CONICET | Buscador de Institutos y Recursos Humanos

New Relationships for in vivo Endometrial Differentiation: role of PR, ER, ERK activation in the process of uterine stromal differentiation. Ana Cecilia Mestre-Citrinovitz1, Griselda Vallejo1, Veronika Kleff3, Elke Winterhager2,3 and Patricia Saragüeta1 1- Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina 2- Institut für Molekularbiologie - Universität Duisburg-Essen 3- Institut für Anatomie - Universität Duisburg-Essen Although decidua is critical in implantation, the hormonal regulated pathway of decidualization is still elusive. Previously we described a role of progesterone (PR) and estradiol (ER) receptors in the growth and differentiation of the different decidual regions; and shown that pERK1-2 regulates expression levels of ERalpha, dues maintaining the proliferation capacity of stromal cells and limiting the differentiation process in specified regions of decidual tissues. Here we describe progesterone (PR) and estrogen receptors (ER) functions in in-vivo decidualization; analyzing the changes in expression of 2 differentiation markers: Desmin and CyclinD3, and propose a new role for ERK activation. Analizing the kinetics of pregnancy we found that the maximal protein expression of Cyclin D3 and Desmin is detected at 7 and 6 dpc in pregnant decidua respectively. Desmin is found in the cytoplasm of the Antimesometrium (AM), while Cyclin D3 shows cytoplasmic and nuclear positive stain in the AM but excluding the primary decidual zone and nuclear staining in the Mesometrial (M) zone of 7dpc implantation sites. Activated ERK1-2 localization is restricted the stromal cells in contact to the embryo in untreated 7dpc implantation sites where CyclinD3 is excluded. To study the role of PR and ER during differentiation in early pregnancy, we injected pregnant rats with oil, PR (ONA) and ER (ICI) antagonists, and their combination at 5 and 6dpc or at 6 and 7dpc, and analyzed morphology and pERK, Desmin, Cyclin D3 and PCNA expression on 7dpc and 8dpc implantation sites (IS). The level of Desmin in 8dpc ONA treated IS is higher than 8dpc uteri and comparable to the level of 6dpc untreated rats. The combined action of ONA and ICI reduced Cyclin D3 content. We found that the earlier ONA treatment completely avoided 7dpc decidua development. While the combination with ICI rescued reabsorption, increased pERK level and decreased differentiation markers, Desmin and Cyclin D3, as compared with oil injected uteri. These results suggest that balance of PR and ER is crucial for decidualization and Erk activation limits the differentiation process of stromal cells during embryo periimplantation. Nothing to Disclose: ACM, GV, VK, EW, PS *Please take note of The Endocrine Society?s news embargo policy at www.endo-society.org/endo2013/media.cfm Sources of Research Support: CONICET PIP GRANT 2012