Molecular biological analysis of mechanisms for human embryo implantation and placentation-from the perspectrives of repulsive force, chemoattractants and membrane-bound peptidases

点击翻译按钮获取中文摘要

To confirm the physiological roles of repulsive force-inducing factors in the regulation of human embryo attachment to endometrium and penetration through endometrial epithelial layer, we examined the expression profiles of Eph-ephrin A molecules and neuropilin-semaphorin molecules in the human endometrium and embryo. As a result, we found Eph A1, A2, A4 and ephrin A1 were expressed on human endometrial epithelial cells, while human and murine embryo expressed ephrin A1 and Eph A1. Attachment assay revealed that immobilized Eph A1 reduced murine embryo attachment, showing the possibility that Eph-ephrin A system regulates the timing of cross-talk period between maternal endometrium and embryo before attachment to endometrium.On the other hand, by cell aggregation assay, ephrin A1 signal promoted cell-dissociation among endometrial carcinoma-derived cell line, Ishikawa cells. This reaction was reversible and induced tyrosine phosphorylation of β-catenin. These findings suggest that Eph-ephrin system can induce intercellular dissociation among the endometrial epithelial cell layer.The subsequent analysis showed that extravillous trophoblast invasion was induced by chemokines and chemokine-degrading peptidases. It was also indicated that platelets that were deposited in the maternal spiral arteries play an important role in inducing extravillous trophoblast invasion into the artery by secreting chemoattractive substances, creating chemokine gradient around spiral artery.These findings showed that repulsive and chemoattractive forces are involved in early embryo implantation and placentation.