Analysis of the glycodelin-regulated cell motility and cell adhesionin human endometrial epithelial cells during implantation

人类植入的分子机制的主要部分仍然不清楚。人子宫内膜在生殖月经周期中不断重复破裂、增殖和分化，为妊娠做准备。我们已经报道了组蛋白去乙酰化酶抑制剂（HDACI）可以在没有卵巢类固醇激素的帮助下分化人子宫内膜上皮细胞和间质细胞。为了探索治疗育龄妇女的新策略，我们分析了HDACI在着床过程中是否不仅影响子宫内膜上皮细胞的分化，而且影响其增殖、运动和粘附。我们使用人子宫内膜上皮细胞的体外模型证明了以下现象（石川细胞）和胚胎细胞（石川细胞）。细胞周期阻滞在G1/S检查点或诱导细胞凋亡可下调石川细胞增殖.石川细胞运动性在单个和集体细胞迁移实验中均上调.石川细胞与胶质球的粘附能力明显增强。以HDACI剂量依赖性方式显示。总之，由卵巢类固醇激素或HDACI诱导的glycodelin可以通过对分化、增殖、运动性和粘附的积极作用来帮助着床率。提示HDACI有可能替代激素类药物，作为辅助生育的药物。

Major part of molecular mechanism(s) of human implantation still remains unclear. Human uterine endometrium repeats breakdown, proliferation and differentiation for preparation of pregnancy in reproductive menstrual cycle. We have reported that histone deacetylase inhibitors (HDACI)can differentiate human endometrial epithelial and stromal cells without assistance by ovarian steroid hormones. To develop new strategy of treatment for fertile women, we analyzed whether HDACI can affect not only differentiation but also proliferation, motility and adhesion of endometrial epithelial cells during implantation.In this study, we demonstrated the following phenomenon using in vitro model by model of human endometrial epithelial cells (Ishikawa cells) and embryonal cells (JAR cells).By treatment of ovarian steroid hormones (17beta-estradol + progesterone) or HDACI1. Ishikawa cell proliferation was down-regulated by cell-cycle arrest at G1/S check point or induced cell apoptosis.2. Ishikawa cell motility was up-regulated in both single and collective cell migration assay.3. Adhesion between Ishikawa cells and JAR spheroids were significantly enhanced.Moreover, these results were4. showed in a HDACI-dose dependent manner.5. required for glycodelin induction.Taken together, glycodelin induced by ovarian steroid hormones or HDACI can help for implantation rate through positive effect to differentiation, proliferation, motility, and adhesion. It is suggested that HDACI have a potential as a implantation-assisted reagent instead of hormonal reagents for fertile women.