The role of oxygen radical-mediated signaling pathways in endometrial function

Cells living under aerobic conditions always face an oxygen paradox. Oxygen is necessary for cells to maintain their lives. However, toxic reactive oxygen species such as the superoxide radical, the hydroxyl radical and hydrogen peroxide are generated from oxygen and damage cells. Oxidative stress occurs as a consequence of excessive production of reactive oxygen species or impaired antioxidant defense systems. Antioxidant enzymes include two types of superoxide dismutase (SOD), which specifically scavenges superoxide radicals: copper-zinc SOD, which is located in the cytosol and Mn-SOD, which is located in the mitochondria. SOD is the first enzymatic step in the defense system against oxidative stress. In addition to ovarian steroid hormones, a number of local factors such as cytokines, growth factors and eicosanoids have been reported to be involved in the regulation of endometrial function. Recently, much attention has been focused on the finding that reactive oxygen species act as second messengers in the regulation of cellular function. Since reactive oxygen species are generated, and SOD is expressed, in the endometrium, it is possible that reactive oxygen species and SOD work as local regulators of endometrial function. The present review summarizes recent findings that reactive oxygen species and SOD play important roles in the process of reproductive physiology such as decidualization and menstruation in the human endometrium.