift, BRD, Nr. DE 100 14 350 A1; PCT WO 01/72229 A1/DE01/01061. 2001.

TINEL, H., DENKER, H.-W. and THIE, M.:
Calcium influx in human uterine epithelial RL95-2 cells triggers adhesiveness for trophoblast-like cells. Model studies on signalling events during embryo implantation.
Molecular Human Reproduction 6: 1119-1130 (2000). PubMed   pdf-download (1.00 MB)

HOHN, H.-P., LINKE, M. and DENKER, H.-W.:
Adhesion of trophoblast to uterine epithelium as related to the state of trophoblast differentiation: in vitro studies using cell lines.
Mol. Reprod. Dev. 57: 135-145 (2000). PubMed   pdf-download (33.0 MB)

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THIE, M, SCHMIDT M, DENKER H.-W.:
Trophoblast-type cell adhesion to human uterine epithelial RL95-2 cells is dependent on Rho-regulated mechanisms.
(Abstr.) Verh. Anat. Ges. 95; Ann. Anat. 182 (Suppl), 120-121, 1999.

THIE, M., DENKER H.-W.:
REM/AFM Untersuchungen an der freien Oberfläche von menschlichen Uterusepithelzellen - neue Einsichten in die Trophoblast-Uterusepithel-Interaktion in der Einleitungsphase der Embryo-Implantation.
(Abstr.) 29. Tagung der Deutschen Gesellschaft für Elektronenmikroskopie, Dortmund, 5.-10.09.1999. Eur J Cell Biol 78 (Suppl 50): 18 (1999).

THIE, M, DENKER, H.-W.:
Adhesiveness of the apical membrane of uterine epithelial cells: a cascade of molecular alterations that leads to stable cell-cell binding.
(Abstr.) 23. Annual Meeting of the DGZ, Rostock, March 14-18, Europ. J. Cell Biol. 78, (Suppl. 49), 24 (1999).
pdf-download (467 KB)

THIE, M, DENKER, H.-W.:
Staurosporine, a protein kinase C inhibitor, causes down-regulation of the epithelial phenotype in human endometrial HEC-1-A cells and induces adhesiveness for trophoblast.
(Abstr.) Verh. Anat. Ges. 94, Annals of Anatomy 181, Suppl., 217-218 (1999).
pdf-download (471 KB)

DENKER, H.-W., THIE, M.:
Studies on the regulatory function of the uterine epithelium for trophoblast attachment.
(Abstr.) XV Congress of I.F.A.A., 4th International Malpighi Symposium; Rome 1999. Ital. J. Anat. Embryol 104 (Suppl. 1), 140 (1999).
pdf-download (620 KB)

THIE, M.; RÖSPEL, R.; DETTMANN, W.; BENOIT, M.; LUDWIG, M.; GAUB, H.E. and DENKER, H.-W.:
Interactions between trophoblast and uterine epithelium:
monitoring of adhesive forces.

Human Reproduction 13, 3211-3219 (1998). PubMed   pdf-download (471 KB)

THIE, M, DENKER H.-W.:
A protein kinase C mediated signaling pathway as a link between modulation of the epithelial phenotype and induction of apical adhesiveness in human uterine cells?
(Abstr.) 2. Joint Meeting „Signal Transduction: Receptors, Mediators and Genes“, Paul-Ehrlich-Institut, Langen, 19.-21.11.1998. Program and Abstracts, p. 85 (P40) (1998)

THIE, M, DETTMANN W, RÖSPEL R, BENOIT M, LUDWIG M, GAUB HE, DENKER H.-W:
Adhesion forces between confronted epithelia: uterine epithelium and trophoblast.
(Abstr.) 22. Jahrestagung der Deutschen Gesellschaft für Zellbiologie, Saarbrücken, 15.-19.03.1998, Eur J Cell Biol 75 (Suppl 48): 14 (1998)

THIE, M., RÖSPEL, R., DETTMANN, W., BENOIT, M., LUDWIG, M., GAUB, H.W. DENKER, H.-W.:
Attachment of trophoblast to unterine epithelium: direct measurements of adhesive forces with the atomic force microscope (AFM)
(Abstr.) Verh. Anat. Ges. 93, Anat. Anz./Annals of Anatomy 180, Suppl., 224-225 (1998)

