Detection of Fetal Cells in the Maternal Kidney during Gestation in the Mouse
Detection of Fetal Cells in the Maternal Kidney during Gestation in the Mouse
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DOI：
10.1620/tjem.218.107
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发表时间：
2009-06-01
影响因子：
2.2
通讯作者：
Ito, Masaharu
中科院分区：
文献类型：
--
作者：
Matsubara, Keiichi;Uchida, Naoyuki;Ito, Masaharu
据报道，胎儿细胞迁移到母体血液和器官中。由于这些胎儿嵌合细胞可能参与母体对胎儿的同种异体耐受，因此胎儿嵌合细胞可能涉及母-胎免疫学和母体自身免疫性疾病的发展。然而，胎儿微嵌合体的机制和作用仍不清楚。我们的目的是描述机制，胎儿细胞成为与母体器官在怀孕期间，使用小鼠胎儿微嵌合体模型。将非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）雌性小鼠与表达增强型绿色荧光蛋白（GFP）的转基因雄性小鼠交配，并检查妊娠母亲外周血和器官中GFP阳性细胞的存在，所述非肥胖糖尿病/严重联合免疫缺陷（NOD/SCID）雌性小鼠可用于追踪母体中胎儿细胞的行为。通过流式细胞术，我们发现在妊娠第一周，在母体外周血中检测到0.95 +/- 0.48%的单核细胞为GFP阳性，因此是胎儿来源的。在妊娠第三周，该值降至0.10 +/- 0.13%（p < 0.05）。GFP阳性细胞在肾小球外系膜区和母肾近端肾小管上皮细胞中检测到。这些GFP阳性细胞还表达血管紧张素II受体亚型2（AT 2），已知其参与调节器官发生和血管反应性。因此，表达AT 2的胎儿细胞可能参与母体肾脏血管张力的调节。这些观察结果表明，胎儿细胞可以通过激活AT 2信号传导影响母体肾功能。
It has been reported that fetal cells migrate into maternal blood and organs. Since these fetal chimeric cells could be involved in maternal allogeneic tolerance to the fetus, the fetal chimeric cells might be implicated in maternal-fetal immunology and development of maternal autoimmune diseases. However, the mechanism and role of fetal microchimerism remains unclear. We aimed to describe the mechanism by which fetal cells become associated with maternal organs during pregnancy, using a mouse fetal microchimerism model. Non-obese diabetic/severe combined immunodeficiency (NOD/SCID) female mice, which are useful for tracking the behavior of fetal cells in the maternal body, were mated with transgenic males expressing enhanced green fluorescent protein (GFP), and the presence of GFP-positive cells were examined in peripheral blood and organs of pregnant mothers. By flow cytometry, we showed that 0.95 +/- 0.48% of mononuclear cells detected in the maternal peripheral blood were GFP-positive, and thus of fetal origin, during the first gestational week. This value decreased to 0.10 +/- 0.13% during the third gestational week (p < 0.05). GFP-positive cells were detected in the extraglomerular mesangial region and among the epithelial cells of the proximal renal tubule of the maternal kidney. These GFP-positive cells also expressed angiotensin II receptor subtype 2 (AT2), which is known to participate in regulating organogenesis and vasoreactivity. Fetal cells expressing AT2 may therefore be involved in the regulation of vascular tone in the maternal kidney. These observations suggest that fetal cells could influence maternal renal function through activation of the AT2 signaling.