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多聚肌苷酸-聚胞苷酸(poly (I:C))诱导的胚胎吸收模型中的小鼠CD200+ CK7+滋养层细胞

Murine CD200+ CK7+ trophoblasts in a poly (I:C)-induced embryo resorption model.

作者信息

Lin Yi, Zeng Yaoying, Di Jingfang, Zeng Shan

机构信息

Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.

出版信息

Reproduction. 2005 Oct;130(4):529-37. doi: 10.1530/rep.1.00575.

Abstract

Cytokeratin 7 (CK7) is currently regarded as the best marker for trophoblast cells, while CD200 (OX-2), known as 'tolerance signal', plays an important role in normal pregnancy. In this study, the status of CD200 expression was investigated in BALB/c x C57BL/6 and BALB/c x BALB/c mating combinations designed as allogeneic and syngeneic murine models of induced embryo resorption, in which the resorption rate was boosted by an i.p. injection of poly (I:C), a synthetic double-stranded RNA. The percentage of CD200+ cells in the CK7+ cell population (CD200+ CK7+ percentage) and the absolute number of these cells were determined with flow cytometry, using trophoblast cells collected at day 8.5 and day 13.5 of gestation. The potential effect of poly (I:C) on CD200 expression was also evaluated by detecting the CD200+ CK7+ percentage in trophoblast cells incubated in the presence or absence of poly (I:C), in vitro. The distribution pattern of CD200+ cells at the feto-maternal interface was evaluated by immunocytochemical examination. When 10(4) cells were analyzed at day 8.5 of gestation in each case, no significant difference was observed between the poly (I:C)-treated group and the control PBS group either in the CD200+ CK7+ percentage or in the absolute number of these cells. Similar results were observed both in BALB/c x C57BL/6 mice and in BALB/c x BALB/c mice. However, the CD200+ CK7+ percentage was significantly decreased in the poly (I:C)-treated group when evaluated at day 13.5 of gestation. Accordingly, a dramatically elevated rate of embryo resorption was observed at this time point of pregnancy after the administration of poly (I:C). In addition, the CD200+ CK7+ percentage was significantly lower in trophoblast cells incubated with poly (I:C) at a certain concentration, in vitro, while histocytochemical examination showed the CD200+ cells mainly scattered in placental tissue adjacent to the interface of the placenta and uterus. This indicates that sufficient expression of the CD200 molecule on CK7+ cells at the feto-maternal interface may be necessary for the maintenance of embryos during pregnancy in this rodent model, while poly (I:C) administration may increase embryo resorption, at least partially via direct inhibition of CD200 expression on CK7+ cells.

摘要

细胞角蛋白7(CK7)目前被认为是滋养层细胞的最佳标志物,而被称为“耐受信号”的CD200(OX-2)在正常妊娠中发挥着重要作用。在本研究中,在设计为诱导胚胎吸收的同种异体和同基因小鼠模型的BALB/c×C57BL/6和BALB/c×BALB/c交配组合中研究了CD200表达状态,其中通过腹腔注射聚肌胞苷酸(poly (I:C))(一种合成双链RNA)提高吸收速率。使用妊娠第8.5天和第13.5天收集的滋养层细胞,通过流式细胞术测定CK7+细胞群体中CD200+细胞的百分比(CD200+ CK7+百分比)以及这些细胞的绝对数量。还通过检测在有或无poly (I:C)存在的情况下体外培养的滋养层细胞中的CD200+ CK7+百分比,评估了poly (I:C)对CD200表达的潜在影响。通过免疫细胞化学检查评估母胎界面处CD200+细胞的分布模式。在每种情况下,在妊娠第8.5天分析10⁴个细胞时,poly (I:C)处理组与对照PBS组在CD200+ CK7+百分比或这些细胞的绝对数量上均未观察到显著差异。在BALB/c×C57BL/6小鼠和BALB/c×BALB/c小鼠中均观察到类似结果。然而,在妊娠第13.5天评估时,poly (I:C)处理组的CD200+ CK7+百分比显著降低。因此,在给予poly (I:C)后,在这个妊娠时间点观察到胚胎吸收速率显著升高。此外,在体外以一定浓度与poly (I:C)孵育的滋养层细胞中CD2 + CK7+百分比显著降低,而组织细胞化学检查显示CD200+细胞主要散在于胎盘与子宫界面相邻的胎盘组织中。这表明在该啮齿动物模型中,母胎界面处CK7+细胞上CD200分子的充分表达可能是维持妊娠期间胚胎所必需的,而给予poly (I:C)可能至少部分通过直接抑制CK7+细胞上CD200的表达来增加胚胎吸收。

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