Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as “oxidative stress” that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus.

Diabetes mellitus and oxidative stress—A concise review

Infertility affects approximately 15% of couples trying to conceive, and a male factor contributes to roughly half of these cases. Oxidative stress (OS) has been identified as one of the many mediators of male infertility by causing sperm dysfunction. OS is a state related to increased cellular damage triggered by oxygen and oxygen-derived free radicals known as reactive oxygen species (ROS). During this process, augmented production of ROS overwhelms the body's antioxidant defenses. While small amounts of ROS are required for normal sperm functioning, disproportionate levels can negatively impact the quality of spermatozoa and impair their overall fertilizing capacity. OS has been identified as an area of great attention because ROS and their metabolites can attack DNA, lipids, and proteins; alter enzymatic systems; produce irreparable alterations; cause cell death; and ultimately, lead to a decline in the semen parameters associated with male infertility. This review highlights the mechanisms of ROS production, the physiological and pathophysiological roles of ROS in relation to the male reproductive system, and recent advances in diagnostic methods; it also explores the benefits of using antioxidants in a clinical setting.

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Effect of oxidative stress on male reproduction.

Oxidative stress (OS) has been considered a major contributory factor to the infertility. Oxidative stress is the result of imbalance between the reactive oxygen species (ROS) and antioxidants in the body which can lead to sperm damage, deformity, and eventually male infertility. Although high concentrations of the ROS cause sperm pathology (ATP depletion) leading to insufficient axonemal phosphorylation, lipid peroxidation, and loss of motility and viability but, many evidences demonstrate that low and controlled concentrations of these ROS play an important role in sperm physiological processes such as capacitation, acrosome reaction, and signaling processes to ensure fertilization. The supplementation of a cryopreservation extender with antioxidant has been shown to provide a cryoprotective effect on mammalian sperm quality. This paper reviews the impacts of oxidative stress and reactive oxygen species on spermatozoa functions, causes of ROS generation, and antioxidative strategies to reduce OS. In addition, we also highlight the emerging concept of utilizing OS as a tool of contraception.

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Impacts of Oxidative Stress and Antioxidants on Semen Functions

Male infertility accounts for up to half of the infertility cases and affects 13–15% couples worldwide. An optimal level of reactive oxygen species is crucial for maintaining spermatogenesis and sperm functions. However, excessive production of reactive oxygen species may cause oxidative stress. Oxidative stress has been identified as one of the major risk factors which affects the fertilizing potential of spermatozoa. Oxidative stress occurs due to excessive production of ROS and causes germ cell DNA damage, sperm fragility and defects in motility, culminating in infertility. Poor sperm quality and DNA damage may also result in pregnancy loss. This article highlights the significance of ROS in human male fertility and that of oxidative stress in infertility.

Oxidative stress and male infertility

Aerobic life requires organisms to resist the damaging effects of ROS (reactive oxygen species), particularly during stress. Extensive research has established a detailed picture of how cells respond to oxidative stress. Attention is now focusing on identifying the key molecular targets of ROS, which cause killing when resistance is overwhelmed. Experimental criteria used to establish such targets have differing merits. Depending on the nature of the stress, ROS cause loss of essential cellular functions or gain of toxic functions. Essential targets on which life pivots during ROS stress include membrane lipid integrity and activity of ROS-susceptible proteins, including proteins required for faithful translation of mRNA. Protein oxidation also triggers accumulation of toxic protein aggregates or induction of apoptotic cell death. This burgeoning understanding of the principal ROS targets will offer new possibilities for therapy of ROS related diseases.

Molecular targets of oxidative stress.

Vitamin E is one of the major membrane protectants against reactive oxygen species ( ROS) and lipid peroxidation (LPO). The study aimed at determining the optimum dose of vitamin E to reverse free radical-mediated oxidative damage on motility, viability and LPO of bulls’sperm. Fresh semen of five local crossbred bulls was suspended in 2.9% sodium citrate, divided into equal fractions and subjected to vitamin E treatment (0, 1, 2, 2.5 mM) in the presence or absence of oxidative stress inducer, i.e ferrous ascorbate (FeAA, containing 150 μM FeSO4 and 750 μM ascorbic acid). All sperm suspensions were incubated at 37°C for 2 h. Treatment with FeAA reduced sperm motility and viability, but increased the LPO. All doses of vitamin E increased sperm motility and viability, but reduced LPO. However, 2 mM vitamin E was most effective. In conclusion, vitamin E reduced the LPO caused by FeAA, and improved sperm motility and viability in vitro under induced oxidative stress.

