Editors' Formulation: Oxidative Stress in Gynecology

Abstract

Oxidative stress has been implicated in the pathogenesis of various diseases. Oxidative stress is a widely used term that generally refers to an imbalance in the rate at which the intracellular content of free radicals increases relative to the capacity of the cell to eliminate free radicals. Such stress is known to cause apoptosis and cell death in many different types of cells. It is still unknown what causes these cells to activate and produce these changes. However, recent evidence suggests that oxidative stress is important to the stimulation of cell division, gene expression, and cell death. As such, one can see the applicability of the information gained in the study of atherosclerosis to many chronic, inflammatory disease processes. The study of oxidative stress in reproductive diseases is in its infancy. Gynecologic disorders have not received the attention of scientists knowledgeable in this field until recently. The presence of various oxidative/antioxidant systems in a number of reproductive tissues has sparked an interest in their study. The application of molecular techniques and the availability of molecular probes for oxidative enzymes will advance our knowledge significantly. Given these new tools, there has been a renewed interest in studying the role of oxidation in diseases well known to be associated with increased oxidative stress as well as reproductive disorders. The issue deals with some of the aspects relating oxidation to several disorders of women. It will be years before conclusive proof is available for an etiologic role of oxidation in some of these diseases; however, we hope this issue will introduce a topic which is not widely appreciated in gynecology. More importantly, we hope it will also impart the excitement of those of us working in this field as we take information gained from the study of atherosclerosis and apply it to explain reproductive physiology and pathophysiology. In their article on oxygen radicals, antioxidants, and lipid peroxidation, Drs. Santanam, Ramachandran and Parthasarathy, give a general overview of the generation and reactions of oxygen free radicals and several methodologies to detect these free radicals. Dr. Parthasarathy is an international authority in free radical biology and was instrumental in formulating the theory of oxidative stress and atherosclerosis. Dr. Neil Hogg has elaborated the role of oxygen free radicals in various diseases and in particular the role of nitric oxide. Studies have indicated that nitric oxide plays an important role in disorders such as preeclampsia and ovarian disjunction. Free radicals have been implicated in aging, cancer, inflammation/sepsis, and neurodegenerative disorders such as Alzheimer's disease. Atherosclerosis, is an inflammatory disorder. The role of oxidation has been well established in this disease. It serves as the basis for the majority of our knowledge of oxidation. Knowledge gained from the study of atherosclerosis has been the basis of much of our study of other diseases of oxidative stress. Dr. Rosenfeld in his article concerning lessons learned from the atherogenic process describes the role of oxidation in this disorder. Estrogen plays a major role in female physiology. Obstetrician/gynecologists and especially reproductive endocrinologists have failed to consider other roles of estrogen besides its role as a reproductive hormone. Estrogens and progesterone derivatives have been found to have nongenomic actions. In Chapter 4, Drs. Nathan and Chaudhuri explore the role of estrogen as an antioxidant/ prooxidant in women's diseases. Cardiovascular disease affects women most after the menopause. It is the most common cause of death in women. Estrogen has been suggested to be cardioprotective in younger women. Atheroscler-