1998 Fiscal Year Final Research Report Summary
Approach to develop a new treatment for patients with implantationfailure using peripheral blood mononuclear cells
| Project/Area Number |
09671673
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAYAMA Takahiro Faculty of Medicine, Obstetrics and Gynecology, Kyoto University, Assistant Professor, 医学研究科, 助手 (70273448)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | implantation failure / endometrium / Peripheral blood mononuclear cell / BeWo cell / implantation / LIF / splenocyte |
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| 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
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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
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