The State of the LPO-AOD System and the Relative Length of Telomeric Repeats in the Chromosomes of Blood Leukocytes in Obstructive Sleep Apnea Syndrome.

We analyzed the relative length of telomeric repeats in peripheral blood leukocytes and indicators of oxidative stress in 32 men (mean age 51.2±3.1 years) with obstructive sleep apnea syndrome (OSAS). The control group consisted of volunteers without OSAS. The relative length of telomeres was determined in a DNA sample isolated from venous whole blood samples. The length of telomeric repeats of chromosomes was determined using quantitative real-time PCR (3 times for each DNA sample); albumin served as an internal control. The intensity of LPO processes and antioxidant protection was assessed by conventional spectrophotometric methods. It was found that in patients with OSAS, the relative length of telomeric repeats was lower by 48%, the levels of substrates and products of LPO were higher (double bonds and diene conjugates by 34 and 19%, respectively), and antioxidant protection indicators were lower (concentrations of fat-soluble vitamins α-tocopherol and retinol by 18 and 19.3%, respectively, total antioxidant activity by 32.9%) than in volunteers of the control group. Thus, we can conclude that the nucleotide sequences are reduced in patients with OSAS under conditions of intensified free radical oxidation.

Length of Leukocyte Telomeres in Newborns of HIV-Infected Mothers.

We studied the relative length of telomeres in newborns with unrealized perinatal transmission of HIV (zero viral load according to PCR results). A cross-sectional survey of 62 newborns of HIV-infected mothers (Apgar score 8); the control group consisted of 80 healthy newborns (Apgar score 8). DNA extracted from whole venous blood samples was analyzed. In newborns of HIV-infected mothers, the relative length of telomeres was significantly lower (0.69 (0.66; 0.72)) than in newborns of the control group (1.1 (0.97; 1.22)) (p<0.001). No significant differences in the relative length of telomeres were found between newborns of mothers with a viral load at the time of delivery and with undetectable viral load: 0.69 (0.66; 0.73) and 0.69 (0.63; 0.72). These findings indicate that HIV-infection in mothers or exposure to antiretroviral therapy has an impact on the relative telomere length in leukocytes of newborns.

[Activity of the telomerase complex before and after CPAP therapy in patients with obstructive sleep apnea syndrome]. / Aktivnost' telomeraznogo kompleksa na fone SIPAP-terapii u patsientov s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG1), n=35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG2) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent. RESULTS: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG1, after treatment it was 0.07 (0.06; 0.09) in the MG2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG1 and MG2. CONCLUSION: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

Features of the Free Radical Oxidation Process and Antioxidant System in Newborns Born to HIV-Infected of Mothers Who Received Antiretroviral Therapies to Prevent HIV Transmission.

The LPO processes and the state of the antioxidant system in perinatally HIV-exposed newborns were studied. Perinatally HIV-exposed (n=62) and healthy newborns (n=80; control) were examined retrospectively (Apgar score 8 in both groups). Blood plasma and erythrocyte hemolysate were used as the material for biochemical tests. Using spectrophotometric, fluorometric, and statistical methods, we found enhanced LPO processes insufficiently compensated by the antioxidant system with excessive accumulation of damaging metabolites in the blood of perinatally HIV-exposed newborns. These changes can be a consequence of oxidative stress during the perinatal period.

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.

[Changes in the telomeres length in patients with obstructive sleep apnea after continuous positive airway pressure therapy: a pilot study]. / Izmenenie otnositel'noi dliny telomer u patsientov s sindromom obstruktivnogo apnoe sna na fone SIPAP-terapii: pilotnoe issledovanie.

OBJECTIVE: To evaluate a relative telomere length in patients with obstructive sleep apnea (OSA) before and after a 6-month course of continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: Seventy-five men participated in the study, including 50 men with OSA (the main group 1) and 25 men without OSA (the control group). The average age in the total group was 53.4±3.6 years. Thirty-five men completed the study (the main group 2). According to the design, night polysomnography (PSG) was performed for all the subjects, blood sampling to assess the length of telomeres was carried out in the morning according to the standard method. The values of the relative telomere length were obtained using the difference between the values of the threshold cycles for telomeric DNA and the reference gene albumin (∆CCt). After clarifying the diagnosis, CPAP was applied for 6 months. RESULTS: Statistically significant indicators of PSG were revealed: a decrease in NREM 3 in patients with OSA compared to controls (89.3±15.8 versus 150±23.4 minutes), an increase in NREM1-2 in OSA (296.2±31.1 and 170.1±24.5, respectively), REM was 84.6±15.4 in the main group and 118.5±19.5 in the control group. CPAP therapy conducted for 6 months (at least 4-5 nights a week, lasting at least 5-6 hours of night sleep) demonstrated a significant improvement in the qualitative and quantitative parameters of sleep. In patients of the main group 1, there is a shortening of the telomere length compared with the control group (p<0.001). With the elimination of hypoxia and improvement of the structure of sleep after CPAP, there was an increase in the telomere lengths in the main group 1 from 0.28 [0.24-0.29] to 0.32 [0.30-0.34] in the main group 2 (p=0.03). The telomers length in the control group was 0.53 [0.50-0.55]. CONCLUSION: Intermittent hypoxia and fragmentation of sleep in OSA leads to shortening of telomeres. CPAP, by eliminating the pathophysiological triggers of OSA, contributes to an increase in telomeres lengths and can slow down the premature aging in OSA.

