A proper dialogue between the conceptus and mother is critical for the successful establishment of normal pregnancy. Our long-range goal is to identify and determine the function of genes whose expression in the endometrium is controlled by the conceptus after the onset of implantation as the endometrium undergoes decidualization. The proposed hypothesis is that there are conceptus-dependent changes in the endometrium during the days after the onset of implantation. These changes include gene expression, angiogenesis/vascular remodeling and immune cell numbers. Specific aims are to determine in the mouse that: (1) there are conceptus-dependent changes in the endometrial expression of "angio-modulatory" genes during implantation, (2) there are conceptus-dependent changes in the endometrial vasculature during implantation and (3) uterine natural killer cells are mediators of conceptus-dependant vascular changes in the endometrium during implantation. Several in vivo approaches will be used including using normal and "knockout" mice and mice undergoing artificially-induced decidualization. In vitro approaches will involve the use of trophoblast stem cell, giant cell and endometrial stromal cell cultures. Basic research to better understand how the conceptus influences the changes that occur in the endometrium just after the onset of implantation may provide insights that can be used to develop: treatments for infertility, methods to prevent later gestational problems, or new and improved contraceptive methods.