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

人胚胎着床和胎盘形成机制的分子生物学分析——从排斥力、趋化剂和膜结合肽酶的角度

• 批准号: 16390474
• 负责人: FUJIWARA Hiroshi
• 金额: $ 9.15万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390474/
• 关键词: Endometrium; Eph-ephrin; Embryo; Extravillous trophoblast; Membrane-bound peptidase; 細胞膜結合型peptidase

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.

为了证实排斥力诱导因子在调节人胚胎附着子宫内膜和穿透子宫内膜上皮层中的生理作用，我们检测了Eph-ephrin A分子和neuropilin-semaphorin分子在人子宫内膜和胚胎中的表达谱。结果发现Eph A1、A2、A4和ephrin A1在人子宫内膜上皮细胞上表达，而人和小鼠胚胎表达ephrin A1和Eph A1。贴壁实验表明，固定化Eph A1可降低小鼠胚胎的贴壁率，表明Eph-ephrin A系统可能调节胚胎与母体子宫内膜之间的相互作用时间，而细胞聚集实验表明，Ephrin A1信号可促进子宫内膜癌细胞系石川细胞的解离。该反应是可逆的，并诱导β-连环蛋白的酪氨酸磷酸化。这些结果表明Eph-ephrin系统可以诱导子宫内膜上皮细胞层间的细胞间解离，随后的分析表明绒毛外滋养细胞的侵袭是由趋化因子和趋化因子降解肽酶诱导的。血小板沉积在母体螺旋动脉中，通过分泌趋化物质，在螺旋动脉周围形成趋化因子梯度，在诱导绒毛外滋养细胞侵入动脉中起重要作用，表明排斥力和趋化力参与了早期胚胎着床和胎盘形成。

项目成果

Platelet-deriverd soluble factors induce human extravillous trophoblast migration and differentiation : platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries

血小板衍生的可溶性因子诱导人绒毛外滋养细胞迁移和分化：血小板可能是滋养细胞浸润母体螺旋动脉的调节剂

• 发表时间: 2005
• 期刊: BLOOD 106・12
• 作者: 由良茂夫;他;Kazuyo Kakui;Shigeo Yura;Kuo-Cherng Lin;Maki Takemura;Kazuyo Kakui;Shigeo Yura;Kuo-Cherng Lin;Maki Takemura;Makoto Kawamura;Yura S et al.;Lin KC et al.;Takemura M et al.;Kawamura M et al.;Kakui K et al.;由良 茂夫;由良茂夫;藤井 治子ほか;Fujiwara H;Yoshioka S et al.;Fujii H et al.;藤原 浩;藤原 浩;Fujiwara H.;Yoshioka S et al.;Fujii H et al.;Fujii H et al.;藤原 浩;Sato et al.
• 通讯作者: Sato et al.

Laminin and fibronection concentrations the follicular fluid correlate with granulose cell luteinization and oocyte quality

卵泡液中的层粘连蛋白和纤维连接浓度与颗粒细胞黄素化和卵母细胞质量相关

• 发表时间: 2004
• 期刊: Reproductive Medicine and Biology 3
• 作者: Toshihiro Takizawa;John M. Robinson;瀧澤 俊広;Toshihiro Takizawa;Toshihiro Takizawa;Toshihiro Takizawa;Sato et al.;Fujiwara et al.;Fujiwara et al.;藤原 浩;Sato et al.;Fujiwara et al.;Sato et al.;Honda et al.
• 通讯作者: Honda et al.

New regulatory mechanisms for human extravillous trophoblast invasion.

• DOI: 10.1111/j.1447-0578.2005.00104.x
• 发表时间: 2005-09-01
• 期刊: Reproductive medicine and biology
• 影响因子: 3.4
• 作者: Fujiwara, Hiroshi;Sato, Yukiyasu;Higuchi, Toshihiro
• 通讯作者: Higuchi, Toshihiro

Functional roles of cell surface peptidases in reproductive organs.

细胞表面肽酶在生殖器官中的功能作用。

• 发表时间: 2004
• 期刊: Reproductive Medicine and Biology 3
• 作者: Toshihiro Takizawa;John M. Robinson;瀧澤 俊広;Toshihiro Takizawa;Toshihiro Takizawa;Toshihiro Takizawa;Sato et al.;Fujiwara et al.;Fujiwara et al.;藤原 浩;Sato et al.;Fujiwara et al.;Sato et al.;Honda et al.;Fujiwara H;Fujiwara et al.;Honda et al.;Fujiwara H.
• 通讯作者: Fujiwara H.

Laminin and fibronection concentrations of the follicular fluid correlate with granulosa cell luteinization and oocyte quality

卵泡液的层粘连蛋白和纤维连接浓度与颗粒细胞黄素化和卵母细胞质量相关

• 发表时间: 2004
• 期刊: Reproductive Medicine and Biology 3
• 作者: Toshihiro Takizawa;John M. Robinson;瀧澤 俊広;Toshihiro Takizawa;Toshihiro Takizawa;Toshihiro Takizawa;Sato et al.;Fujiwara et al.;Fujiwara et al.;藤原 浩;Sato et al.;Fujiwara et al.;Sato et al.;Honda et al.;Fujiwara H;Fujiwara et al.;Honda et al.;Fujiwara H.;Fujiwara et al.;Honda et al.
• 通讯作者: Honda et al.