THIE, M., HERTER, P., POMMERENKE, H., DÜRR, F., SIECKMANN, F., NEBE, B., RYCHLY, J. and DENKER, H.-W.:
Adhesiveness of the free surface of a human endometrial monolayer for trophoblast as related to actin cytoskeleton.
Molecular Human Reproduction 3, 275-283 (1997). PubMed   pdf-download (607 KB)

THIE, M. and DENKER, H.-W.:
Endometrial receptivity for trophoblast attachment: Model studies using cell lines.
In: Microscopy for Reproduction and Development: A Dynamic Approach (P.M. Motta, ed.). Antonio Delfino Editore, Rome, 1997, pp. 241-249. pdf-download (30.0 MB)

BIERMANN, L.; GABIUS, H.-J. and DENKER, H.-W.:
Neoglycoprotein-binding sites (endogenous lectins) in the Fallopian tube, uterus and blastocyst of the rabbit during the preimplantation phase and implantation.
Acta Anat. 160, 159-171 (1997). PubMed   pdf-download (24.3 MB)

THIE, M., FUCHS, P., BUTZ, S., SIECKMANN, F., HOSCHÜTZKY, H., KEMLER, R., DENKER, H.-W.:
Adhesiveness of the apical surface of uterine epithelial cells:
the role of junctional complex integrity.

Europ. J.Cell Biol. 70, 221-232 (1996). PubMed   pdf-download (7.88 MB)

THIE, M., FUCHS, P., DENKER, H.-W.:
Epithelial cell polarity and embryo implantation in mammals.
Int. J. Dev. Biol. 40, 389-393 (1996). PubMed   pdf-download (1.81 MB)

THIE, M., FUCHS, P., SIECKMANN, F., DENKER, H.-W.:
Implantation model studies: integrins and adhesiveness of the apical cell pole of RL 95-2, a human uterine epithelial cell line.
(Abstr.) 12th Annual Meeting, European Soc. of Human Reprod. and Embryol., Maastricht 1996. Human Reprod. 11, Abstract Book I, 123 (1996)
pdf-download (405 KB)

THIE, M., FUCHS, P., BUTZ, S., HOSCHÜTZKY, H., SIECKMANN, F., DENKER, H.-W.:
Adhesiveness of the apical plasma membrane for trophoblast correlates with loss of epithelial-type organization of the junction-cytoskeletton complex in a human uterine epithelial cell line, RL 95-2. (Abstr.)
(Abstr.) Verh. Anat. Ges. 91 (Ann. Anat. / Anat. Anz., Suppl. 178), 250-251 (1996)

THIE, M., HARRACH-RUPRECHT, B., SAUER, H., FUCHS, P., ALBERS, A., DENKER, H.-W.:
Cell adhesion to the apical pole of epithelium: a function of cell polarity.
Europ. J.Cell Biol. 66, 180-191 (1995). PubMed   pdf-download (8.49 MB)

ALBERS, A., THIE, M., HOHN, H.-P., DENKER, H.-W.:
Differential expression and localization of integrins and CD44 in the membrane domains of human uterine epithelial cells during the menstrual cycle.
Acta Anatomica 153, 12-19 (1995). PubMed   pdf-download (15.3 MB)

HOHN, H.-P., HUCH, G., TLOLKA, U., DENKER, H.-W.:
Differential Expression of CD44 in rabbit uterine epithelium during early pregnancy.
Acta Anatomica 152, 185-194 (1995). PubMed   pdf-download (16.8 MB)

DENKER, H.-W.:
Cell biological views of embryo implantation (A Review).
Turkish J. of Medical Sciences, Suppl., 1-12 (1995). pdf-download (29.1 MB)

THIE, M., FUCHS, P., ALBERS, A., DENKER, H.-W.:
Polar organization of uterine epithelial cells and embryo implantation.
(Abstr.) Verh. Anat. Ges. 90 (Anat. Anz., Suppl.177), 23-24 (1995)
pdf-download (320 KB)

HOHN, H.-P., HUCH, G., TLOLKA, U., DENKER, H.-W.:
Differential expression of CD44 in rabbit uterine epithelium during early pregnancy.
(Absr.) Verh. Anat. Ges. 90 (Ann. Anat. 177, Suppl.), 25 (1995)
pdf-download (366 KB)

