Bovine endometrial metallopeptidases MMP14 and MMP2 and the metallopeptidase inhibitor TIMP2 participate in maternal preparation of pregnancy.
Early embryonic development is critically dependent on both maternal preparation and embryonic signalling of pregnancy. Matrix metallopeptidases (MMP) contribute to spatial and temporal matrix remodeling in the bovine endometrium. In this study we observed distinct changes in expression of MMP2, MMP14, and the metallopeptidase inhibitor TIMP2 between different phases of the estrous cycle indicating an endocrine regulation. An increase of TIMP2 protein abundance was ascertained in the uterine lumen during the time of embryo elongation. The expression pattern and cellular localization correlate well with the assumed effects of MMPs on release and activation of cytokines and growth factors directing cell migration, differentiation, and vascularization during this pivotal period of development. Specifically, active MMP2 in the endometrium may determine the allocation of growth factors supporting conceptus development. The presence of a day 18 conceptus in vivo and day 8 blastoysts in vitro induced endometrial TIMP2 mRNA expression. The results imply that TIMP2 is involved in very early local maternal recognition of pregnancy. Matrix metallopeptidases are likely to participate in remodeling processes preparing a receptive endometrium for a timely and precise regulation of embryo development.
Ulbrich
Susanne E
SE
Physiology Weihenstephan, Technical University Munich, Weihenstephaner Berg 3, 85354 Freising, Germany. ulbrich@wzw.tum.de
Meyer
Swanhild U
SU
Zitta
Karina
K
Hiendleder
Stefan
S
Sinowatz
Fred
F
Bauersachs
Stefan
S
Büttner
Mathias
M
Fröhlich
Thomas
T
Arnold
Georg J
GJ
Reichenbach
Horst-Dieter
HD
Wolf
Eckhard
E
Meyer
Heinrich H D
HH
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000502:physiology; D047108:Embryonic Development / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000502:physiology*; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011247:Pregnancy; D016415:Sequence Alignment; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000033:anatomy & histology / Q000502:physiology
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14