Oxidative Stress, Telomere Length and Telomerase Activity in Spermatogenesis Disorders (Review of Scientific Activity).

The paper systematizes the available data on the study of oxidative stress, the relative length of telomeres, and telomerase activity in male infertility and disorders of spermatogenesis. The study of telomeres, the structures that protect chromosome ends and genome integrity, is of interest for researchers in various fields, from cell biology and epidemiology to ecology and evolutionary biology. The review includes our own data on the study of the relative length of telomeres, oxidative stress, and telomerase activity and reflects modern ideas about the importance of these structures both in the maintenance of genome stability during cell division and in gametogenesis and reproduction. Many studies indicate the role of oxidative stress in the pathogenesis of various diseases, including male infertility. In turn, studies of telomeres as a biomarker of male infertility are insufficient, and the results obtained are extremely controversial and require deeper knowledge about the mechanisms underlying the dynamics of telomere length.

Changes in Spermatogenesis, Lipoperoxidation Processes, and Antioxidant Protection in Men with Pathozoospermia after COVID-19. The Effectiveness of Correction with a Promising Antioxidant Complex.

The indicators of spermatogenesis and the state of LPO and antioxidant protection in men with pathozoospermia after COVID-19 were assessed before and after treatment an antioxidant complex. Blood plasma served as the material for biochemical studies. In the examined patients, the parameters of spermatogenesis, as well as blood concentration of LPO components (diene conjugates and TBA-reactive substances) were analyzed. The total antioxidant activity of the blood was determined as an indicator characterizing the total activity of LPO inhibitors and determining its buffer capacity. In patients recovered from COVID-19, an increase in spermatogenesis disorders and shifts towards the predominance of prooxidant factors were observed. After a course (1 month) of antioxidant complex, patients showed increased sperm motility, decreased leukocyte count in the ejaculate, and restored balance in the prooxidant-antioxidant system towards antioxidant components. The effectiveness of correction of post-COVID disorders largely depends on the degree of damage to the structure and function of cell membranes caused by oxidative stress. The use of the antioxidant complex is a promising option, because it reduces the level of LPO, enhances antioxidant protection of the body, and also normalizes some parameters of spermatogenesis.

[Male reproductive health and COVID-19].

The SARS-CoV-2 pandemic has brought serious economic and social problems worldwide'. Due to its medical consequences, it is of importance to study the mechanisms of the disease and new therapeutic interventions, as well as rehabilitation processes. Despite the fact that the genome of the new coronavirus has been sequenced and studied, clinical and epidemiological data are constantly updated and analyzed, and exact pathogenesis has not yet been understood. At the same time, domestic and foreign studies suggest that the virus is an agent that affects not only the lungs, vascular wall, hemostasis, but also the reproductive system. The aim of the review is to summarize the current knowledge about novel SARS-CoV-2, including its pathophysiology and potential impact on male reproductive function.

[Disorders of lipid metabolism as a risk factor for male infertility].

The presented literature review analyzes and summarizes data on studies by domestic and foreign authors on one of the most pressing problems of modern andrology - the pathogenetic relationship of excess body weight and male infertility. Modern clinical, epidemiological and experimental data indicate a negative effect of obesity on the reproductive function of men. According to the WHO, in Russia 54% of men are overweight, 15% of whom are obese. The problem of obesity is independent of age, area of residence, as well as the social and professional level of men. Obesity is a predisposing factor in the development of concomitant somatic pathological processes. Oxidative stress of sperm, androgen deficiency, neuropathy is far from an exhaustive list of the most important mechanisms for the realization of the neuroendocrine and reproductive effects of overweight and obesity. The increasing number of infertile couples annually dictates the need for a reliable monitoring system to get a correct picture of the development of the obesity epidemic, as well as to quickly assess what preventive measures should be taken.

Indicators of the Lipid Peroxidation-Antioxidant Protection System as Important Metabolic Markers of Reproductive Potential in Men.

We analyze results of recent studies demonstrating unfavorable state of the reproductive health in the male population that manifested not only in spermatogenesis deterioration, but also in oxidative stress (both systemic and in seminal fluid). The data on the effect of ROS and components of the antioxidant defense system on gamete quality in men with infertility associated with obesity and diabetes mellitus are presented. Some features of oxidative stress in men of reproductive age of various ethnic groups are shown. Evaluation of the parameters of oxidative stress provides new insight into the molecular mechanisms of functional activity of the semen and may become a promising direction for the development of new methodological recommendations for personalized diagnosis, prevention, and correction of reproductive disorders in men.

