title: ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.
abstract: 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.
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Xihua
authors.initials: X
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Shuyan
authors.initials: S
authors.lastname: Liu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.forename: Qianxing
authors.initials: Q
authors.lastname: Wang
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
authors.forename: Shufang
authors.initials: S
authors.lastname: Wang
authors.forename: Jianbing
authors.initials: J
authors.lastname: Liu
authors.forename: Shucheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiangbo
authors.initials: X
authors.lastname: Xu
authors.forename: Jiedong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008598:Menstruation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D052002:NF-kappa B p50 Subunit; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2