Immunohistochemical characterization of extracellular matrix components during development of deciduoma and study of the effect of ovarian hormones on the expression and synthesis of extracellular matrix molecules by decidual cells in vitro

Abstract

During pregnancy in several species of mammals, including humans and mice, endometrial fibroblasts undergo extensive morphofunctional changes acquiring an epithelial phenotype and forming a new structure in the uterus called the decidua. In mice, the decidual reaction can be artificially induced (without the embryo), resulting in the formation of the deciduoma, a model of great relevance to study the influence of the embryo upon decidualization. Endometrial decidualization, an essential event for the success of pregnancy, promotes a notable remodeling of the extracellular matrix (ECM). There are evidences, many of them coming from studies of the Laboratory of Reproductive and Extracellular Matrix Biology (LBR-MEC), that remodeling of the uterine ECM is modulated by ovarian hormones estrogen (E2) and progesterone (P4) (Grants FAPESP: 10/52543-0; Salgado et al., 2009; Salgado et al., 2011; Salgado et al., 2013). However, no consistent studies about the regulation of the endometrial ECM in the absence of the embryo are available in the literature. Furthermore, it is not clarified how the ovarian hormones act on the production of ECM components by decidual cells. Thus, the present project has two major objectives: (i) to characterize the composition and organization of the ECM during the development of the mouse deciduoma by light and electronmicroscopy combined with immunohistochemistry; (ii) to study, the effect of hormones E2 and P4 on synthesis and secretion of ECM molecules by primary culture of mouse decidual cells. Analyzes will be performed by qPCR, Western blot and immunolocalization approaches. It is expected that the results can complement those already obtained by our laboratory, bringing new information concerning the factors that are implicated in the regulation of the decidual ECM. (AU)