Expression Of TM4SF3 In Human Endometrium During The Different Menstrual Cycle

BackgroundAfter the birth of Louise Brown in 1978, the Assisted Reproductive Techniques(ART) has made a great development in both clinical medicine and the basic science in the last decade, but the rate of the implantation is still between 25% and 30%, and the major reason is the reduced uterine receptivity which will affects the success of the ART. As we know, Successful implantation requires the appropriately timed arrival of a viable blastocyst into a receptive endometrium, and it is generally assumed that approximately two-thirds of the implantation failures are imputable to inadequate uterine receptivity or the defect in the essential embryo-endometrium dialogue, meanwhile the vitality of embryo only accounts for one-third of the implantation failures. The endometrium is remodeled throughout the menstrual cycle, and exhibits only a very short period of receptivity for embryo implantation, known as "implantation window". The endometrium becomes receptive to blastocyst implantation 6-8days after ovulation and last for almost 4 days, and during this period the endometrium transforms significantly in histological and functional. Implantation is a complex and precise physiological process, involving the modulation of endocrine, paracrine or autocrine, secretion of adhesion molecules and cytokines, regulation of embryo implantation. It has been reported that some molecules highly express during the implantation window, such as integrinαvβ3,selectin L, claudin E, immunoglobulin, platelet-inhibit-factor, IL-1, IL-6, and so on.Transmembrane 4 superfamily-3(TM4SF3) overexpression correlates with colorectal, pancreatic, hepatocellular and esophageal carcinoma, and also induce the angiogenesis to promote the metastasis of the carcinoma. Horcajadas used a microarray to investigate the gene expression profile of the endometrial receptivity in the nature cycle, and observed that the expression of TM4SF3 reduced significantly after the IUD insertion, and remained dysregulated 2 months or 1 year after IUD removal, idicating that TM4SF3 maybe impact on the endometrium receptivity.ObjectiveTo investigate the expression of TM4SF3 in human endometrium in the different groups, and analyze the probable relationship between the TM4SF3 and the endometrial receptivity.MethodDraw the endometrial of the patients who underwent IVF-ET for the tube infertility or male infertility reasons, and divided into three groups:the natural cycle, the controlled ovarian hyper-stimulation (COH) cycle and the hormone replacement treatment (HRT) cycle. Using real time quantitative PCR (real-time PCR) and Immunofluorence analysis to detect the expression of TM4SF3 in mRNA and protein levels, and analyze the probable relationship between the expression of TM4SF3 and the endometrial receptivity in the different period of the menstruation.Results1. TM4SF3 periodically expressed in the cytoplasm of the endometrial cells, especially in the luminal epithelial and the glandular epithelial; 2. In the nature cycle group, the expression of TM4SF3 is significantly higher during the implantation window phase than the proliferative phase (0.562±0.0296 vs 13.582±9.001, p< 0.005), including the levels of the mRNA and the protein; 3. In the COH cycle group, the expression of TM4SF3 is higher in the implantation window phase than the late proliferative phase and the early secretory phase, especially in the luminal epithelial and glandular epithelial, meanwhile the difference of the mRNA level is significant (0.234±0.156 vs 30.488±14.854,0.234±0.156 vs 1.506±1.427, p<0.001); 4.Camparing the expression of TM4SF3 during the implantation window phase in the different groups, the expression of TM4SF3 in COH cycle is higher than that of the natural cycle and the HRT cycle, especially in the glandular epithelium, and the expression of mRNA in COH group is much higher than the others (30.488±14.854 vs 13.582±9.001, p<0.001 30.488±14.854 vs 5.014±3.922, p<0.001).ConclusionThe expression of TM4SF3 is periodicity in the cytoplasm of the human endometrial cells, and increases during the implantation window phase, maybe it involves the establishment and modulation of the endometrium receptivity. The expression of TM4SF3 during the implantation window phase in the COH group is much higher than the nature cycle and the HRT cycle, suggesting that the levels of estrogen and progesterone during the implantation window may be affect the expression of TM4SF3.