Antioxidant effect of vitamin E on motility, viability and lipid peroxidation of cattle spermatozoa under oxidative stress

Reactive oxygen species (ROS) are generated by sperm metabolism. While, ROS are required for maturation, capacitation and acrosome reaction, they also modify many peroxidable cellular compounds. There is production of ROS during cryopreservation and frozen spermatozoa are highly sensitive to lipid peroxidation (LPO). Antioxidants exert a protective effect on the plasma membrane of frozen bovine sperm preserving both metabolic activity and cellular viability. Manganese (Mn(++)) is proved to be a chain breaking antioxidant in biological system. Therefore, we examined the role of (Mn(++)) during cryopreservation of cattle bull semen. Semen was divided into four parts and cryopreserved in egg-yolk-citrate extender + glycerol (EYC-G), EYC-G + 100 microM of Mn(++), EYC-G + 150 microM of Mn(++) and EYC-G + 200 microM of Mn(++). After four hours of cooling and 24 hrs of freezing, the spermatozoa were examined for percentage motility, Hypo-osmotic swelling (HOS), LPO and protein leakage. Addition of manganese to the semen during cryopreservation showed a protective effect and accounted for an increase in semen quality parameters [percentage motility, HOS percent and decrease in malondialdehyde (MDA) production and protein leakage]. The effect of manganese on motility and HOS was non-significant (p < 0.05) in cooled spermatozoa but significant with 150 microM of Mn(++) in frozen-thawed spermatozoa. MDA production and protein leakage decreased to a significant and maximum level (p < 0.05) on addition of 200 microM of manganese. The addition of manganese to EYC-G dilutor will improve the quality/fertility of semen, which will result in improvement of in vitro fertilization and artificial insemination success rate.

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Manganese provides antioxidant protection for sperm cryopreservation that may offer new consideration for clinical fertility.

Oxidative stress alters membrane sulfhydryl status, lipid and phospholipid contents of crossbred cattle bull spermatozoa

Ferrous ascorbate – FeAA (FeSO4 + ascorbic acid) – has been used in the past to induce oxidative stress. In this study, the effects of various doses of vitamin E (1 mM, 2 mM, 2.5 mM) and Mn2+ (60 μM, 100 μM, 200 μM) on total thiol (TSH), glutathione reduced (GSH), glutathione oxidized (GSSG), and redox ratio (GSH/GSSG) were determined in the local crossbred cattle bull spermatozoa. Fresh semen was suspended in 2.9% sodium citrate and the suspension was divided into eight equal fractions. All fractions, i.e. control (containing 2.9% sodium citrate + spermatozoa) and experimental, i.e. treated / untreated with ferrous ascorbate (150 μM FeSO4 : 750 μM ascorbic acid), supplemented / unsupplemented with three doses of vitamin E (1 mM, 2 mM, 2.5 mM) / Mn2+ (60 μM, 100 μM, 200 μM) were incubated for 2 h at 37°C. These fractions were used for thiol components assessment. By inducing oxidative stress, FeAA decreased the TSH and GSH levels and GSH / GSSG ratio, but increased the GSSG level. All doses of vitamin E and Mn2+ improved the TSH and GSH level and GSH / GSSG ratio, but decreased GSSG level under normal and oxidative stress conditions. It is concluded that oxidative stress treatment (FeAA) decreased (P≤0.05) TSH and GSH contents but maintained GSSG concentration and GSH/GSSG ratio unchanged (P≥0.05). However, supplementation with vitamin E increased (P≤0.05) both the GSH content and GSH/GSSG ratio, but Mn2+ increased (P≤0.05) the GSH content only.

Gurmail Singh Bilaspuri

Papers

Impacts of Oxidative Stress and Antioxidants on Semen Functions

Antioxidant effect of vitamin E on motility, viability and lipid peroxidation of cattle spermatozoa under oxidative stress

Manganese provides antioxidant protection for sperm cryopreservation that may offer new consideration for clinical fertility.

Oxidative stress alters membrane sulfhydryl status, lipid and phospholipid contents of crossbred cattle bull spermatozoa

Effect of vitamin E and Mn2+ on the thiol status of cattle bull spermatozoa under induced oxidative stress.