Wu Bin, Chen Xihua, He Bin, Liu Shuyan, Li Yunfeng, Wang Qianxing, Gao Haijun, Wang Shufang, Liu Jianbing, Zhang Shucheng, Xu Xiangbo, Wang Jiedong
Reproductive Physiology Laboratory (B.W., X.C., B.H., S.W., J.L., S.Z., X.X., J.W.), National Research Institute for Family Planning, Beijing 100081, People's Republic of China; Graduate School (B.W., S.W., J.L., J.W.), Peking Union Medical College, Beijing 100730, People's Republic of China; School of Pre-clinical Sciences (S.L.), Guangxi Medical University, Nanning 530021, People's Republic of China; Basic Medical College (Y.L.), Hebei University of Traditional Chinese Medicine, Shijiazhuang 050091, People's Republic of China; Department of Cell Biology and Genetics (Q.W.), Zunyi Medical College, 563003 Zunyi, People's Republic of China; and Department of Obstetrics and Gynecology (H.G.), Baylor College of Medicine, Houston, Texas 77030.
Endocrinology. 2014 Sep;155(9):3638-48. doi: 10.1210/en.2014-1029. Epub 2014 Jun 13.
Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.
孕酮撤退会引发月经期间子宫内膜的崩解和脱落。月经是由炎症反应引起的；然而，活性氧（ROS）在月经中的作用仍不清楚。在本研究中，我们探讨了ROS在子宫内膜崩解和脱落中的作用。我们发现在小鼠类月经模型中，子宫内膜崩解前ROS水平显著升高。阴道涂片检查、子宫角形态学和子宫内膜组织学检查表明，多种ROS清除剂在该模型中显著抑制了子宫内膜崩解。此外，蛋白质印迹法和免疫组织化学分析表明，p50和p65从细胞质向细胞核的细胞内转位被ROS清除剂阻断，实时定量聚合酶链反应显示ROS清除剂降低了环氧合酶-2（COX-2）mRNA的表达。体外培养的人基质细胞也出现了类似变化。此外，蛋白质印迹法和实时定量聚合酶链反应表明，一种ROS，即过氧化氢（H2O2），在孕酮维持的情况下促进了p50和p65从细胞质向细胞核的转位，并增加了COX-2 mRNA的表达。核因子κB抑制剂MG132减少了体外培养的人基质细胞中这些变化的发生。总体来看，我们的结果提供了证据，表明某些ROS在小鼠类月经模型中对子宫内膜崩解和脱落很重要，并且至少部分通过核因子-κB/COX-2信号通路发挥作用。在人基质细胞中观察到的类似变化也可能意味着ROS是人类月经的重要介质。
