Roles of Reactive Oxygen Species and Antioxidants in Ovarian Toxicity1

Proper functioning of the ovary is critical to maintain fertility and overall health, and ovarian function depends on the maintenance and normal development of ovarian follicles.This review presents evidence about the potential impact of oxidative stress on the well-being of primordial, growing and preovulatory follicles, as well as oocytes and early embryos, examining cell types and molecular targets.Limited data from genetically modified mouse models suggest that several antioxidant enzymes that protect cells from reactive oxygen species (ROS) may play important roles in follicular development and/or survival.Exposures to agents known to cause oxidative stress, such as gamma irradiation, chemotherapeutic drugs, or polycyclic aromatic hydrocarbons, induce rapid primordial follicle loss; however, the mechanistic role of ROS has received limited attention.In contrast, ROS may play an important role in the initiation of apoptosis in antral follicles.Depletion of glutathione leads to atresia of antral follicles in vivo and apoptosis of granulosa cells in cultured antral follicles.Chemicals, such as cyclophosphamide, dimethylbenzanthracene, and methoxychlor, increase proapoptotic signals, preceded by increased ROS and signs of oxidative stress, and cotreatment with antioxidants is protective.In oocytes, glutathione levels change rapidly during progression of meiosis and early embryonic development, and high oocyte glutathione at the time of fertilization is required for male pronucleus formation and for embryonic development to the blastocyst stage.Because current evidence suggests that oxidative stress can have significant negative impacts on female fertility and gamete health, dietary or pharmacological intervention may prove to be effective strategies to protect female fertility.follicle, oocyte, ovary, oxidative stress, toxicology REACTIVE OXYGEN SPECIES AND OXIDATIVE STRESSReactive oxygen and nitrogen species (ROS and RNS, respectively) include superoxide anion radicals, hydroxyl radicals, hydrogen peroxide (H 2 O 2 ), peroxynitrite and other peroxides, nitric oxide, and others (Fig. 1).ROS are formed through leakage of electrons from the inner mitochondrial membrane during oxidative phosphorylation and ATP generation.In steroidogenic tissues such as the ovary, steroidogenic cytochrome P450 enzymes are also sources of ROS [1,2].Oxidative and nitrosative damage occur when ROS and RNS react with cellular lipids, proteins, and nucleic acids [3][4][5].The redox (reduction-oxidation) state of a cell describes the relative concentrations of reduced versus oxidized states of proteins, enzymes, sulfhydryl-containing molecules, and other factors.The relationship between intracellular levels of ROS relative to endogenous antioxidants has a significant impact on this measure.Oxidative stress occurs when increased ROS levels disrupt cellular redox circuits, resulting in disturbances of redox-regulated cellular processes and/or oxidatively damage cellular macromolecules [6,7]. ANTIOXIDANT DEFENSE MECHANISMSMultiple enzyme systems and soluble factors maintain the redox state of cells.Some of these are shown in Figure 1.The antioxidant defense mechanisms in cells are complex and appear to be compartmentalized, such that nuclear, cytoplasmic, and mitochondrial levels of antioxidants behave independently [8,9].Ascorbate (vitamin C), present at millimolar levels in ovarian cells and at 50-200 micromolar in human follicular fluid [10,11], reacts directly with ROS to detoxify them, as do tocopherols (vitamin E).Ascorbate is concentrated in granulosa cells, theca cells, luteal cells, and the oocyte, and its uptake is hormonally regulated [10][11][12][13][14]. Glutathione (GSH), a cysteine-containing tripeptide, is another key antioxidant present in millimolar concentrations in cells.It can scavenge free radicals through either direct chemical reactions or reduction of peroxides as a cofactor for GSH peroxidases, cycling between its reduced form (GSH) and an oxidized, dimerized form (GSSG) [15,16].The activity of GSH

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.