DENKER, H.-W., FUCHS, P., ALBERS, A., THIE, M.:
Uterine epithelial cell polarity and adhesiveness for trophoblast: in-vitro model studies using cell lines.
(Abstr.) Society of Reproduction, 28th Annual Meeting, Davis, CA, 1995. Biol. Reprod. 52, Suppl. 1, 162 (1995)
pdf-download (319 KB)

DENKER, H.-W.:
Endometrial receptivity: Cell biological aspects of an unusual epithelium. A review.
Ann. Anat. 176, 53-60 (1994). PubMed   pdf-download (5.57 MB)

GRÜMMER, R., HOHN, H.-P., MAREEL, M.M., DENKER, H.-W.:
Adhesion and invasion of three human choriocarcinoma cell lines into human endometrium in a three-dimensional organ culture system.
Placenta 15, 411-429 (1994). PubMed

THIE, M., ALBERS, A., and DENKER, H.-W.:
Endometrial receptivity: cell biological aspects.
In: Mori, T., Aono, T., Tominaga, T. and Hiroi, H. (eds.): Perspectives on Assisted Reproduction (Serono Symposia Series "Frontiers in Endocrinology", Vol. 4). Ares-Serono Symposia, Christengraf, Rome, 1994, pp. 331-337. pdf-download (2.98 MB)

DENKER, H.-W.:
Cell biology of endometrial receptivity and of trophoblast-endometrial interactions.
In: Endocrinology of Embryo-Endometrium Interactions (S.R. Glasser, J. Mulholland and A. Psychoyos, eds.) New York: Plenum Press, 1994, pp. 17-32. DOI: 10.1007/978-1-4615-1881-5_3
SpringerLink   pdf-download (26.8 MB, with kind permission of Springer Science and Business Media)

THIE, M., ALBERS, A., DENKER, H.-W.:
Expression von Integrinen in Uterus-Epithelzellen in Relation zur Phänotypmodulation.
Verh. Anat. Ges. 89 (Ann. Anat., Suppl.) 176, 225-226 (1994)
pdf-download (479 KB)

DENKER, H.-W.:
Implantation: A cell biological paradox.
J. Exp. Zool. 266, 541-558 (1993). PubMed   pdf-download (75.9 MB)

JOHN, N.J., LINKE, M., DENKER, H.-W.:
Retinoic acid decreases attachment of JAR choriocarcinoma spheroids to a human endometrial cell monolayer in vitro.
Placenta 14, 13-24 (1993). PubMed

THIE, M., ALBERS, A., FUCHS, P., DENKER, H.-W.:
Integrins in the human endometrial cell lines, RL95-2 and AN3 CA.
(Abstr.) Journal of Reproduction and Fertility, Abstract Series, No. 12, December 1993. Society for the Study of Fertility & German Society for the Study of Fertility and Sterility, Winter Meeting, Aachen, Dec. 1993
pdf-download (448 KB)

HOHN, H.-P., LINKE, M., DENKER, H.-W.:
Modulation of differentiation in choriocarcinoma cells also modulates adhesion to endometrial cells in an in-vitro-model.
(Abstr.) Verh. Anat. Ges., 88. Versammlung in Düsseldorf (Ann. Anat. 175, Suppl.), 86-87 (1993)
pdf-download (380 KB)

HOHN, H.-P., LINKE, M., DENKER, H.-W.:
Induction of differentiation in choriocarcinoma cells modulates elements of invasiveness in in-vitro-models.
(Abstr.) J. Cancer Res. Clin. Oncol. 119, (Suppl. 2), 86 (1993)
pdf-download (692 KB)

LINKE, M., HOHN, H.-P., JOHN, N.J., DENKER, H.-W.:
Modulation of differentiation alters the adhesive behaviour of choriocarcinoma cells.
(Abstr.) Europ. J. Cell Biol. 60, (Suppl. 37), 17 (1993)
pdf-download (467 KB)

THIE, M., ALBERS, A., DENKER, H.-W.:
Expression and localization of integrins in human uterine epithelial cells.
(Abstr.) 8th World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, Kyoto, Japan, 1993. Journal of Assisted Reproduction and Genetics 10 No. 6 (Suppl.), 238 (1993)
pdf-download (603 KB)

DENKER, H.-W.:
Endometrial receptivity and trophoblast invasiveness: Cell biological aspects.
(Abstr.) 8th World Congress on In Vitro Fertilization and Alternate Assisted Reproduction, Kyoto, Japan, 1993. Journal of Assisted Reproduction and Genetics 10 No. 6 (Suppl.), 29 (1993)
pdf-download (697 KB)

