Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, China.
J Cell Biochem. 2011 Mar;112(3):773-81. doi: 10.1002/jcb.22893.
The CBA/J × DBA/2 mouse mating combination is prone to spontaneous embryo loss, in contrast to the MHC-identical CBA/J × BALB/c mating combination, which yields successful pregnancies. The underlying mechanisms for these observations are unclear. In this study, multi-vision immunohistochemical staining (IHC), flow cytometry and Western blot analysis were used to detect peroxiredoxin-2 (PRX-2) expression in the uterine natural killer (uNK) cells from CBA/J × DBA/2 and CBA/J × BALB/c mice. In IHC analysis, co-localization of PRX-2 and lectin from Dolichos biflorus agglutinin (DBA-lectin) was confirmed and the frequency of PRX-2(+) DBA-lectin(+) cells was significantly lower in CBA/J × DBA/2 than CBA/J × BALB/c. In flow cytometry and Western blotting, PRX-2 was found expressed at a significantly lower level in CBA/J × DBA/2 mice. PRX-2 inhibition with a neutralizing antibody significantly decreased PRX-2 expression, increased the cytotoxicity of uNK cells, and increased the percentage of embryo loss in CBA/J × DBA/2J mice. Our data suggest that PRX-2 may be involved in the modulation of maternal-fetal tolerance and that insufficient expression of this protein may correlate with increased embryo loss in CBA/J × DBA/2J mice.
CBA/J × DBA/2 小鼠交配组合容易自发发生胚胎丢失,而 MHC 相同的 CBA/J × BALB/c 交配组合则能成功妊娠。这些观察结果的潜在机制尚不清楚。在这项研究中,使用多视野免疫组织化学染色(IHC)、流式细胞术和 Western blot 分析检测 CBA/J × DBA/2 和 CBA/J × BALB/c 小鼠子宫自然杀伤(uNK)细胞中的过氧化物酶-2(PRX-2)表达。在 IHC 分析中,确认了 PRX-2 与双花扁豆凝集素(DBA-lectin)的共定位,并且 CBA/J × DBA/2 中的 PRX-2(+) DBA-lectin(+)细胞频率明显低于 CBA/J × BALB/c。在流式细胞术和 Western blot 中,发现 CBA/J × DBA/2 小鼠中 PRX-2 的表达水平明显降低。用中和抗体抑制 PRX-2 显著降低了 PRX-2 的表达,增加了 uNK 细胞的细胞毒性,并增加了 CBA/J × DBA/2J 小鼠胚胎丢失的百分比。我们的数据表明,PRX-2 可能参与调节母胎耐受,并且这种蛋白的表达不足可能与 CBA/J × DBA/2J 小鼠胚胎丢失增加有关。