The objective of the research proposed is to identify and characterize properties of the rabbit uterine surface which are required for adhesion and fusion with the trophoblastic surface of an implanting embryo. The hypothesis to be tested is that the epithelial surface is the primary site for mediation of hormonally-regulated receptiveness of the uterus, and that apical membranes of opposed trophoblast and uterine cells will adhere via receptor-ligand interactions. Biochemical and structural approaches will be employed to identify components of uterine and trophoblast surfaces which participate in the recognition, adhesion, and fusion events at implantation.
Aims of the project include 1) to characterize adhesion interactions between rabbit uterine epithelial cell cultures and trophoblast vesicle preparations and define the effects of steroid hormones and stromal cells on the interaction, 2) to identify functional adhesion components using the trophoblast vesicle-epithelium system assay, 3) to identify plasma membrane polypeptides of receptive uterine epithelium and the trophoblast surface which demonstrate complementary ligand-receptor interaction of potential relevance to implantation, and 4) to characterize the surface components identified in aims 2 and 3 with respect to potential as markers of uterine receptivity and trophoblast differentiation using structural and immunolocalization procedures. Several markers of uterine receptivity in the rabbit have been identified and the in vitro model to be employed offers promise for determining functional adhesive or fusigenic roles for these and for identifying additional adhesive membrane components. The results obtained will add to our understanding of mechanisms underlying the development of a receptive uterus as distinguished from one refractory to implantation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD029969-02
Application #
2202347
Study Section
Special Emphasis Panel (SRC (02))
Project Start
1992-12-01
Project End
1996-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Hoffman, L H; Olson, G E; Carson, D D et al. (1998) Progesterone and implanting blastocysts regulate Muc1 expression in rabbit uterine epithelium. Endocrinology 139:266-71
Olson, G E; Winfrey, V P; Matrisian, P E et al. (1998) Blastocyst-dependent upregulation of metalloproteinase/disintegrin MDC9 expression in rabbit endometrium. Cell Tissue Res 293:489-98
Olson, G E; Winfrey, V P; Matrisian, P E et al. (1997) Specific expression of haptoglobin mRNA in implantation-stage rabbit uterine epithelium. J Endocrinol 152:69-80
Das, S K; Chakraborty, I; Wang, J et al. (1997) Expression of vascular endothelial growth factor (VEGF) and VEGF-receptor messenger ribonucleic acids in the peri-implantation rabbit uterus. Biol Reprod 56:1390-9
Hoffman, L H; Winfrey, V P; Blaeuer, G L et al. (1996) A haptoglobin-like glycoprotein is produced by implantation-stage rabbit endometrium. Biol Reprod 55:176-84