HOHN, H.-P., LINKE, M., JOHN, N., and DENKER, H.-W.:
Induction of differentiation reduces cell adhesion of choriocarcinoma cells in an in vitro model. (Abstr.)
(Abstr.) Clin. Exptl. Metastasis, Vol. 10, Suppl. 1, 39 (1992)

DENKER, H.-W.:
Cell biology of endometrial receptivity and of trophoblast-endometrial interactions: recent aspects.
(Abstr.) Sympos. on Endocrinology of Embryo-Endometrial Interactions (Satellite Sympos. of the Ninth International Congress of Endocrinol., N.I.C.E. 92), Bordeaux 1992, Abstr. No. S 1.
pdf-download (272 KB)

DONNER, A., BEHRENS, J., FRIXEN, U., and DENKER, H.-W.:
Uvomorulin, actin and the shift in uterine epithelial polarity at embryo implantation.
(Abstr.) Ann. Meet. Deutsche Ges. Zellbiol., Konstanz 1992. Europ. J. Cell Biol. Suppl. 36 (Vol. 57), 16 (1992)
pdf-download (478 KB)   poster (9.15 MB)

DONNER, A., HOHN, H.-P. und DENKER, H.-W.:
Selektive Rezeptivität des Endometriums für Trophoblast-Invasion in einem Organkultur-Modell.
(Abstr.) Verh. Anat. Ges. 85 (Anat. Anz. Suppl. 170), 593-594 (1991)
pdf-download (563 KB)

DENKER, H.-W.:
Das Implantationsfenster: Zellbiologische Grundlagen der Invasivität des Trophoblasten und der Rezeptivität des Endometriums.
(Abstr.) Dreiländertagung „Fertilität und Sterilität“ der Deutschen Gesellschaft zum Studium der Sterilität und Fertilität, gemeinsam mit der Österreichischen Gesellschaft zum Studium der Sterilität und Fertilität und der Schweizerischen Gesellschaft für Fertilität und Sterilität, Goslar 1991, Zusammenfassender Bericht (Alete Wissenschaftlicher Dienst) pp. 36-38
pdf-download (856 KB)

DONNER, A., CLASSEN-LINKE, I., FRIXEN, U., BEHRENS, J. und DENKER, H.-W.:
Änderungen im Verteilungsmuster von Markerproteinen für das basolaterale Membran-Kompartiment des Uterusepithels in der Periimplantationsphase: Desmoplakin und Uvomorulin.
(Abstr.) 8. Arbeitstagung d. Anat. Ges., Würzburg 1990 Anat. Anz., Jena 172, 33 (1991)
pdf-download (393 KB)   poster (13.3 MB)

WINTERHAGER, E., MARX, M. und DENKER, H.-W.:
Strukturelle Veränderungen der Basallamina des Uterusepithels des Kaninchens in Vorbereitung auf die Trophoblastinvasion.
(Abstr.) Verh. Anat. Ges. 84 (Anat. Anz. Suppl. 168), 41-42 (1991)
pdf-download (665 KB)

DENKER, H.-W. and APLIN, J.D. (eds.):
Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation.
New York and London: Plenum Medical Book Com., 1990 (=Trophoblast Research, Vol. 4).
pdf-download (20.2 MB)   SpringerLink

DENKER, H.-W.:
Trophoblast-endometrial interactions at embryo implantation: A cell biological paradox.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 3-29.
pdf-download (29.9 MB, with kind permission of Springer Science and Business Media)   SpringerLink

HOHN, H.-P. and DENKER, H.-W.:
A three-dimensional organ culture model for the study of implantation of rabbit blastocyst in vitro.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 71-95.
pdf-download (35.8 MB, with kind permission of Springer Science and Business Media)   SpringerLink

GRÜMMER, R., HOHN, H.-P. and DENKER, H.-W.:
Choriocarcinoma cell spheroids: An in vitro model for the human trophoblast.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 97-111.
pdf-download (19.7 MB, with kind permission of Springer Science and Business Media)   SpringerLink

