The Role of Antioxidant Enzymes in the Ovaries

Abstract

Proper physiological function of the ovaries is very important for the entire female reproductive system and overall health. Reactive oxygen species (ROS) are generated as by-products during ovarian physiological metabolism, and antioxidants are indicated as factors that can maintain the balance between ROS production and clearance. A disturbance in this balance can induce pathological consequences in oocyte maturation, ovulation, fertilization, implantation, and embryo development, which can ultimately influence pregnancy outcomes. However, our understanding of the molecular and cellular mechanisms underlying these physiological and pathological processes is lacking. This article presents up-to-date findings regarding the effects of antioxidants on the ovaries. An abundance of evidence has confirmed the various significant roles of these antioxidants in the ovaries. Some animal models are discussed in this review to demonstrate the harmful consequences that result from mutation or depletion of antioxidant genes or genes related to antioxidant synthesis. Disruption of antioxidant systems may lead to pathological consequences in women. Antioxidant supplementation is indicated as a possible strategy for treating reproductive disease and infertility by controlling oxidative stress (OS). To confirm this, further investigations are required and more antioxidant therapy in humans has to been performed.

Figure 1

Schematic representation of reactive oxygen species (ROS) generation and important cellular enzymatic antioxidant pathways. The formation of ^•O₂ is the initial step in a cascade that results in the formation of other ROS. Mammalian cells contain a variety of antioxidant mechanisms to maintain ROS at a certain concentration. The major antioxidant enzymes include SOD, catalase, GSH, GPX, GR, and GST. These enzymes work together to form a defence system against ROS damage.

Figure 2

Schematic representation of antioxidant regulation in follicular development. The follicular development process is initiated with primordial follicles to primary follicles, followed by secondary follicles and tertiary follicles. Preovulatory follicles are formed under the stimulation of FSH, and finally, ovulation is triggered by a surge of luteinizing hormone (LH). All these consecutive and synchronized events are accompanied by ROS production and scavenging. Antioxidants are strongly modulated during this process. Catalase and GSH expression in the follicles is enhanced with follicular growth, while SOD activity is reduced in folliculogenesis. SOD was shown to have inhibitory effects on oestrogen synthesis by inhibiting FSH-induced aromatase activity in cultured granulosa cells, while SOD enzyme activity is positively correlated with oestradiol levels in the follicular fluid. A large amount of ROS can be produced during steroidogenesis, especially during the conversion of cholesterol to pregnenolone via cytochrome P450scc. Gonadotropin induces the upregulation of antioxidants such as catalase; GSH in the follicles protects oocytes from oxidative stress generated from physiological metabolic processes, such as steroidogenesis, in the ovary.