Analysis of tissue remodeling mechanisms by circulating blood cells during human reproduction

人类生殖过程中循环血细胞的组织重塑机制分析

• 批准号: 20390434
• 负责人: FUJIWARA Hiroshi
• 金额: $ 12.23万
• 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: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390434/
• 关键词: 組織再構築; 黄体形成; 胎盤形成; 胚着床; 妊娠; 末梢血単核球; 血小板; 子宮内膜; 絨毛外栄養膜細胞

Although it has been widely accepted that adequate endometrial differentiation for embryo implantation is induced by ovarian sex steroid hormones, the precise molecular mechanism(s) concerning human embryo attachment to endometrial epithelium remains unclear. Accordingly, implantation failure in patients treated with in vitro fertilization and embryo transfer has been increasingly focused on in the field of assisted reproductive technology. On the other hand, during the past several decades the mechanisms for establishing maternal immune tolerance against embryo have been investigated in reproductive immunology. Recently, accumulating evidence suggests that activated immune cells actively contribute to establishment of pregnancy. In accordance with it, we found that peripheral blood immune cells positively affect function and differentiation of maternal endometrium and corpus luteum of pregnancy to facilitate embryo implantation during early pregnancy. In addition, platelets were shown to regulate vascular remodeling process in corpus luteum and placental formation. Based on these findings, we have successfully developed a new therapy for patients with implantation failure using autologous peripheral blood immune cells.

尽管卵巢性类固醇激素诱导子宫内膜分化以利于胚胎着床已被广泛接受，但关于人胚胎附着于子宫内膜上皮的确切分子机制仍不清楚。因此，在辅助生殖技术领域，接受体外受精和胚胎移植治疗的患者的植入失败越来越受到关注。另一方面，在过去的几十年中，建立母体对胚胎的免疫耐受的机制已在生殖免疫学中进行了研究。最近，越来越多的证据表明，激活的免疫细胞积极促进怀孕的建立。与此相一致，我们发现外周血免疫细胞积极影响母体子宫内膜和妊娠黄体的功能和分化，以促进早期妊娠的胚胎着床。此外，血小板被证明可以调节黄体和胎盘形成中的血管重塑过程。基于这些发现，我们已经成功地开发了一种新的治疗植入失败的患者使用自体外周血免疫细胞。

项目成果

周産期免疫、常態と病態、着床誘導機構について日本産婦人科・新生児血液学会

围产期免疫、正常和病理状况以及着床诱导机制 日本妇产科和新生儿血液学会

• 发表时间: 2008
• 作者: Harabuchi Y;Takahara M;Kishibe K;Moriai S;Nagato T;Ishii H.;黒野祐一;藤原浩
• 通讯作者: 藤原浩

着床をめぐる最近の話題、末梢血免疫細胞による胚着床誘導機構とその臨床応用

着床近期话题：外周血免疫细胞诱导胚胎着床的机制及其临床应用

• 发表时间: 2009
• 作者: 黒野祐一;田中紀充;福岩達哉;宮下圭一;早水佳子;藤原浩
• 通讯作者: 藤原浩

Histidine 379 of Human Laeverin/Aminopeptidase Q, a Nonconserved Residue within the Exopeptidase Motif, Defines Its Distinctive Enzymatic Properties

• DOI: 10.1074/jbc.m109.066712
• 发表时间: 2009-12-11
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Maruyama, Masato;Arisaka, Naomi;Tsujimoto, Masafumi
• 通讯作者: Tsujimoto, Masafumi

絨毛外栄養膜細胞特異的蛋白

绒毛外滋养层细胞特异性蛋白

• 发表时间: 2009

Circulating blood cell contribution to embryo implantation

循环血细胞对胚胎植入的贡献

• 发表时间: 2009
• 作者: 福岩達也;黒野祐一;藤原浩
• 通讯作者: 藤原浩