BÜKERS, A., FRIEDRICH, J., NALBACH, B.P. and DENKER, H.-W.:
Changes in lectin binding patterns in rabbit endometrium during pseudopregnancy, early pregnancy and implantation.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 285-305.
pdf-download (26.7 MB, with kind permission of Springer Science and Business Media)   SpringerLink

CLASSEN-LINKE, I. and DENKER, H.-W.:
Preparation of rabbit uterine epithelium for trophoblast attachment: Histochemical changes in the apical and lateral membrane compartment.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 307-322.
pdf-download (30.5 MB, with kind permission of Springer Science and Business Media)   SpringerLink

WINTERHAGER, E. and DENKER, H.-W.:
Changes in lipid organization of uterine epithelial cell membranes at implantation in the rabbit.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 323-338.
pdf-download (23.6 MB, with kind permission of Springer Science and Business Media)   SpringerLink

HOCHFELD, A., BEIER, H.M. and DENKER, H.-W.:
Changes of intermediate filament protein localization in endometrial cells during early pregnancy of rabbits.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 357-374.
pdf-download (31.2 MB, with kind permission of Springer Science and Business Media)   SpringerLink

MARX, M., WINTERHAGER, E. and DENKER, H.-W.:
Penetration of the basal lamina by processes of uterine epithelial cells during implantation in the rabbit.
In: Trophoblast Invasion and Endometrial Receptivity. Novel Aspects of the Cell Biology of Embryo Implantation. (H.-W. Denker and J.D. Aplin, eds.) (Trophoblast Research, Vol. 4). New York and London: Plenum Medical Book Comp., 1990, pp. 417-430.
pdf-download (28.1 MB, with kind permission of Springer Science and Business Media)   SpringerLink

BÜKERS, A. und DENKER, H.-W.:
Lektinhistochemische Charakterisierung von Kaninchenendometrium in vivo und in vitro - eine vergleichende Studie.
Verh. Anat. Ges. 83 (Anat. Anz. Suppl. 166), 415-416 (1990).
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WINTERHAGER, E., CLASSEN-LINKE, I. und DENKER, H.-W.:
Strukturelle Veränderungen der apikalen Uterusepithelzellmembran in Vorbereitung auf die Embryoimplantation.
Verh. Anat. Ges. 83 (Anat. Anz. Suppl. 166), 153-154 (1990)
pdf-download (541 KB)

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DENKER, H.-W., HOHN, H.-P. and BÜKERS, A.:
Investigations on the cell biology of embryo implantation.
In: Reproductive Biology and Medicine (A.F. Holstein, K.D. Voigt and D. Grässlin, eds.) Berlin: Diesbach Verlag 1989, pp. 224-238. pdf-download (32.4 MB)

HOHN, H.-P., WINTERHAGER, E., BUSCH, L.C., MAREEL, M.M. and DENKER, H.-W.:
Rabbit endometrium in organ culture: Morphological evidence for progestational differentiation in vitro.
Cell Tissue Res. 257, 505-518 (1989). PubMed

MITCHELL, J.A. and DENKER, H.-W.:
Implantation-induced changes in uterine arylamidase localization in the rabbit, rat, hamster and guinea-pig.
J. Reprod. Fert. 83, 355-364 (1988).
PubMed   Reproduction pdf-download

CLASSEN-LINKE, I., DENKER, H.-W.:
Membrane changes of uterine epithelium in preparation for trophoblast attachment as indicated by membrane-bound enzymes.
(Abstr.) Fourth International Congress of Cell Biology, Montreal (Canada), August 14-19 (1988).
pdf-download (762 KB)

WINTERHAGER, E., BRÜMMER, F., DERMIETZEL, R., HÜLSER, D.F. and DENKER, H.-W.:
Gap junction formation in rabbit uterine epithelium in response to embryo recognition.
Dev. Biol. 126, 203-211 (1988). PubMed   PDF (German National Library)

DENKER, H.-W.:
Implantation: Recent approaches to understand a cell biological paradox.
In: Human Reproduction. Current Status/Future Prospect (Proceed. VIth World Congr. on Human Reproduction, Tokyo 1987) (R. Iizuka and K. Semm, eds.) Amsterdam, etc.: Excerpta Medica, Elsevier Science Publ. (International Congress Series Nr. 768), 1988, pp. 237-240. pdf-download (1.86 MB)

