Embryo Implantation I: Proteinases
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Overview
Main findings:
- Discovery and characterisation of blastolemmase, a trophoblast-dependent serine proteinase, in the rabbit.
- Identification of a key role of blastolemmase in the process of shedding of blastocyst coats (zona pellucida and its equivalents) at implantation initiation (hatching enzyme). Implantation initiation can be blocked experimentally by intra-uterine application of certain non-toxic proteinase inhibitors in vivo in the rabbit, without preventing continuing differentiation of the blastocyst. The latter remains free (non-attached) within the uterine lumen but nevertheless continues developing and forming the basic body plan.
- These findings provide experimental proof that formation of the body axes and of the basic body plan does not depend on embryo implantation. It thus contradicts a hypothesis (derived from certain observations in the mouse) that had been postulating just this.
- Biological interest: These experiments are one of the rare examples where a very specific effect can be obtained in a complex biological system without major side-effects being observed: In this case development of the embryo proper (which is known to react very sensitively to any non-specific, e.g. toxic, side-effects) goes on.
- Ethical aspects: On the other hand it must be concluded from these experiments that any application of such a proteinase inhibition concept in human contraception cannot be accepted for ethical reasons.
- Comparative studies on related proteinases associated with embryo implantation in other species (rodents, cat, horse, tammar wallaby).
List of Publications
Note: Opening the pdf-files requires a pdf-reader (e.g. Adobe Reader).
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.:
Self-Organization of Stem Cell Colonies and of Early Mammalian Embryos: Recent Experiments Shed New Light on the Role of Autonomy vs. External Instructions in Basic Body Plan Development.
Cells 5(4): E39 (2016). DOI: 10.3390/cells5040039
PubMed
Cells Website
pdf-download (5.16 MB)
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)
DENKER, H.-W., BETTERIDGE, K.J. , and SIROIS, J.:
Shedding of the "capsule" and proteinase activity in the horse embryo.
(Abstr.) IV Int. Sympos. on Equine Reproduction, Calgary 1986. J. Reprod. Fert. Suppl. 35, 703 (1987). DOI: 10.13140/RG.2.2.23539.96801
pdf-download (366 KB)
poster (6.09 MB)
DENKER, H.-W. and TYNDALE-BISCOE, C.H.:
Embryo implantation and proteinase activities in a marsupial (Macropus eugenii): Histochemical patterns of proteinases in various gestational stages.
Cell Tissue Res. 246, 279-291 (1986).
PubMed
SpringerLink
DENKER, H.-W.:
Embryo implantation and proteinase activities in a marsupial (Macropus eugenii): II. Preliminary characterization of proteinases.
Manuscript (1986). DOI: 10.13140/RG.2.2.21151.18089
pdf-download (12.6 MB)
TISLJAR, U. and DENKER, H.-W.:
Rabbit uterine proteinases related to implantation.
Abstract No. 148, 1th Meeting of the Europ. Soc. of Human Reproduction and Embryology, Bonn 1985. Human Reprod. 1 (Suppl. 1), 50 (1986)
pdf-download (195 KB)
TISLJAR, U. and DENKER, H.W.:
Partial purification and characterization of a trypsin-like proteinase from rabbit preimplantation uterine fluid.
Biol. Chem. Hoppe-Seyler 366, 1053-1055 (1985). PubMed pdf-download (1.65 MB)
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)
MEINSHAUSEN, E. und DENKER, H.-W.:
Entwicklungsleistungen von Kaninchenembryonen trotz Hemmung der Anheftung in utero.
Verh. Anat. Ges. 77, Anat. Anz. Suppl. 154, 421-423 (1983). pdf-download (1.16 MB)
DENKER, H.-W. and TYNDALE-BISCOE, C.H.:
Proteasen und Embryo-Implantation bei einem Beuteltier (Macropus eugenii).
(Abstr.) 3. Arbeitstagung der Anatomischen Gesellschaft, Würzburg 1982. Anat. Anz. 153, 268 (1983)
DENKER, H.-W.:
Proteases of the blastocyst and of the uterus.
