CONICET | Buscador de Institutos y Recursos Humanos

Proliferation of the endometrial stromal cells followed by differentiation into decidual cells is primarily governed by progesterone and estradiol. Though the decidua serves a critical function in implantation, the hormonal regulated pathway in decidualization is still elusive. Here we describe the regional distribution and the effects of progesterone receptors (PGR), estrogen rceptors (ESR), and Erk1-2 activation on decidualization. We showed an increase in PGR A, PGR B, ESR1, and phosphorylated pErk1-2 proteins, but not in ESR2, in the decidual tissue up to Day 8 of pregnancy. PGR was predominantly fund in the nuclei of mesometrial decidual cells and of undifferentiated stromal cells where it colocalizes with ESR2 and ESR1. In the antimesometrial decidua, all the receptors showed cytoplasmic localization. Erk1-2 was activated exclusively in undifferentiated stromal cells of the junctional zone between the antimesometrial and mesometrial decidua and at the border of the antimesometrial decidua. Treatment with the progesterone antagonist onapristone and/or the estrogen antagonist faslodex reduced the extent of 8 dpc decidual tissue and downregulated the levels of PGR and ESR1. The expression level of ESR2 was affected only by the progesterone receptor antagonist, while neither the antiprogestin nor the antiestrogen significantly modified the pErk1-2 level. The inhibition of Erk1-2 phosphorylation by PD98059 impaired the extent of decidualization and the closure reaction of the implantation chamber, and significantly downregulated ESR1. These results confirm a role of both steroid receptors in the growth and differentiation of the different decidual regions and suggest a new function for pErk1-2 in regulating the expression level of ESR1, thereby maintaining the proliferation capacity of stromal cells and limiting the differentiation process in specified regions of decidual tissues.