WINTERHAGER, E., LEISER, R., DENKER, H.-W.:
Lipiddomänen der Plasmamembran im Uterusepithel von Kaninchen zum Zeitpunkt der Implantation. Eine gefrierbruch-zytochemische Untersuchung.
XXXVII Sympos. Ges. f. Histochemie, Gargellen 1986. Acta histochem., Suppl. 36, 395-398 (1988). PubMed

BÜKERS, A., HOHN, H.-P., DENKER, H.-W.:
Lectin histochemical evaluation of an in-vitro model for trophoblast invasion.
(Abstr.) International Symposium "Lectins and Glycoconjugates in Oncology. Structure, Function, Clinical Application", Göttingen / FR Germany, 4-5 December 1987.
pdf-download (925 KB)

CLASSEN-LINKE, I., DENKER, H.-W. and WINTERHAGER, E.:
Apical plasma membrane-bound enzymes of rabbit uterine epithelium: Pattern changes during the periimplantation phase.
Histochemistry 87, 517-529 (1987). PubMed   pdf-download (5.97 MB, with kind permission of Springer, Heidelberg)

MITCHELL, J.A., DRIESSEN, G., SCHEIDT, H. and DENKER, H.-W.:
Changes in intraconceptus pressure in the rabbit during days 7 - 10 of pregnancy.
Biol. Reprod. 36, 669-675 (1987). PubMed   pdf-download (1.11 MB)

WINTERHAGER, E., DERMIETZEL, R., BRÜMMER, F. und DENKER, H.-W.:
Immunhistochemischer Nachweis des 26k-Proteins der gap junctions im Uterusepithel des Kaninchens in Abhängigkeit von der Reproduktionsphase.
Verh. Anat. Ges. 81 (Lübeck 1986), Anat. Anz. Suppl. 162, 503-504 (1987). pdf-download (881 KB)

MARX, M., WINTERHAGER, E. and DENKER, H.-W.:
Penetration of the basal lamina by processes of uterine epithelial cells precedes trophoblast invasion during implantation in the rabbit.
(Abstr.) 8th European Anatomical Congress, Antwerp, Sept. 1987. Acta Anat. 130, 59 (1987)
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MARX, M., WINTERHAGER, E. and DENKER, H.-W.:
Changes in the basal lamina structure of the uterine epithelium at implantation.
(Abstr.) Ann. Meet. Deutsche Ges. Zellbiologie, Heidelberg 1987. Europ. J. Cell. Biol. 43 , Suppl. 17, 36 (1987)
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CLASSEN-LINKE, I. and DENKER, H.-W.:
Stage-specific changes in apical plasma membrane-bound enzymes of rabbit uterine epithelium during the periimplantation phase.
(Abstr.) Ann. Meeting Deutsche Ges. Zellbiologie, Heidelberg 1987. Europ. J. Cell Biol. 43, Suppl. 17, 10 (1987)
pdf-download (346 KB)

HOHN, H.-P., DONNER, A. and DENKER, H.-W.:
Specific receptivity of rabbit endometrium for attachment of trophoblast but not of tumor cells in vitro.
(Abstr.) J. Cell Biol. 105, 306a (1987)
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DENKER, H.-W.:
Implantation: recent approaches to understand a cell biological paradox.
(Abstr.) VIth World Congress on Human Reproduction, Tokyo 1987, p. 26
pdf-download (342 KB)

DENKER, H.-W.:
Epithel-Epithel-Interaktionen bei der Embryo-Implantation: Ansätze zur Lösung eines zellbiologischen Paradoxons. (Hauptreferat).
Verh. Anat. Ges. 80 (Prag 1985), Anat. Anz. Suppl. 160, 93-114 (1986).
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HOHN, H.-P., DONNER, A. and DENKER, H.-W.:
Evaluation of an in vitro model for embryo implantation: selective receptivity of rabbit endometrium for trophoblast attachment.
(Abstr.) 24th Annual Meeting of the Cell, Tissue and Organ Culture Study Group (C.T.O.C.), Heidelberg 1986, p. 9

