Development of molecular target therapy for human implantation failure focusing on nuclear transcription factor activity

以核转录因子活性为重点的人类植入失败分子靶向治疗的发展

• 批准号: 17591734
• 负责人: KIMURA Tadashi
• 金额: $ 2.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591734/
• 关键词: implantation failure; endometrium; transient in vivo gene transfer; stat-3; decoy; progesterone; decidualization; IVF-ET; stat-3; 体外受精-胚移植; 着床; Stat-3; HVJ-E; 原因不明妊娠

Using transient in vivo gene transfer system into mouse uterus, we have successfully introduced stat-3 decoy double strand oligonucleotides or dominant negative stat-3 mutant cDNA into mouse pregnant uterine cavity on day 1.5 post coitum. This procedure with Haemagglutinating Visur of Japan (HVJ)-envelope vector did not disturb the physiological course of pregnancy. After disturbing stat-3 activation at the implantation window, we noticed implantation process was totally disturbed. Evans blue injection did not induce "blue bands" at the implantation sites. Hormonal milieu including progesterone was did not altered by this treatment. Moreover, disturbing stat-3 activity also inhibit decidualization after pseudo-pregnant and mechanical stimuli in the mouse uterus.Depending on these observations, we observed stat-3 activating status in human mid-lueal endometrium obtained by endometrial dating biopsy. Immunohistochemical staining using anti phosphor-stat-3 antibody indicated that, in endometrium from infertile patients underwent 2 or more cycles of morphologically healthy embryo transfer and fail to conceive, immunoreactivity of phosphor-stat-3 tended to be weak or undetectable. Further investigation should be required to clarify the relationship between stat-3 activation status and human implantation failure. Our data may provide the clue to understand the pathophysiology of implantation failure.

利用小鼠子宫内瞬时体内基因转移系统，成功地将stat-3诱饵双链寡核苷酸或显性失活stat-3突变体cDNA导入小鼠妊娠后1.5天的子宫内。该程序与日本血凝Visur（HVJ）包膜载体没有干扰怀孕的生理过程。在植入窗口干扰stat-3激活后，我们注意到植入过程完全被干扰。伊文思蓝注射在植入部位没有诱导“蓝带”。激素环境，包括孕酮没有改变这种治疗。此外，干扰stat-3活性也抑制小鼠子宫在假孕和机械刺激后的蜕膜化。基于这些观察，我们观察了stat-3激活状态的人子宫内膜的子宫内膜年龄活检获得。免疫组化染色显示，在接受2个或2个以上周期形态健康胚胎移植且未受孕的不孕患者的子宫内膜中，phosphor-stat-3的免疫反应性较弱或检测不到。需要进一步研究以阐明stat-3激活状态与人体植入失败之间的关系。我们的数据可能提供线索，以了解种植失败的病理生理。

项目成果

Occurrence of fetal choroid plexus cysts in siblings : concerns regarding recurrence and chromosomal abnormality

兄弟姐妹中出现胎儿脉络丛囊肿：担心复发和染色体异常

• 发表时间: 2005
• 期刊: J Obstet Gynaecol Res 312
• 作者: Koyama;S.;Kimura;T.;Tokugawa;Y.;Koyama;M.;et al.
• 通讯作者: et al.

Simple and highly efficient method for transient in vivo gene transfer to mid-late pregnant mouse uterus.

简单高效的体内基因瞬时转移至中晚期妊娠小鼠子宫的方法。

• 发表时间: 2006
• 期刊: J Reprod Immunol 70(1-2)
• 作者: Koyama;S.;T.Kimura;K.Ogita;H.Nakamura;C.Tabata;K.Md Abu Hadi Noor Ali;K.Temma-Asano;K.Shimoya;T.Tsutsui;M.Koyama;Y.Kaneda;Y.Murata
• 通讯作者: Y.Murata

Elevated expression of N-acetylglucosaminyltransferase V in first trimester human placenta.

• DOI: 10.1016/j.bbrc.2005.02.186
• 发表时间: 2005-05
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Mari Tomiie;Shigeyuki Isaka;E. Miyoshi;N. Taniguchi;T. Kimura;K. Ogita;T. Tsutsui;K. Shimoya;T. Nakagawa;A. Kondo;M. Koyama;Y. Murata

Immunization of male mice with plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppress fertility in vivo

使用编码促性腺激素释放激素 (GnRH-I) 和 T 辅助表位的质粒 DNA 疫苗对雄性小鼠进行免疫抑制体内生育力

• 发表时间: 2007
• 期刊: Vaccine 25
• 作者: Khan AH;Ogita K;Tsutsui T;Kimura T;et al.
• 通讯作者: et al.

Transient local overexpression of human vascular endothelial growth factor(VEGF) in mouse feto-maternal interface during mid-term pregnancy lowers systemic maternal blood pressure

妊娠中期小鼠胎母界面短暂局部过度表达人血管内皮生长因子（VEGF）可降低母体血压

• 发表时间: 2006
• 期刊: Hormone and Metabolic Research 36
• 作者: Koyama;S.;Kimura;T^*.;Ogita;K.;et al.
• 通讯作者: et al.