The research proposed will examine properties of the uterine epithelial plasma membrane which correlate with the hormone-regulated acquisition of the receptive condition to blastocyst adhesion and implantation. Progesterone- and estradiol-induced alterations in epithelial membrane properties (suface charge, specific lectin binding, glycocalyx structure, glycoprotein/polypeptide profile) have been defined for the rabbit uterus. Monospecific antisera against stage-specific membrane proteins will be produced and used as probes for the receptive state of the epithelium both in vivo and in an in vitro model system. Use of floating collagen gels for culture of uterine epithelial cells allows for retention of the cellular phenotype observed in vivo. The effects of steroid hormones and of endometrial stromal cells on the differentiation of epithelium and on the appearance of membrane markers of receptivity will be studied in this culture system. The functional role of membrane components in the interaction with trophoblast will be explored using cell adhesion assays on """"""""receptive"""""""" and """"""""non-receptive"""""""" epithelial cultures. This research will test the hypothesis that the uterine epithelium is the barrier to trophoblast attachment in the non-receptive uterus and that hormone-mediated changes in the epithelial plasmalemma are crucial to allowing adhesion and attachment at ovo-implantation. Clarifying the mechanisms for development of synchrony between the uterus and embryo is vital to understanding the implantation process and, as such, has relevance to fertility regulation in both humans and other animal species.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018123-06
Application #
3315101
Study Section
Reproductive Biology Study Section (REB)
Project Start
1983-09-01
Project End
1990-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
6
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203
Hoffman, L H; Wooding, F B (1993) Giant and binucleate trophoblast cells of mammals. J Exp Zool 266:559-77
Hoffman, L H; Winfrey, V P; Hoos, P C (1990) Sites of endometrial vascular leakage during implantation in the rabbit. Anat Rec 227:47-61
Anderson, T L; Olson, G E; Hoffman, L H (1986) Stage-specific alterations in the apical membrane glycoproteins of endometrial epithelial cells related to implantation in rabbits. Biol Reprod 34:701-20