WINTERHAGER, E., BRÜMMER, F., DERMIETZEL, R. and DENKER, H.-W.:
Induction of cell coupling via gap junctions in the uterine epithelium of the rabbit prior to trophoblast invasion.
(Abstr.) 24th Annual Meeting of the Cell, Tissue and Organ Culture Study Group (C.T.O.C.) , Heidelberg 1986, p. 18
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CLASSEN-LINKE, I. and DENKER, H.-W.:
Preparation of uterine epithelium for trophoblast attachment: changes in apical plasma membrane-bound enzymes.
(Abstr.) 24th Annual Meeting of the Cell, Tissue and Organ Culture Study Group (C.T.O.C.) conjoint with the 37th Meeting of the European Tissue Culture Society (ETCS), Heidelberg 1986. Europ. J. Cell Biol. 42, Suppl. 15, 69 (1986)
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MARX, M., WINTERHAGER, E. and DENKER, H.-W.:
Fine structural changes in the basal lamina of the uterine epithelium in preparation for trophoblast invasion.
(Abstr.) 24th Annual Meeting of the Cell, Tissue and Organ Culture Study Group (C.T.O.C.) conjoint with the 37th Meeting of the European Tissue Culture Society (ETCS), Heidelberg 1986. Europ. J. Cell Biol. 42, Suppl. 15, 71 (1986)
pdf-download (343 KB)

WINTERHAGER, E., BRÜMMER, F. und DENKER, H.-W.:
Induktion von gap junctions im Uterusepithel gravider Kaninchen.
(Abstr.) 5. Arbeitstagung d. Anat. Ges., Würzburg 1985. Anat. Anz. 161, 176-177 (1986)
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HOHN, H.-P. and DENKER, H.-W.:
Confrontation of blastocysts and endometrium in organ culture: towards an in-vitro model for embryo implantation.
Abstract No. 147, 1st Meeting of the Europ. Soc. of Human Reproduction and Embryology, Bonn 1985. Human Reprod. 1 (Suppl. 1), 49-50 (1986)
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DENKER, H.-W., DONNER, A. and HOHN, H.-P.:
Interaction of trophoblast and of tumor cells with endometrial fragments in organ culture.
(Abstr.) 23. Annual Meeting of the Cell, Tissue and Organ Culture Study Group (C.T.O.C.), Kollekolle (Denmark) 1985
pdf-download (706 KB)

WINTERHAGER, E., BRÜMMER, F. and DENKER, H.-W.:
Gap junction formation in the uterine epithelium in response to embryo recognition.
(Abstr.) Annual Meeting Belgian Soc. Cell Biol./ German Soc. Cell Biol., Bonn 1985. Europ. J. Cell Biol. 36, Suppl. 7, 74 (1985)
pdf-download (315 KB)

HOHN, H.-P. and DENKER, H.-W.:
Attachment and invasion of rabbit blastocysts confronted with endometrium in organ culture.
(Abstr.) Annual Meeting Belgian Soc.Cell Biol./German Soc. Cell Biol., Bonn 1985. Europ. J. Cell Biol. 36, Suppl. 7, 28 (1985)
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DENKER, H.-W.:
Embryo implantation: controlled invasion of a non-tumor tissue.
(Abstr.) Annual Meeting Belgian Soc. Cell Biol. / German Soc. Cell Biol., Bonn 1985. Europ. J. Cell Biol. 36, Suppl. 7, 15 (1985)
pdf-download (325 KB)

BRÜMMER, F., WINTERHAGER, E., DENKER, H.-W. and HÜLSER, D.F.:
Cell-cell communication via gap junctions in rabbit uterine epithelium related to implantation.
(Abstr.) Annual Meeting Belgian Soc. Cell Biol. /German Soc. Cell Biol., Bonn 1985. Europ. J. Cell Biol. 36, Suppl. 7, 11 (1985)
pdf-download (301 KB)

WINTERHAGER, E., DERMIETZEL, R., BRÜMMER, F. and DENKER, H.-W.:
Gap junction formation in rabbit uterine epithelium during the periimplantation phase.
(Abstr.) Ann. Meet. Deutsche Ges. Zellbiologie, Tübingen 1986. Europ. J. Cell Biol. 39, Suppl. 12, 37 (1985)
pdf-download (294 KB)

HOHN, H.-P., DONNER, A. and DENKER, H.-W.:
Evaluation of an in vitro model for embryo implantation: Selective receptivity of rabbit endometrium for trophoblast attachment.
(Abstr.) Ann. Meet. Deutsche Ges. Zellbiologie, Tübingen 1986. Europ. J. Cell Biol. 39, Suppl. 12, 18 (1985)
pdf-download (344 KB)

