2005 Fiscal Year Final Research Report Summary
Implantation success and establishment of pregnancy through the regulation of interferon gene
| Project/Area Number |
14206032
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied animal science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
IMAKAWA Kazuhiko The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (00291956)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Senkiti The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院・農学生命科学研究科, 教授 (80114487)
TANAKA Satoshi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (90242164)
HORI Masatoshi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院・農学生命科学研究科, 助教授 (70211547)
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| Project Period (FY) |
2002 – 2005
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| Keywords | Gene / Transcriptional regulation / Animal / Implantation / Interferon / Chemokine / Trophoblast cell / Uterine endometrium |
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| Research Abstract |
Interferon-tau (IFNτ) expression is subject to temporal and spatial limits since its production is restricted to trophoblast cells during peri-implantation period. Using a trophectoderm specific transcription factor, Cdx2,IFNτ transcription reached more than 30 fold increase. Cdx2 binding to the upstream region of IFNτ was also demonstrated. However, temporal expression of IFNτ could not be elucidated during this funding period.
Pregnancy specific gene expression was identified using cDNA subtraction studies between pregnant and cyclic uterine endometrium. These include CXC chemokines. IP-10, MIG and ITAC, all of which appeared to be expressed by macrophages located in the subepithelial region of the uterine endometrium. These chemokine especially IP-10 expressions were enhanced with the addition of IFNτ, resulting in the formation of concentration gradients within the uterus. Conceptuses were identified as having a receptor CXCR3, which recognizes IP-10's concentration gradients, and m
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igrated toward the higher concentrations, the implantation sites. During this migration, conceptuses started to express integrins, α_5,α_v and β_3. At the uterine sides, this gradient is recognized through CXCR3 located on the immune cells, particularly NK cells, which also migrate toward the implantation sites. The NK cells produce interleukin-10 (IL-10), resulting in the uterine environments suitable for pregnancy establishment. These finding were resulted from the 16-year collaboration with Dr.R.K.Christenson at USDA.
Unfortunately, the development of ES and TS cells were not successful despite of numerous experimentations. Attempts were also made to develop in vitro experimental system with primary cells from conceptuses. However, the primary cells change their characters, which made more difficult in the generation of in vitro cell culture systems that mimic in vivo implantation processes. Together, we have elucidated molecular mechanisms by which conceptus implantation to the uterine endometrium proceeds in the ruminant ungulates. Less
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