Grant: Operating Grant

Successful establishment of gestation in humans and other mammals requires complex interactions between the embryo and the uterus. An important change in the uterine lining or endometrium is the differention of a cell population to become the decidual tissue. Functional placentation requires that this differentiation occur, and its absence correlates with gestational pathology and embryo mortality. We have new evidence demonstrating that an intercellular signaling molecule in the nuclear receptor family known as liver receptor homolog-1 (Lrh-1) is essential for successful decidualization of the endometrium. We propose to further investigate this phenomenon using endometrium specific ablation of the gene in question in a transgenic mouse model and by exploring Lrh-1 signaling in human endometrial cells in vitro. We will analyze global gene expression patterns in both whole animal and cell models and explore the effects of Lrh-1 ligands in inducing endometrial differentiation. We will further investigate the molecular methods of transcriptional regulation of marker genes for decidualization. These studies are expected to provide new insight into important problems of human gestational health.