胚により感作された末梢血リンパ球の胚着床促進機構の解析 : ヒト着床障害患者に対する新しい免疫療法を目指して (<シンポジウム>2. 母児間免疫応答の異常)

概要

論文の詳細を見る
Implantation failure has been a focus of in vitro fertilization and embryo transfer therapy, in which embryos of good quality fail to implant in the endometrium. Abnormal endometrial differentiation is considered to cause implantation failure, and no effective therapy has been established to improve implantation when the endometrium does not respond to stimulation with sex steroid hormones. We speculated that peripheral immune cells receive some signals from pre-implanted embryos in the reproductive tract and then prepare for embryo implantation in the uterus. Based on this hypothesis, we investigated the effect of peripheral immune cells on embryo implantation in mice and humans. Systemic administration of splenocytes from ICR or BALB/c mice in the early stages of pregnancy promoted the receptivity of the uterus on pseudopregnant day 2 and day 1. Splenocytes derived from pregnancy day 4 mice more effectively facilitated embryo implantation than splenocytes derived from pseudo-pregnancy 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, which is reported to be in dispensable for implantation in mice 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 and this effect was greater in the T lymphocyte-rich preparation. These findings suggest that the effects of splenocytes from early pregnant mice on implantation are independent of the ovary, and directly facilitate endometrial differentiation. In addition, the mechanism of the promoting effect of splenocytes on embryo implantation resembles that of estradiol. To estimate whether immune cells promote embryo implantation by direct action on embryos or not, we examined the effect of human 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 early pregnant women was significantly higher than that of PBMC derived from non-pregnant women, suggesting that the function of PBMC changes according to the presence of conceptus during early pregnancy. These promoting effects on BeWo cells and murine blastocyst invasion could be 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, an important embryonal signal. 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 endometriuun to facilitate endometrial differentiation and embryo implantation in cases of implantation failure.
社団法人日本産科婦人科学会の論文
1999-08-01

胚により感作された末梢血リンパ球の胚着床促進機構の解析 : ヒト着床障害患者に対する新しい免疫療法を目指して (<シンポジウム>2. 母児間免疫応答の異常)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク