Department of Obstetrics and Gynecology, Institute of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Am J Pathol. 2011 Feb;178(2):506-14. doi: 10.1016/j.ajpath.2010.10.005.
Female CBA/J mice impregnated by male DBA/2J mice (CBA/J×DBA/2J matings) are prone to spontaneous abortion, although the reason for this is unclear. In this study, the stathmin-1 expression pattern was evaluated in uterine natural killer (uNK) cells purified from CBA/J×DBA/2J matings. Results were compared with those in a CBA/J×BALB/c control group that yields successful pregnancies. The mean ± SD percentage of stathmin-1(+) cells in the CD49b(+) uNK cell population was lower in CBA/J×DBA/2J mice (0.7% ± 0.4%) than in control CBA/J×BALB/c mice (4.9% ± 1.5%, P < 0.01) using flow cytometry, and the intracellular stathmin-1 level in uNK cells was lower in CBA/J×DBA/2J mice than in control mice using Western blot analysis. Co-localization of lectin from Dolichos biflorus agglutinin (DBA-lectin) and stathmin-1 was confirmed using multivision immunohistochemical analysis. The frequency of stathmin-1(+)DBA-lectin(+) cells was lower in CBA/J×DBA/2J mice than in CBA/J×BALB/c mice. A similar trend in the frequency of stathmin-1(+)CD56(+) cells was seen in patients with unexplained spontaneous abortion compared with normal early pregnancy. A neutralizing antibody against stathmin-1 further increased the percentage of embryo loss in CBA/J×DBA/2J matings. These results provide evidence that stathmin-1 expression in uNK cells at the maternal-fetal interface may help modulate uNK cell function and may be beneficial for a successful pregnancy.
CBA/J 雌鼠与 DBA/2J 雄鼠交配（CBA/J×DBA/2J 交配）易发生自发性流产，但其原因尚不清楚。在本研究中，评估了从 CBA/J×DBA/2J 交配中纯化的子宫自然杀伤（uNK）细胞中的 stathmin-1 表达模式。结果与产生成功妊娠的 CBA/J×BALB/c 对照组进行了比较。流式细胞术检测结果显示，CD49b+uNK 细胞群中 stathmin-1（+）细胞的平均百分比（±SD）在 CBA/J×DBA/2J 小鼠中较低（0.7%±0.4%），而在对照组 CBA/J×BALB/c 小鼠中较高（4.9%±1.5%，P<0.01）。Western blot 分析显示，uNK 细胞中的 stathmin-1 细胞内水平在 CBA/J×DBA/2J 小鼠中低于对照组。使用多视免疫组化分析证实了从菜豆凝集素（DBA-lectin）和 stathmin-1 的凝集素的共定位。在 CBA/J×DBA/2J 小鼠中，stathmin-1（+）DBA-lectin（+）细胞的频率低于 CBA/J×BALB/c 小鼠。在不明原因自发性流产患者中，与正常早孕相比，stathmin-1（+）CD56（+）细胞的频率也呈类似趋势。针对 stathmin-1 的中和抗体进一步增加了 CBA/J×DBA/2J 交配中胚胎丢失的百分比。这些结果提供了证据，表明母体-胎儿界面 uNK 细胞中的 stathmin-1 表达可能有助于调节 uNK 细胞的功能，并且可能有利于成功妊娠。
