(4)トロフィニンに着目した子宮内膜の機能調節とトランスレーショナルリサーチ(シンポジウム2「子宮内膜の機能調節とその病態」,第62回日本産科婦人科学会・学術講演会)

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The process of human embryo implantation is initiated by an apical adhesion between two epithelia, trophectoderm and endometrial epithelial cells. Trophinin is a membrane protein mediating apical cell adhesion between trophoblastic cells and endometrial epithelial cells through homophilic trophinin-trophinin binding. Our previous study showed that trophectoderm cells of the blastocyst of primates, likely including humans, express trophinin on their cell surface. When primary cultured human endometrial epithelial cells were treated with hCG and IL-1β, these cells expressed trophinin and adhered to trophoblastic HT-H cells. In order to analyze signal transduction triggered by trophinin-mediated cell adhesion, we screened a peptide display phage library and identified GWRQ (glycine-tryptophan-arginine-glutamine) peptide. GWRQ binds to the extracellular domain of trophinin and mimics trophinin mediated cell adhesion. GWRQ activated cultured human trophoblastic HT-H cells in vitro, promoting invasion and proliferation. By contrast, GWRQ peptide did not activate but rather induced apoptosis of human endometrial epithelial SNG-M cells cultured in vitro. Results obtained in SNG-M cells are consistent with findings that human endometrial epithelial cells adhering to the blastocyst undergo apoptosis, allowing trophoblast invasion of maternal tissue. The use of SNG-M cells will enable us to define mechanisms underlying adhesion-dependent apoptosis of human endometrial epithelial cells occurring in the process of human embryo implantation. We developed hCG-coated agarose beads, mimicking physical and physiological features of an implantation stage human blastocyst. When hCG-coated beads were applied to primary cultured human endometrial epithelial cells in the presence of IL-1β, these beads induced strong trophinin expression and morphology relevant to implantation in endometrial cells. Furthermore, hCG and IL-1β treated endometrial epithelial cells acquired the activity for apical cell adhesion with trophinin-expressing trophoblastic HT-H cells. Within a limited experiments with monkeys, we could detect a tendency to increase in pregnancy rate.
2011-01-01

(4)トロフィニンに着目した子宮内膜の機能調節とトランスレーショナルリサーチ(シンポジウム2「子宮内膜の機能調節とその病態」,第62回日本産科婦人科学会・学術講演会)

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