The role and distribution of Wnt/ß-catenin pathway in unexplained infertility patients

To date, the members of Wnt family, which are 19 different types, play a role during cell polarity, proliferation, apoptosis and cell migration during control of both embryonic and pathologic conditions. Signaling of Wnt is control with two different pathways. The first one that the activation of Dishevelled (Dvl) via occurring of Wnt/Fzd complex after triggering of Frizzled (Fzd) cell surface receptor is activate the actin, which provide the connection of ß-catenin to complex after fosforilation of glycogen synthase kinase-3ß (GSK-3ß). After that, the ß-katenin trigger to nucleus and transcription starts. The second one that, it is ß-catenin independent pathway and activate profillin, Rac and Rho and then cytoplasmic pathways for cell differentiation is controlled. Because of the role of the Wnt signaling pathways during epithelial-mesenchimal cell interaction without triggering of cell transcription, it was evaluated during both implantation and endometriyal cycles.Success of the implantation depends on blastocytes which processed for implantation and receptive uterus. Secretion of growth factors from both embryo and endometriyum play a role during implantation. In infertility, as well as problems of ovarian and/or sperm, in some cases, fertilization complete, but, implantation can not be occur. In this situation called unexplained infertility. While Wnt/ ß-catenin signaling pathway was observed in proliferation and early secretion phases of normal endometriyal cycle in previous studies, there was still no information about expressing of them in unexplained infertile patients endometriyum. In this study, the role and distribution of Wnt/ ß-catenin signaling pathway were aimed in proliferation and early secretion phases of endometriyal samples from unexplained infertile patients.The proliferation and secretion phase samples from control and infertile patients were done routine paraffin embedding protocol after fixing in 10% formalin solution. The sections were stained with hematoxylene-eosine for histochemical analyses, distribution of Wnt7a, ß-catenin, Fzd6 and Dkk1 was examined using indirect immunohistochemistry and in situ hibridization tecniques.After histochemical analyses, epithelium both luminal and glandular was observed histological features in both proliferative and early secretory phases.After Immunohistochemical analysis, the distribution of Wnt7a in the luminal epthelium during proliferation phase was more detectable control groups then infertile patients, however, despite the negativity in the control group in the secretion phase, the expression was observed in luminal epithelium during the secretuar phase of infertile patients. The immunoreactivity of ß-catenin in both the proliferative and secretory phases in both control and infertile groups was negative in the luminal and glandular epithelium with the stroma. In proliferative phase, the immunoreactivity of Fzd6 was detectable in stroma in both control and infertile groups, the immunoreactivity was found to be similar in both groups. İmmunoreactivity of Dkk1, in both groups and all three regions was similar during both proliferation and secretion phase and the intensity of immunoreactivity was moderate.After in situ hybridization analysis, the expression of Wnt7a was different in the luminal and glandular epithelium of both groups during in the proliferation phase, while it was similar in stroma. In secretory phase the expression of Wnt7a was higher in the luminal epithelium in infertile groups, the expression in glandular epithelium was similar with control groups. ß-catenin expressions was different in luminal and glandular epithelium from both groups in proliferative phase, the expression was negative in stroma. In secrotory phase, ß-catenin expression in the luminal and glandular epithelium was higher in infertile group than the control group, while ß-catenin expression in stroma was similar with the control group. The expression of Fzd6 was similar in both proliferation and secretory phase in both groups. Dkk1 expression was similar in both groups and in both phases.As a result, Wnt7a was secreted during proliferation phase and prepared to endometriyum for implantation, but, in infertile patients the increased of secretion of Wnt7a than control group, epithelial expression of Wnt7a was need for maternal receptivity for embryo. ß-catenin expression is observed no difference between control and infertile groups, showed that it was not changed in infertile group. The expression of Fzd6 was similar in both groups, mainly in stroma, it was required for invasion of embryo which completed adhesion. Therefore, because of decreased expression of both the epithelial Wnt7a and stromal Fzd6 in infertile patients, the implantation may be failed. In addition, the infertile groups, during both the proliferative and secretory phase, the expression of Dkk1 was negative, depending on decreased Wnt7a suggests that the secretion was inhibited.