UNIVERSITY OF ILLINOIS
This award was issued as a 2 year extension of previous NIH grant 1R01 HD044713-01A2.
Project Title: Cell differentiation during decidualization. / Differences in cytoskeletal organization and properties of stromal cells in endometriosis.
Decidualization, which involves differentiation of stromal fibroblasts into decidual cells, is a major change that occurs in the primate endometrium after conception. Decidualization is critical for the establishment and maintenance of pregnancy. Based on our previous in vitro and in vivo results, we have proposed cytokine interleukin-1beta as one of the possible mediators of the decidualization process. We demonstrated that in vitro decidualization induced by the embryonic stimulus IL-1beta or the widely established exogenous stimulus cAMP (both in the presence of steroid hormones) is accompanied by extensive changes in the cytoskeletal architecture. Our data provide evidence that cytoskeletal dynamics (actin-myosin interactions), rather than the absolute level of cytoskeletal stiffness or the precise organization of the cytoskeleton, are the more important elements of decidualization. Despite extensive research, the etiology and pathophysiology of endometriosis and its relationship to decreased fecundity still remain unclear. Defects in the decidualization process were described in endometriosis and infertility patients. We hypothesize that the ability of stromal cells to re-organize the cytoskeleton, a process that leads to decidualization, is compromised in patients with endometriosis. The studies in the project are devoted to the differences in response to embryonic stimulus during decidualization between normal healthy stromal cells and endometriotic stromal cells (isolated from patients with endometriosis and from a baboon model of induced endometriosis).
The output of the studies would be novel knowledge gained about molecular defects during endometriosis, measurable in scientific meeting presentations and published scientific literature.