ER antagonist (ICI) partially counteracts IS resorption caused by PR antagonist (Onapristone)

ANA CECILIA MESTRE CITRINOVITZ; VERONIKA KLEFF; GRISELDA VALLEJO; ELKE WINTERHAGER; PATRICIA SARAGÜETA

Essen

Conferencia; 7th International Conference on the Female Reproductive Tract; 2013

University of Duisburg-Essen

Although decidua is critical in implantation, the hormonal regulated pathway of decidualization is still elusive. We previously described a role of progesterone (PR) and estradiol (ER) receptors in the growth and differentiation of different decidual regions; and showed that pERK1-2 regulates expression levels of ERalpha. Moreover pERK seems to be responsible for maintaining the proliferation capacity of stromal cells, while limiting the differentiation process in the region between the mesometrial and antimesometrial decidual tissues. Here we describe progesterone (PR) and estrogen receptors (ER) functions in in vivo decidualization; analyzing the morphology of 7 days post-coitum (dpc) implantation sites (IS) of rats treated during days 5 and 6 with pure progesterone, Onapristone, (ONA) or estrogen, ICI182.780 (ICI) antagonists alone and in combination. We found that ICI alone did not show evident effects on cellular differentiation and proliferation. Nevertheless, a drastic effect was observed in the blood vessel formation at the Mesometrial part of the decidua. ONA treatment completely avoided decidua development by day 7pc. The combination of ONA and ICI counteracted ONA induced resorption, increased pERK level and decreased differentiation markers Desmin ?an established structural decidual marker- and Cyclin D3 ?a poliploidization and terminal differentiation marker. To further analyze if this decidual rescue was sufficient to support placental and embryonic development allowing the birth of pups, we analyzed 7, 10, 14 and 20dpc of ONA+ICI treated rats. We observed heterogeneous results at 10dpc, showing some IS resorpted and others presented a small placenta and embryo development. At 14 dpc the IS were completely resorpted. Nevertheless, the pattern was always heterogeneous, showing different stages of the resorption process and different effects of the treatment in each rat and each implantation site. These results show that the balance between PR and ER is necessary for decidual development and support a role of p-ERK1/2 as a main player in decidual development.