Expression Of PPARγ In The Endometrium Epithelium And Its Function

Objective: The adhesion of the developing embryo and the receptive uterine endometrium is a complicated physiological process, which is one of the most important phenomenons for implantation. Many factors, such as adhesion molecules, growth factors, cytokines and hormones are involved in the process. Peroxisome proliferators activated receptor gamma (PPARγ) is a member of the nuclear hormone receptor superfamily. PPARγpossesses a broad of range of biological functions after being activated by its ligands. For example, PPARγcan take part in the cell proliferation, cell differentiation, and the lipid metabolism and carbohydrate metabolism. As for reproductive system, PPARγhas been shown to play critical roles in the stimulation of ovulation and placenta development, et al. The functional state of uterine endometrium changes cyclically, from the proliferative stage to secretory stage (early, mid, and late), with morphological and molecular alterations. rosiglitazone is the synthetic ligand of PPARγ, and has been discovered and used in the research. In this work, the expression of PPARγin the endometrium of menstrual cycle was analyzed by immunohistochemical analysis and the expression difference of PPARγbetween the high-receptive RL95-2 cells and low-receptive HEC1-A cells, as well as the changes rosiglitazone treatment and embryonic Jar cells in RL95-2 cells was detected. The adhesion percentage was calculated via in vitro embryo adhesion system.Methods: (1) The expression of PPARγwere detected by immunohistochemical analysis in the human endometrial tissues at different phases of the menstrual cycle.(2)Cell culture of human endometrial cell lines of RL95-2 cells and HEC1-A cells, as well as human embryonic cell line of JAR cells.(2)The expression of PPARγin RL95-2 cells and HEC1-A cells, as well as the level after rosiglitazone treatment and embryonic Jar cell delivery were detected by RT-PCR and Western blot.(3)The adhesion rate of Jar cells onto the RL95-2 cell monolayer and HEC1-A cell monolayer RL95-2 cells were observed and calculated after RL95-2 cells treated with rosiglitazone (10μM, 20μM).Results:(1)PPARγwas expressed in the human endometral tissues at the mid-secretory phase and up-regulated at the late-secretory phase by immunohistochemical analysis, while there was no obvious expression of PPARγin the human endometral tissues at the proliferative phase and the early-secretory phase.(2)PPARγcould be detected either in the RL95-2 cells which represent the hyper-receptive endometrial epithelium, or in the HEC1-A cells which represent the hypo-receptive endometrial epithelium on the gene level and the protein level. The expression of PPARγin RL95-2 cells was much lower than that in HEC1-A cells. The expression of PPARγin RL95-2 cells could be increased when RL95-2 cells were stimulated by either rosiglitazone or JAR cells. (3)The adhesion rate of Rl95-2 cells and JAR cells was much higher than that of HEC1-A cells and JAR cells. When the RL95-2 cells were treated by rosiglitazone in different concentration (10μM, 20μM), the adhesion rate of Rl95-2 cells and JAR cells was decreased.Conclusion:The expression of PPARγin human endometrium change dynamically in the menstrual cycle, with the highest level in the late-secretory phase. The expression level of PPARγreverses the uterine epithelial receptivity, and up-regulated after RL95-2 cells were stimulated by either rosiglitazone or JAR cells. PPARγdecreases the adhesion potential in intro implantation model. The above results suggest that PPARγmay promote the further implantation of embryo onto the uterine endometrium.