Ovarian steroid receptors and activated MAPK in the regional decidualization in rats

VALLEJO G; MESTRE-CITRINOVITZ AC; MOENCKEDIECK V; GRUEMMER R; WINTERHAGER E; SARAGÜETA P

BIOLOGY OF REPRODUCTION

SOC STUDY REPRODUCTION

Año: 2010

0006-3363

Though the decidua serves a critical function in implantation, the hormonal regulated pathway in decidualization is still elusive. Here we describe in detail the regional distribution and the effects of progesterone (PGR), estrogen receptors (ESR) and MAPK activation on decidualization. We showed an increase in PGR A, PGR B, ESR1, and p-MAPK 3-1 but not in ESR2, in the decidual tissue up to Day 8 of pregnancy. PGR was predominantly found in the nuclei of mesometrial decidual cells and of undifferentiated stromal cells where it colocalizes with ESR2 and ESR1. In the antimesometrial decidua, all receptors showed cytoplasmic localization. MAPK 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 decidual tissue and downregulated 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 p-MAPK3-1 level. The inhibition of MAPK3-1 phosphorylation by the inhibitor PD98059 impaired the extent of decidualization and the closure reaction of the implantation chamber, and significantly down regulated 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 of p-MAPK3-1 in regulating expression levels of ESR1, thereby keeping proliferation capacity of stromal cells and limiting the differentiation process in specified regions of decidual tissues.