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Southern Illinois University School of Medicine

Department of Physiology

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1. Effect of the Conceptus on the Endometrium During Implantation.

A proper dialogue between the conceptus and mother during the implantation process 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 while 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 during implantation: (1) there are conceptus-dependent changes in the endometrial expression of "angio-modulatory" genes, (2) there are conceptus-dependent changes in the endometrial vasculature and (3) uterine natural killer cells are mediators of conceptus-dependent vascular changes in the endometrium. 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 along with those to prevent later gestational problems.

2. Molecular Changes in Endometrial Stromal Cells Undergoing the Early Stages of Differentiation into Decidual Cells.

An amazing change which occurs in the endometrium during implantation is the process of differentiation of the endometrial fibroblast-like cells into very large polyploid decidual cells. These cells surround the implanting conceptus and play a key role in providing the appropriate environment and nutrition to the developing conceptus until the mature structure of the placenta forms. One aim of our current efforts is to examine the changes that occur in the expression of certain genes in the mouse endometrium during the early phase of implantation that are related to a specific ubiquitin E3 ligase pathway. Furthermore, we are identifying new genes whose expression in the endometrium dramatically change during the process of early decidualization and determine their function. Funding for this research is currently being sought.