Impaired Down-Regulation of E-Cadherin and β-Catenin Protein Expression in Endometrial Epithelial Cells in the Mid-Secretory Endometrium of Infertile Patients with Endometriosis

Context: Only a few, small, human studies on E-cadherin and beta-catenin expression in normal cycling human endometrium have been reported. It remains unclear whether expression of these molecules might be altered in the endometrium of infertile patients with endometriosis. Objectives: The aim of the present study was to investigate E-cadherin and beta-catenin expression in the endometrium of infertile patients with endometriosis, those with uterine fibromas, and patients with unexplained infertility. Design: Expression levels of E-cadherin and beta-catenin mRNA and/or protein in the endometrium of infertile patients with endometriosis (n = 151), those with uterine fibromas (n = 41), patients with unexplained infertility (n = 9), as well as healthy fertile controls (n = 57) were measured. This study utilized laser capture microdissection, real-time RT-PCR, and immunohistochemistry. Results: No significant differences in E-cadherin or beta-catenin mRNA expression in microdissected epithelial cells were observed among the different groups through out the menstrual cycle. However, very low or no protein expression of E-cadherin, total beta-catenin, or dephosphorylated beta-catenin in luminal and glandular epithelial cells was detected in the mid-secretory endometrium of healthy fertile controls. E-cadherin, total beta-catenin, and dephosphorylated beta-catenin protein expression in the mid-secretory endometrium of infertile patients with endometriosis or unexplained infertility was significantly higher compared to that of healthy fertile controls in both luminal and glandular epithelial cells. Conclusions: These findings suggest that impaired down-regulation of E-cadherin and beta-catenin protein expression, along with Wnt/beta-catenin signaling pathway activation during the window of implantation, might be one of the potential molecular mechanisms of infertility in patients with endometriosis. (J Clin Endocrinol Metab 95: 3437-3445, 2010)