In: Proteins and Steroids in Early Pregnancy (H.M. Beier and P. Karlson, eds.). Berlin: Springer-Verlag, 1982, pp. 183-208. DOI: 10.1007/978-3-642-67890-5_16
SpringerLink
pdf-download (10.1 MB)
DENKER, H.-W. and MEINSHAUSEN, E.:
Continued differentiation of mammalian embryos in utero after blockage of implantation.
Abstract No. 22, XVth EDBO International Embryological Conference, Strasbourg, 1982. DOI: 10.13140/RG.2.2.28742.91201
abstract (376 KB)
poster (11.8 MB)
DENKER, H.-W.:
The role of blastolemmase in implantation initiation in the rabbit.
In: Cellular and Molecular Aspects of Implantation (S.R.Glasser and D.W. Bullock, eds.). New York and London: Plenum Press, 1981, pp. 415-416.
SpringerLink
pdf-download (687 KB, with kind permission of Springer Science and Business Media)
DENKER, H.-W.:
Proteinases and implantation.
In: Embryonic Diapause in Mammals (A.P.F. Flint, M.B. Renfree and B.J. Weir, eds.). J. Reprod. Fert., Suppl. 29, 183-186 (1981). PubMed
DENKER, H.-W. and TYNDALE-BISCOE, C.H.:
Implantation-associated proteinase activities in a marsupial (Macropus eugenii).
(Abstr.) 14th Annual Meeting, Society for the Study of Reproduction, Corvallis, Oregon 1981. Biol. Reprod. 24, Suppl. 1, 78A (1981)
pdf-download (373 KB)
DENKER, H.-W.:
Die Anheftungsphase der Implantation: Untersuchungen zur Rolle bestimmter Proteinasen beim Kaninchen.
(Abstr.) Verh. Anat. Ges. 74, Anat. Anz. Suppl. 148, 349 (1980)
pdf-download (188 KB)
DENKER, H.-W.:
Role of proteinases in implantation.
In: Blastocyst-Endometrium Relationships (F.Leroy, C.A. Finn, A. Psychoyos and P.O. Hubinont, eds.) (Prog. Reprod. Biol., Vol. 7). Basel: S. Karger, 1980, pp. 28-42. pdf-download (39.0 MB)
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.
pdf-download (5.42 MB)
ScienceDirect
GoogleScholar
DENKER, H.-W. and FRITZ, H.:
Enzymic characterization of rabbit blastocyst proteinase with synthetic substrates of trypsin-like enzymes.
Hoppe-Seyler´s Z. Physiol. Chem. 360, 107-113 (1979). PubMed pdf-download (3.19 MB)
DENKER, H.-W.:
Inhibitors of trophoblast proteinases.
In: The Biology of the Fluids of the Female Genital Tract (F.K.Beller and G.F.B. Schumacher, eds.). New York/Amsterdam/Oxford: Elsevier/North-Holland, 1979, pp. 151-161. pdf-download (4.34 MB)
DENKER, H.-W., ENG, L.A. and HAMNER, C.E.:
Studies on the early development and implantation in the cat. II. Implantation: proteinases.
Anat. Embryol. 154, 39-54 (1978).
PubMed
SpringerLink
DENKER, H.-W.:
The role of trophoblastic factors in implantation.
In: Novel Aspects of Reproductive Physiology. Seventh Brook Lodge Workshop on Problems of Reproductive Physiology, 1977 (C.H. Spilman and J.W. Wilks, eds.). New York/London: Spectrum Publications, Inc., 1978 (distributed by Halsted Press, a division of John Wiley & Sons, New York etc.), pp. 181-212. pdf-download (67.7 MB)
DENKER, H.-W.:
The role of trophoblast-dependent and of uterine proteases in initiation of implantation.