[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.

Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.

Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.

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.

Free Radical Oxidation of Lipids as an Indicator of the Effectiveness of CPAP Therapy in Apnea Syndrome.

The processes of free radical lipid oxidation were studied in 47 patients with moderate to severe obstructive sleep apnea syndrome before and after 1-month course of CPAP-therapy (continuous positive airway pressure). The control group consisted of 13 people without clinically confirmed apnea. The material for the study was serum, blood plasma, and erythrocyte hemolysate. The levels of LPO products and antioxidant defense were determined spectrophotometrically and spectrofluorometrically. The changes revealed in patients with obstructive sleep apnea syndrome after CPAP therapy indicate a decrease in the intensity of LPO and restoration of the balance in the "LPO-antioxidant defense" system.

Changes in the Lipid Peroxidation-Antioxidant Protection System in Women with Ovarian Hyperandrogenism at Different Periods of Reproductive Age.

We studied changes in LPO processes and antioxidant protection system in women with ovarian hyperandrogenism at various periods of reproductive age 18-45 years. An age-related decrease in total antioxidant activity and accumulation of secondary LPO products, ketodiens and coupled trienes, were found; these changes were accompanied by an increase in the level of superoxide dismutase and a decrease in the concentrations of reduced glutathione, α-tocopherol, and retinol. Women of early reproductive age (18-35 years) with hyperandrogenism were characterized by increased content of oxidized glutathione accompanied by a decrease in the level of α-tocopherol and retinol in comparison with the control group. In women of late reproductive age (35-45 years) with hyperandrogenism, increased superoxide dismutase activity in comparison with the control group was revealed.

[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.

Heat Shock Protein HSP70 in Oxidative Stress in Apnea Patients.

We studied the level of heat shock protein HSP70 under conditions of oxidative stress in 47 patients with apnea. The control group included 13 healthy subjects without verified apnea. Blood serum, plasma, and erythrocyte hemolysate were used to determine LPO and anti-oxidant protection components by spectrophotometrical and spectrofluorometrical methods. HSP70 was assayed by ELISA. A direct relationship was established between the intensity of oxidative stress and HSP70 expression in patients with apnea. Quantitative determination of HSP70 can be used as a molecular marker in the early diagnosis and prognosis of the development of various pathological conditions in hypoxia.

[Expression of heat shock proteins HSP70 under oxidative stress.]

Developing oxidative stress inevitably causes damage to cell proteins in need of timely refolding. Synthesis of a group of heat shock proteins is the most ancient and effective mechanism of cell protection. In the course of the whole life of the cell adaptation to a huge number of cytotoxic factors, both xenobiotic and natural origin provide heat shock proteins with polyfunctionality and in terms of the implementation of programmed death acting as either anti - or proapoptogenic factors, or as regulators of the activity of these factors. Studies show the important role of heat shock proteins in adaptation, inflammation, and immune response. Various experimental and clinical studies prove the important role of heat shock proteins in the development of pathophysiological phenomena of oxidative stress, aging, tumor formation, immune reactions. Presented in the review data of domestic and foreign studies on the physiological significance of heat shock proteins, their role in the mechanisms of cell and body stability in General are relevant to modern medicine and biology.

[The association of GSTP1 polymorphisms with male idiopathic infertility].

AIM: To identify the association between Ile105Val, Ala114Val polymorphisms of gene GSTP1 (glutathione transferase pi1) and infertility in Russian men. MATERIALS AND METHODS: A total of 160 infertile Russian men of reproductive age (mean age 30.2+/-3.6 years) were included in study group, while in control group there were 104 age-matched healthy fertile Russian male (mean age 31.3+/-5.4 years). Molecular and genetic studies of Ile105Val, Ala114Val polymorphisms of gene GSTP1 were performed using real-time polymerase chain reaction. Genomic DNA was extracted from the peripheral blood. RESULTS: A frequency of genotypes (p=0.024; df=2; p=0.024) and alleles (z=2,778; p=0,005) of Ile105Val locus was significantly different in the study and control group. In the study group, there was an increase in the frequency of the Ile/Ile genotype by 13% (=3.995; df=1; p=0.046) and a decrease in the frequency of the Val/Val genotype by 6% (=4.887; df=1; p=0.027). A rate of genotype Ile/Ile in infertile men with was 1.7 time higher than in control group (odds ratio (OR):1.73; 95% confidence interval (Cl): 1.04-2.87; p<0.05). There was not significant difference in frequency of genotypes and alleles of Ala114Val polymorphism of gene GSTP1 between the study and control groups. CONCLUSIONS: The male infertility in Russia is associated with Ile105Val polymorphism and not associated with Ala114Val polymorphism of gene GSTP1. In infertile men wild-type genotype and major allele Ile105Val polymorphism of gene GSTP1 were significant more frequent compared to control group. A rate of genotype Ile/Ile in men with infertility was 1.7 time higher.

[Oxidative stress in some inflammatory and infectious urogenital diseases in men].

The article summarizes and analyzes the literature relating to lipid peroxidation and antioxidant protection in men with infectious and inflammatory diseases of diverse etiologies. These processes not only impair spermatogenesis, but also result in the oxidative stress in the blood and semen of men of reproductive age. Analysis of recent domestic and international literature suggests that oxidative stress is a key contributor and/or one of the pathogenetic links in the development of many infectious urogenital diseases 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.