Exploring the expression of L-selectin ligands in human endometrium throughout the menstrual cycle

• Main Authors: Tsung-Hsuan Lai, 賴宗炫
• Other Authors: Qing-Dong Ling
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/6hu3gh

博士 === 國立中央大學 === 系統生物與生物資訊研究所 === 106 === In humans, embryo implantation is mediated by a variety of factors which are produced by both endometrium and blastocyst. Successful implantation requires a finely tuned synchrony between the embryo and receptive endometrium. However, fundamental questions about implantation remain unresolved. Initial step of embryo implantation is cell adhesion of trophectoderm of blastocyst and endometrial luminal epithelial cells of uterus, at their respective apical cell surfaces. Evidence suggests that the cell adhesion molecules play a unique role in human embryo implantation. The cell adhesion molecule family is composed of four members known as integrins, cadherins, selectins and immunoglobulins. These surface ligands, usually glycoproteins, mediate cell-to-cell adhesion. Their classical functions include maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations and tumor metastasis. Recently, researchers have given attention to the role of L-selectin ligands (LSLs) in endometrial receptivity. The related works on the expression of LSLs in human endometrium in recent years have addressed the important role of LSLs in endometrial receptivity and successful implantation. LSLs may serve as a biomarker of endometrial receptivity and may help elucidate the implantation process. However, to date, little is known about the types of LSLs in human endometrium. Furthermore, the expressions of the genes involved in the synthesis of LSLs are yet available in human being. In this study, we intend to identify the LSL genes in human endometrium and to study the expression patterns of LSLs in the fertile patients compared with the patients with adenomyosis. We recruited 41 endometrial samples from reproductive-aged women with leiomyoma, 42 endometrial samples from patients with adenomyosis, and 11 endometrial samples from menopausal women. Immunohistochemistry, western blotting, and RT-PCR were performed to evaluate LSL expression. A non-parametric Kruskal-Wallis one-way analysis of variance with multiple comparisons was performed to examine differences among menstrual phases. Immunohistochemistry analysis with MECA-79 Ab revealed strong LSL expression from the early through the mid-secretory phase in natural cycle and low expression in menopausal endometrium. Five LSL genes were found in reproductive, adenomyotic and menopausal endometrium by RT-PCR: PODXL, EMCN, CD300LG, GLYCAM1, and CD34. EMCN differed significantly between the proliferative and early-secretory phases in natural cycle (P<0.05). The significant expression of EMCN between the proliferative and early-secretory phases might play a vital role in endometrial receptivity in natural cycle. In adenomyosis, Immunohistochemistry showed that LSL is expressed with weak intensity in the endometrium in all phases. In the luminal epithelium, LSL expression increased from the proliferative to the late-secretory phase but decreased in the mid-secretory phase (the period of implantation). There were significant differences in the mean histological scores (HSCOREs) among the proliferative, early-secretory, and late-secretory phases (P<0.05). The expression patterns of five LSL genes occurred differentially among phases. Moreover, PODXL differed significantly among phases (P<0.05). The results showed that adenomyosis may cause abnormalities in LSL production in the nid-secretory phase, which may contribute to impaired endometrial receptivity and implantation failure. Further studies in vitro and in vivo are required to determine the mechanisms related to the LSL system in human endometrium and to determine its role in endometrial receptivity.