Fertility is a key element of reproductive health and infertility is recognized as a global public health issue by the World Health Organisation (WHO). Moreover spontaneous pregnancy loss is a surprisingly common occurrence, with approximately 15% of all clinically recognized pregnancies resulting in pregnancy failure. Two or more consecutive pregnancy losses before 20weeks of gestation is defined as recurrent spontaneous miscarriage(RSM) and it represents a relevant health issue too. The failure of implantation remains an unsolved problem in reproductive medicine and is considered as a major cause of infertility in healthy women. The causes are generally recognized, including chromosomal, anatomic, endocrinological, infectious, and auto-immunologic abnormalities. However, almost 50% of such cases remains unknown. The acquisition of receptivity by the uterine epithelium and the expression of the invasive phenotype by the trophoblast involve some of the molecular events of epithelial-mesenchymal transformation including the expression of developmentally regulated complex repertoire of cell-cell adhesion receptors , providing huge potential for both recognition and signaling specificity. The association of cadherins with catenins is essential for calcium-dependent intercellular adhesiveness and they're are also of central importance for the establishment of the epithelial phenotype and for the prevention of invasiveness . In the present study we will investigate the expression of beta-catenin E-cadherin and K-cadherin in the different phases of menstrual cycle comparing infertile patients, patients with recurrent miscarrages ,as well as healthy fertile ones. Therefore we assume that their possible altered expression may be related to a defect in embryonic receptivity and thus infertility.
Only a few, small, human studies on cadherins and ß-catenin expression in normal cycling human endometrium have been reported and considering that most of the infertility, pregnancy loss and implantation failures causes remains unknown, this study would provide an important knowledge in unexplained infertility,implantation failures,pregnancy loss and recurrent spontaneous miscarriage.
It could also provide further insight into the underlying mechanisms of endometriosis-associated infertility, because the impaired down-regulation of cadherins and ß-catenin protein expression, along with Wnt/ß-catenin signaling pathway activation during the window of implantation,have been investigated as one of the potential molecular mechanisms of infertility in patients with endometriosis(1).
Moreover it would be a valid cue for further research studies, not only in the fertility field but also in the oncologist one.
Many cellular markers have been investigated and compared between cancer cells invasion and trophoblastic implantation. For example, a cellular program used by both cancer cells (2,3) and trophoblast cells (4,5)to promote invasion is epithelial-mesenchymal transition, which results in loss of cell-to-cell contact inhibition. Associated with this program are changes in integrin expression and loss of E-cadherin, allowing loss of polarity and enhanced motility (6).
The similarities between the mechanisms involved in trophoblastic invasion and malignant cell invasion are intriguing and of potential research interest. It is well known that the extravillous trophoblast cells display a phenotype strikingly similar to cancer cells with their capacity for proliferation, migration, and establishment of a blood supply, making them a compelling model for oncologic comparison (6). In addition to the shared capacity for invading through normal tissues, both cancer cells and cells of the developing placenta create a microenvironment supportive of both immunologic privilege and angiogenesis (6). Embryo implantation is a highly regulated event, which is critical for the establishment of pregnancy. Successful embryo implantation depends on the synchronized development of both the embryo and the endometrium. Several regulatory proteins recognized to play a pivotal role in cancer cell invasion have also been considered to play an important role in implantation(7).
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