Estudo da via de sinalização do nodal no endométrio e na fisiopatologia da endometriose

Abstract

In the present study we investigated the role of Nodal, member of the TGF-beta family, and proteins related to their mechanism of signal transduction in endometrial stromal cells stimulated or not with Estrogen (10 nM), Progesterone (1M), Estrogen (10nM) + Progesterone (1M) and Estrogen (10nM) + Progesterone (1M) + cAMP (0.5mM) for 24 hours and during the process of decidualization (Estrogen + Progesterone + cAMP) for 8 days. We also evaluated the expression of these proteins in eutopic endometrium of women with and without endometriosis. The steroid hormone stimulation increased the expression of Nodal protein and gene expression of Smad 4 and Smad 7, suggesting that transduction of Nodal is activated. The increase found in the gene expression of Smad 4 and Smad 7, even with opposing biological actions, indicates that this system possessed a feedback mechanism that regulates the actions Nodal in stromal cells under the action of steroid hormones. The gene expression of Cripto was decreased during the process of decidualization of endometrial stromal cells "in vitro", suggesting that in this case it acts as an antagonist of the actions of Activin. In eutopic endometrium of women with endometriosis we found a decrease in the gene expression of Cripto and in immunoreactivity of Smad 3. These results suggest that the imbalance observed in gene expression of Cripto may have been responsible for the lower protein expression of Smad 3 in eutopic endometrium of women with endometriosis. Together, the results suggest that the Nodal signaling pathway has subtle changes in the endometrium of women with endometriosis, which do not determine imbalance in the end of the signaling (Smad 4) but may have other functional consequences, as well as being potential pharmacological targets.