[Association of polymorphic markers of GSTP1 gene with oxidative stress parameters in infertility men].

Genetic factors cause various forms of male infertility in 30-50% of cases. The role of oxidative stress in male infertility has been broadly recognised, and the search for a new marker to determine the redox environment in semen has gained considerable interest. AIM: to establish the association of two polymorphic loci Ile105Val, Ala114Val of the GSTP1 gene (glutathione transferase class pi-1) with the parameters of oxidative stress in men with infertility. MATERIALS AND METHODS: the main study group consisted of 160 men of reproductive age with infertility (mean age - 29,9+/-5,3 years). The control group included 104 practically healthy men with realized reproductive function (average age - 30,2+/-3,6 years). Molecular and genetic study of polymorphisms of the GSTP1 gene was performed by using real-time PCR. The material for the study was DNA samples, the extraction of which was carried out from samples of whole venous blood. The components of lipid peroxidation and antioxidant protection were determined in the blood and ejaculate using spectrophotofluorometric METHOD: s. Resalts: While analyzing the frequency of occurrence of the Ile105Val polymorphism of the GSTP1 gene in men with infertility and fertile men, statistically significant differences were found at (2=7,487; p=0,024). No significant differences were found between the groups (2=3,823; p=0,14), when were compared the frequency distribution of the genotypes of the Ala114Val polymorphism of the GSTP1 gene in men diagnosed with infertility and fertile patients. In men with infertility, carriers of the GSTP1(Ile105Val) heterozygous polymorphism, associations of the studied gene were established with an increase in GSH activity by 7% and a decrease in GR by 20% in blood and a decrease in SOD activity by 8% in the ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(Ile105Val), which have associations with an increase in total AOA blood by 20% and with a decrease in GPO activity by 24% in the ejaculate. In men with infertility, carriers of the heterozygous polymorphism of GSTP1(Ala114Val), associations of the studied gene were established with a decrease in -tocopherol concentration by 15%, an increase in GPO activity by 25% in blood and a decrease in SOD activity by 7% in ejaculate, in contrast, fertile men, carriers of heterozygous polymorphism GSTP1(l114Val), which have associations with an increase in the concentration of DK in blood by 19% and with a decrease in GST activity by 32% in the ejaculate. CONCLUSION: identification of carriers of polymorphic loci Ile105Val, Ala114Val GSTP1, as well as determination of enzymes of the thiol disulfide system can be recommended for additional assessment of the risk of reproductive disorders in men.

Role of Glutathione-S-Transferase Family Genes in Male Infertility.

Polymorphisms of xenobiotic detoxification genes GSTT1 and GSTM1 and activity of glutathione system enzymes were studied in men with infertility. The frequency of deletion variant of GSTT1 gene in men with infertility was by 2 times higher than in fertile men. Deletion variant of GSTM1 gene was 1.4-fold more frequent in infertile men than in fertile men. Complete deletion of two genes was found in 19% men with infertility and only in 6% fertile men. The balance of activity of glutathione system enzymes essential for the effective detoxification of exogenous xenobiotics and toxic endogenous metabolites was impaired in infertile carriers of deletion variants of genes. Our results suggest that adaptation mechanisms are disordered in infertile men.

Features of Lipoperoxidation, Antioxidant Defense, and Thiol/Disulfide System in the Pathogenesis of Infertility in Males, Carriers of Nonfunctional Variants of GSTT1 and GSTM1 Gene Polymorphisms.

Comparative analysis of the parameters of LPO, antioxidant defense (AOD), and the thiol/disulfide system was performed in fertile and infertile males of reproductive age carrying different genotypes of the glutathione system genes. Blood plasma, blood hemolysate, and ejaculate served as specimens for biochemical studies. A decrease in glutathione S-transferase activity was found in blood and ejaculate specimens from fertile and infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes. In infertile carriers of nonfunctional GSTT1(0/0)/GSTM1(0/0) genotypes determining reduced glutathione S-transferase activity, a decrease in the concentration of low-molecular-weight cell antioxidant (reduced glutathione) and an increase in the concentration of secondary LPO products (TBA-reactive substances) were revealed. Identification of carriers the polymorphic GSTT1 and GSTM1 variants and analysis of activity of the thiol/disulfide system enzymes can be recommended for additional evaluation of the risk for reproductive dysfunction in men.

