Impaired down-regulation of E-cadherin and beta-catenin protein expression in endometrial epithelial cells in the mid-secretory endometrium of infertile patients with endometriosis.

Abstract

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. 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. 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. No significant differences in E-cadherin or beta-catenin mRNA expression in microdissected epithelial cells were observed among the different groups throughout 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. 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.