WINTERHAGER, E., KÜHNEL, W. and DENKER, H.-W.:
Proliferation of tight junctions and fusion in uterine epithelial cells of the rabbit.
(Abstr.) Annual Meeting, Deutsche Ges. Zellbiologie, Marburg 1984. Europ. J. Cell Biol. 33, Suppl. 5, 38 (1984)
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WINTERHAGER, E. und DENKER, H.-W.:
Unterschiedliche Membrandifferenzierung im Uterusepithel gravider und pseudogravider Kaninchen während der Periimplantationsphase.
In: Physiologie und Pathologie der Fortpflanzung. Verhandlungsbericht, IX. Veterinär-Humanmedizinische Gemeinschaftstagung, Deutsche Gesellschaft zum Studium der Fertilität und Sterilität, Hannover 1984 (K. Semm, J. Hahn, H. Merkt, E. Grunert, L. Mettler, eds.) pp. 136-139 (Abstr. in: Zuchthygenie 19, 117, 1984)
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DENKER, H.-W.:
Basic aspects of ovoimplantation.
In: Obstetrics and Gynecology Annual (Ralph M. Wynn, ed.) Vol. 12. Norwalk/Connecticut, Appleton-Century-Crofts, 1983, pp. 15-42. PubMed   pdf-download (12.0 MB)

MITCHELL, J.A., DRIESSEN, G., SCHEIDT-BLEICHERT, H. and DENKER, H.-W.:
Measurement of pressure changes in rabbit conceptus 7 to 10 days post coitum.
Abstract No. 68A, Annual Conference of the Society for the Study of Fertility, Manchester 1983
pdf-download (261 KB)

MITCHELL, J.A., DRIESSEN, G., SCHEIDT-BLEICHERT, H. and DENKER, H.-W.:
Pressure changes in rabbit conceptus 7 to 10 days post coitum.
(Abstr.) 16th Annual Meet. Soc. for the Study of Reproduction, Cleveland (Ohio) 1983. Biol. Reprod. 28, Suppl. 1, 140 (1983)
pdf-download (408 KB)

NALBACH, B.P. and DENKER, H.-W.:
Stage-dependent changes in lectin binding patterns in rabbit uterus and blastocyst during the preimplantation period and implantation.
(Abstr.) 4th Sympos. on Lectins in Cell Biology and Medicine, Cologne 1983. Europ. J. Cell Biol., Suppl. 4, 13 (1983)
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DENKER, H.-W.:
Embryo implantation and trophoblast invasion.
In: Cell Movement and Neoplasia (M. De Brabander et al., eds.) Oxford/New York: Pergamon Press, 1980, pp. 151-162.
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VAN HOORN, G. and DENKER, H.-W.:
Effect of the blastocyst on a uterine amino acid arylamidase in the rabbit.
J. Reprod. Fert. 45, 359-362 (1975).
PubMed   Reproduction pdf-download

DENKER, H.-W.:
Enzym-Topochemie von Frühentwicklung und Implantation des Kaninchens. II. Glykosidasen.
Histochemie 25, 268-285 (1971). PubMed   pdf-download (2.32 MB, with kind permission of Springer, Heidelberg)

DENKER, H.-W.:
Topochemie hochmolekularer Kohlenhydratsubstanzen in Frühentwicklung und Implantation des Kaninchens.
II. Beiträge zu entwicklungsphysiologischen Fragestellungen.

Zool. Jb. Physiol. 75, 246-308 (1970). pdf-download (23.1 MB)

DENKER, H.-W.:
Topochemie hochmolekularer Kohlenhydratsubstanzen in Frühentwicklung und Implantation des Kaninchens.
I. Allgemeine Lokalisierung und Charakterisierung hochmolekularer Kohlenhydratsubstanzen in frühen Embryonalstadien.

Zool. Jb. Physiol. 75, 141-245 (1970). pdf-download (29.6 MB)

DENKER, H.-W.:
Zur Enzym-Topochemie von Frühentwicklung und Implantation des Kaninchens.
Dissertation, Medizinische Fakultät der Philipps-Universität, Marburg/Lahn 1970. German National Library

DENKER, H.-W.:
Topochemie hochmolekularer Kohlenhydratsubstanzen in Frühentwicklung und Implantation des Kaninchens.
Dissertation, Naturwissenschaftliche Fakultät der Philipps-Universität, Marburg/Lahn 1969. German National Library

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