Roles of antioxidant enzymes in corpus luteum rescue from reactive oxygen species-induced oxidative stress

Abstract

Progesterone produced by the corpus luteum (CL) regulates the synthesis of various endometrial proteins required for embryonic implantation and development. Compromised CL progesterone production is a potential risk factor for prenatal development. Reactive oxygen species (ROS) play diverse roles in mammalian reproductive biology. ROS-induced oxidative damage and subsequent adverse developmental outcomes constitute important issues in reproductive medicine. The CL is considered to be highly exposed to locally produced ROS due to its high blood vasculature and steroidogenic activity. ROS-induced apoptotic cell death is involved in the mechanisms of CL regression that occurs at the end of the non-fertile cycle. Luteal ROS production and propagation depend upon several regulating factors, including luteal antioxidants, steroid hormones and cytokines, and their crosstalk. However, it is unknown which of these factors have the greatest contribution to the maintenance of CL integrity and function during the oestrous/menstrual cycle. There is evidence to suggest that antioxidants play important roles in CL rescue from luteolysis when pregnancy ensues. As luteal phase defect impacts fertility by preventing implantation and early conceptus development in livestock and humans, this review attempts to address the importance of ROS-scavenging antioxidant enzymes in the control of mammalian CL function and integrity. The corpus luteum (CL) is a transient endocrine organ that develops after ovulation from the ovulated follicle during each reproductive cycle. The main function of the CL is the production and secretion of progesterone which is necessary for embryonic implantation and development. Compromised CL progesterone production is a potential risk factor for prenatal development and pregnancy outcomes. Reactive oxygen species (ROS), which are natural by-products of cellular respiration and metabolism, play diverse roles in mammalian reproductive biology. ROS-induced oxidative damage and subsequent development of adverse pregnancy outcomes constitute important issues in reproductive medicine. Before the end of the first trimester, a high rate of human and animal conceptions end in spontaneous abortion and most of these losses occur at the time of implantation in association with ROS-induced oxidative damage. Every cell in the body is normally able to defend itself against the oxidative damage caused by the ROS. The cellular antioxidant enzymes constitute the first line of defence against the toxic effects of ROS. The CL is considered to be highly exposed to locally produced ROS due to its high blood vasculature and metabolic activity. There is now evidence to suggest that cellular antioxidants play important roles in CL rescue from regression when pregnancy ensues. As defective CL function impacts fertility by preventing implantation and early conceptus development in livestock and humans, this review attempts to address the importance of antioxidant enzymes in the control of mammalian CL function and integrity.

Effects of IL8 and immune cells on the regulation of luteal progesterone secretion

“…These observations support our earlier findings (Liptak et al 2005) that activated immune cells may contribute a factor (or factors) that impair steroidogenesis in response to LH. It is known that activated monocytes produce inflammatory cytokines, nitric oxide, and reactive oxygen species (Murray & Wynn 2011, Zhou et al 2014) all of which may contribute individually or in combination to the inhibition of progesterone synthesis (Al-Gubory et al 2012, Quirk et al 2013, Skarzynski et al 2013). In the in vivo setting, activated monocytes may also secrete matrix metalloproteinases that contribute to the degradation of the extracellular matrix (Murray & Wynn 2011), which could facilitate the recruitment of additional inflammatory cells to the regressing corpus luteum.…”

Reactive oxygen species and antioxidant defense in human gastrointestinal diseases

“…Despite this, it has been shown that mitochondria generate ROS at an amount higher than their scavenging capacity 8 . O 2 • — is initially formed via a large number of pathways, including normal cellular respiration, the metabolism of arachidonic acid by lipoxygenases and cyclo-oxygenases and from inflammatory and endothelial cells 9 . The main sources of O 2 • — are respiratory complexes I (NADH dehydrogenase) and III (ubisemiquinone) located at the inner mitochondrial membrane, which generate a small amount of O 2 • — as a side product of electron transport during oxidative phosphorylation 10 .…”

“…Without O 2 • — , the formation of nitrogen dioxide by the reaction of NO with oxygen is miniscule by comparison. There is no requirement for NO and O 2 • — to be produced within the same cell to form peroxinitrite, as NO can readily move through membranes and between cells 9, 21…”

“…The primary antioxidant enzymes against superoxide radicals include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). These enzymes act together in the metabolic pathway of ROS, and altered activity of one enzyme without compensatory changes in others may lead to lipid peroxidation 9, 22, 23…”

Oxidative Stress in Unexplained Female Infertility

“…ROS target the pathway and also act as second messengers in some reactions [22]. ROS are known to effect ovulation and implantation [23].…”