[Association of polymorphism of GSTT1 and GSTM1 genes with infertility in men].

AIM: To identify the association between homozygous deletion genotypes of glutathione transferase genes GSTT1 (glutathione transferase theta 1), GSTM1 (glutathione S-transferase mu1) and infertility in Russian men. MATERIALS AND METHODS: The article presents a comparative analysis of the incidence of homozygous deletion genotypes of glutathione transferase genes GSTM1 and GSTT1 in Russian men with and without infertility. The study group comprised 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years.) The infertility diagnosis was verified according to the WHO guidelines. The control group comprised 104 healthy Russian volunteers (mean age 31.3+/-5.4 years.) Molecular genetic detection of GSTM1 and GSTT1 deletion polymorphisms was performed using PCR. The genomic DNA for the study was extracted from whole blood samples. RESULTS: The study and control group differed significantly in incidence of GSTM1 (p=0.043) and GSTT1 (p=0.008) deletion polymorphisms. The probability of detecting "zero" genotypes of the GSTT1 and GSTM1 genes in infertile men was 2.5 (p<0.05) and 1.7 times higher (p<0.05), respectively, than in fertile men. CONCLUSIONS: Therefore, the study findings allow us to conclude that the deletion genotypes of GSTM1 and GSTT1 are associated with infertility in Russian men. Molecular genetic analysis of deletion polymorphism of glutathione transferase genes can be recommended for a comprehensive examination of infertile men.

Reproductive Health and Peculiarities of Lipid Peroxidation-Antioxidant Defense System in Men of the Main Ethnic Groups of the Baikal Region.

Quality of sperm and some parameters of LPO reflecting primary and end stages of oxidation and levels of α-tocopherol and total antioxidant activity were studied in ejaculate samples from 130 men (mean age of 24 years) living in Ulan-Ude, Buryatia Republic. All participants took a part in survey and were examined by an andrologist. The observed peculiarities of LPO and antioxidant defense in Russian men, such as decreased level of substrate supply for the processes of LPO and α-tocopherol, attest to specificity of metabolic processes and development of compensatory reactions of the organism under physiological conditions. LPO processes were more active in Buryat men, which can indicate exposure of cell membranes to toxic oxygen species. However, the observed in these patients significant increase in α-tocopherol concentration reflects adequate functioning of the adaptive and protective mechanisms of the body.

Parameters of Pro- and Antioxidant Status in Ejaculate of Men of Fertile Age.

Parameters of LPO reflecting primary and end stages of oxidation and total antioxidant activity were evaluated in the seminal fluid of young fertile men living in Novosibirsk. By the results of andrological examination and spermogram analysis, various reproductive disorders and abnormal spermogram (pathospermia) were found in 48 patients. Shifts towards activation of prooxidant processes in LPO-antioxidant defense metabolic system were observed in men with reproductive disorders and pathospermia. The results of individual estimation of coefficient of oxidative stress, an integral parameter reflecting the balance in the LPO-antioxidant defense system, attest to the development of oxidative stress in men with reproductive disorders and pathospermia.

[Glutathione-dependent enzymes and glutathione in infertility of men with different body mass].

OBJECTIVE: Our aim was to investigate the glutathione-disulfide system of antioxidant defense in men with different body mass index and infertility. METHODS: 60 men with infertility were examined--30 with normal weight and 30 with overweight. 30fertile men were included in the control group. Hemolysate made from red blood cells was used as a materialfor study. The level of reduced (GSH) and oxidized glutathione (GSSG), and glutathione activity was determined by enzyme spectrofluorophotometer SHIMADZU-1501 (Japan). RESULTS: In infertile men with normal body weight decrease of GSH to 15.35% was combined with a decrease in the activity of enzymes--glutathione reductase (GR) to 53.41%, glutathione peroxidase (GPO) to 51.44%, and increased activity of glutathione-S-transferaze (GST) to 31.52% as compared with the controlgroup. In the group of infertile men with overweight a decrease in the activity of GR, 56.77% and 56.22% at the GPO on the background of a stable level of GST was detected in comparison with fertile men. The concentration of GSH in infertile group decreased by 20.08%, and the concentration of GSSG increased by 20.38%. CONCLUSION: It has been established that imbalance in the glutathione system is the most prominent feature in men with infertility and overweight as compared to infertile men with normal body weight.