The role of Superoxid Dismutase in Endometrial Functional Integrity

Abstract

Free radicals and other reactive oxygen species (ROS) are continuously generated as byproducts of normal cellular metabolism. Cells face up against ROS using a primary antioxidant system, characterized by a group of enzymes working together and sequentially, to reduce or eliminate ROS. The three major classes of antioxidant enzymes are the superoxide dismutase, catalase, and glutathione peroxidase. Superoxide dismutase (SOD) refers to a family of enzymes that catalyze the dismutation of superoxide to hydrogen peroxide and molecular oxygen. Superoxide and SOD are necessary to maintain biological homeostasis through various functions involving several cellular signal transduction pathways. Since the discovery of SOD more than four decades ago, there have been extensive studies on their biological activities in health and disease. The unbalanced activity of those enzymes (including SOD) plays a role in the pathogenesis of many diseases such as cancer, neurodegenerative diseases, allergy, ischemia/reperfusion injury or atherosclerosis. The endometrium is a very peculiar organ that in intact, mature females responds to the effects of cyclic alternance of sex steroids (estrogens and progesterone) to accomplish complex functions, including sperm tolerance, fertilization, embryo implantation and subsequent formation of the placenta. Cyclic changes in both ROS production and SOD activity have been reported to occur in the endometrium of different species. Moreover, it has been proposed that disturbances in ROS equilibrium might induce damages to tissues and predispose to infertility and many uterine diseases. Cyclical variations in the expression of superoxide dismutase (SOD) have been reported in the human and bitch endometria. Increased SOD activity has been related to proliferation in the follicular stage of the menstrual cycle and increased levels of estrogen. In contrast, SOD activity decreases in the late secretory phase. SOD activity has been related to angiogenesis during endometrial growth, regeneration, shedding or in implantation, due to its interplay with the local cytokine network. Also, SOD downregulation may trigger apoptosis, resulting from the accumulation of ROS in tissues. Furthermore, in the uterus, a decrease in SOD activity has been connected to prostaglandin F2-alpha synthesis and the endometrial secretion at progesterone withdrawal and luteolysis in species with short lifespan corpus luteum. Differences between species are expected in regards to SOD activity during the estrous or menstrual cycles and could explain some physiological species-specificities, namely concerning the endometrial cycle and the type and chronology of implantation. E.g., estrogen-mediated reduction in SOD activity, as described in the canine endometrium during the early luteal stage, may be associated with an increase in the membrane fluidity of endometrial cells and therefore be favorable to embryo invasion. In this chapter, we comprehensively investigate SOD effects in the homeostasis of mammal endometrium, using available information on several species and our team experience in the topic. In addition, we will also address its role in endometrial integrity and some uterine clinical conditions and infertility