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Approach to develop a new treatment for patients with implantationfailure using peripheral blood mononuclear cells

Research Project

Project/Area Number 09671673
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

NAKAYAMA Takahiro  Faculty of Medicine, Obstetrics and Gynecology, Kyoto University, Assistant Professor, 医学研究科, 助手 (70273448)

Co-Investigator(Kenkyū-buntansha) MAEDA Michiyuki  Institute for frontier Medical Sciences, Kyoto University, Associate Professor, 再生医科学研究所, 助教授 (20027329)
HIGUCHI Toshihiro  Faculty of Medicine, Obstetrics and Gynecology, Kyoto University, Assistant Professor, 医学研究科, 助手 (00283614)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsimplantation failure / endometrium / Peripheral blood mononuclear cell / BeWo cell / implantation / LIF / splenocyte / 着床障害 / 不妊症 / 体外受精-胚移植法 / 胚 / リンパ球 / leukemia inhibitory factor
Research Abstract

Systemic administration of splenocytes from ICR mice in the early stages of pregnancy promoted the receptivity of the uterus on pseudopregnant day 2. Splenocytes derived from pregnancy day 4 mice more effectively facilitated embryo implantation than splenocytes derived from pseudopregnancy day 4 and diestrous day 2 mice, suggesting that the presence of an embryo in the donor mice for splenocyte preparation is important for the effect of splenocytes on implantation. To investigate the effect of splenocytes on endometrial differentiation, the expression of LIFmRNA in the uterus was examined. In ovariectomized mice, administration of splenocytes from early pregnant mice induced the expression of LIFmRNA which was also observed with estradiol administration. Intra-endometrial injection of splenocytes from early pregnant mice also enhanced embryo implantation. These findings suggest that the effects of splenocytes from early pregnant mice on implantation are independent of the ovary, and di … More rectly facilitate endometrial differentiation. To estimate whether immune cells promote embryo implantation by direct action on embryos or not, we examined the effect of human peripheral blood mononuclear cells (PBMC) derived from early pregnant women on BeWo cell invasion and, outgrowth and invasion of murine blastocysts using in vitro invasion assay. PBMC promoted the invaded cell number of BeWo cells and facilitated outgrowth and invasion of murine blastocysts. Furthermore, the promoting effect of PBMC derived from non-pregnant women. These promotion effects on BeWo cells and murine blastocyst invasion could by induced by the coculture with r-hCG in PBMC derived from non-pregnant women, suggesting that the promoting effect of peripheral immune cells, which are observed in the presence of an embryo, is induced by hCG.
Based on these results, we proposed a new treatment for implantation failure in which autologous peripheral immune cells pretreated with r-hCG are injected into the endometrium to facilitate endometrial defferentiation and embryo implantation in cases of implantation failure. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Nakayama T,FujiwaraH,Yamada S,Tastumi K,et al.: "Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients"Fertil Steril. 69. 784-788 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada S,Fujiwara H,Ueda M,Honda T,Nakayama T,et al.: "A monoclonal antibody,HCL-2 raised against human luteal cells reacts with apolipoprotein-B and detects the uptake of low density lipoprotein by luteinizing granulosa cells"Hum Reprod. 13. 936-943 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada S,Fujiwara H,Kataoka N,Honda T,Nakayama T,et al.: "Stage-specific uptake of apolipoprotein-B ovarian follicles and corpora lutea of the menstrual cycle and early pregnancy"Hum Reprod. 13. 944-952 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama T,Fujiwara H,Tatsumi K,Fujita K,et al: "A new assisted hatching technique using a piezo-micromanipulator"Fertil Steril. 69. 784-788 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujita K,Nakayama T,Takabatake K,et al.: "Administration of thymocytes derived from non-pregnant mice induces endometrial receptive stage and leukemia inhibitory factor expression in the uterus"Hum Reprod. 13. 2888-2894 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama T, Fujiwara H, Yamada S, Tatsumi K, Honda T, Fujii S: "Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients."Fertil Steril. 69. 784-788 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada S, Fujiwara H, Ueda M, Honda T, Nkayama T, Higuchi T, Mori T, Maeda M: "A monoclonal antibody, HCL-2, raised against human luteal cells reacts with apolipoprotein-B and detects the uptake of low density lipoprotein by luteinizing granulosa cells."Hum Reprod. 13. 936-943 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada S, Fujiwara H, Ueda M, Honda T, Nkayama T, Higuchi T, Mori T, Maeda M: "Stage-specific uptake of apolipoprotein-B in ovarian follicles and corpora lutea of the menstrual cycle and early pregnancy."Hum Reprod. 13. 944-952 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama K, Fujiwara H, Tastumi K, Fujita K, Higuchi T, Mori T: "A new assisted hatching technique using a piezo-micromanipulator."Fertil Steril. 69. 784-788 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamada S, Fujiwara H, Ueda M, Honda T, Nkayama T, Higuchi T, Mori T, Maeda M: "Administration of thymocytes derived from non-pregnant mice induces endometrial receptive stage and leukemia inhibitory factor expression in the uterus."Hum Reprod. 13. 2888-2894 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nakayama,T: "A new assisted hatching technique using a piezo-micromanipulator." Fertility and Sterility. 69. 784-788 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujita,K: "Administraion of thymocytes derived from non-pregnant mice induces endometrial receptive stage and leukemia inhibitory factor expression in the uterus." Human Reproduction. 13. 2888-2894 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takabatake,K: "Intravenous administration of splenocytes in early pregnancy changes the implantation window in mice." Human Reproduction. 12. 583-585 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takabatake,K: "Splenocytes in early Pregnancy Promote embryo implantation by regulating endometrial differentiation in mice." Human Reproduction. 12. 2102-2107 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakayama,T: "Clinical application of a new assisted hatching method using a piezo-micromanipulator for morphologically low-quality embryos in poor-prognosis infertile patients Fertil Steril in press." Fertility and Sterility. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamada,S: "Human granulosa cell express integrin α2 and collagen Type IV : possible involvement of collagen Type IV in granulosa cell luteinization. Hum Reprod.in press." Human Reproduction. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakayama T: "A new assisted hatching technique using a piezo-micromanipulator." Fertil Steril.(in press.).

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujita K: "Tymocytes promote embryoimplantation by regulating endometrial differentiation." Hum Reprod.(in press.).

    • Related Report
      1997 Annual Research Report
  • [Publications] Takabatake K: "Intravenous administration of splenocytes in early pregnancy chanages the implantation window in mice." Hum Reprod.12. 583-585 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takabatake K: "Splenocytes in early pregnancy promote embryo implantation by regulating endometrial differentiation in mice." Hum Reprod.12. 2102-2107 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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