In: Human Fertilization. International Workshop Essen, July 1976 (H. Ludwig and P.F. Tauber, eds.). Stuttgart: Georg Thieme Publishers, 1978, pp. 204-214. pdf-download (24.0 MB)
DENKER, H.-W.:
The role of certain proteinases in implantation initiation in the rabbit.
(Abstr.) XIII. International Embryological Conference, Berlin, September 1978
pdf-download (315 KB)
DENKER, H.-W., MOOTZ, U. und GERDES, H.-J.:
Ultrastrukturelle Untersuchungen der normalen und durch Proteinaseinhibitoren gehemmten Implantation beim Kaninchen.
(Abstr.) Veterinär-Humanmedizinische Tagung, Deutsche Gesellschaft zum Studium der Sterilität und Fertilität, Giessen, 1978, pp. 19-21
pdf-download (863 KB)
DENKER, H.-W.:
Implantation: The Role of Proteinases, and Blockage of Implantation by Proteinase Inhibitors.
Berlin-Heidelberg-New York: Springer-Verlag, 1977 (= Adv. Anat. Embryol. Cell Biol., Vol. 53, Fasc. 5). (English version of Habilitation Thesis). Print-ISBN: 978-3-540-08479-2. DOI: 10.1007/978-3-642-66781-7
PubMed
actual flyer
original flyer (21.1 MB)
German National Library
DENKER, H.-W., PETZOLDT, U.:
Proteinases involved in implantation initiation in the rabbit: microdisc electrophoretic studies.
Cytobiologie (European J. Cell Biology) 15, 363-371 (1977).
Scopus
pdf-download (3.37 MB)
DENKER, H.-W.:
Mechanismen der Implantation des Säugetierembryos und ihre experimentelle Beeinflussung.
Habilitationsschrift, Medizinische Fakultät an der Rheinisch-Westfälischen Technischen Hochschule, Aachen 1976. Deutsche Nationalbibliothek
DENKER, H.-W.:
Interaction of proteinase inhibitors with blastocyst proteinases involved in implantation.
In: Protides of the Biological Fluids, Proceedings of the XXIIIrd Colloquium, Brugge 1975 (H. Peeters, ed.) Oxford etc: Pergamon Press, 1976, pp. 63-68. pdf-download (2.55 MB)
DENKER, H.-W. and HAFEZ, E.S.E.:
Proteases and implantation in the rabbit: role of trophoblast vs. uterine secretion.
Cytobiologie 11, 101-109 (1975). PubMed pdf-download (3.03 MB)
DENKER, H.-W.:
Implantation des Kaninchenkeims im Uterus: Bedeutung von Enzymen des Embryos bzw. des Endometriums.
Verh. Anat. Ges. 69, Anat. Anz. Suppl. 138, 281-289 (1975). PubMed pdf-download (2.92 MB)
DENKER, H.-W.:
Trophoblastic factors involved in lysis of the blastocyst coverings and in implantation in the rabbit: observations on inversely orientated blastocysts.
J. Embryol. Exptl. Morphol. 32, 739-748 (1974).
PubMed
Development
DENKER, H.-W.:
Blastocyst enzymes and implantation in the rabbit.
(Abstr.) VIth Ann. Meet. Soc. Study of Reproduction, Athens, Georgia, 1973. Biology of Reproduction 9, 102-103 (1973)
pdf-download (327 KB)
DENKER, H.-W.:
Blastocyst protease and implantation: Effect of ovariectomy and progesterone substitution in the rabbit.
Acta endocr. (Kbh.) 70, 591-602 (1972). PubMed pdf-download (25.0 MB)
DENKER, H.-W.:
Enzym-Topochemie von Frühentwicklung und Implantation des Kaninchens. III. Proteasen.
Histochemie 25, 344-360 (1971). PubMed pdf-download (2.72 MB, with kind permission of Springer, Heidelberg)
DENKER, H.-W.:
Zur Enzym-Topochemie von Frühentwicklung und Implantation des Kaninchens.
Dissertation, Medizinische Fakultät der Philipps-Universität, Marburg/Lahn 1970. German National Library