The purpose of this study was to assess the association of two polymorphic loci Ile105Val/Ala114Val of the GSTP1 gene with the parameters of oxidative stress (OS) in men with infertility. We retrospectively analyzed the results of a survey of 222 men (mean age of 29.9 +/- 5.3 years) of infertile couples. A control group of 104 men (30.2 +/- 3.6 years) was formed, consisting of healthy men with realized reproductive function. An analysis of the frequency with which the Ile1051Val polymorphism of the GSTP1 gene occurred in men with infertility and in fertile men found statistically significant differences (chi(2)=7.487; P=0.024). When comparing the frequency distribution of the genotypes of the Ala114Val polymorphism of the GSTP1 gene in infertile men and fertile patients, no significant differences were found between the groups (chi(2)=3.823; P=0.14). In men with infertility, carriers of the heterozygous genotype of the GSTP1 Ile105Val polymorphism presented an increase in reduced glutathione activity by 7% (P=0.0004), a decrease in glutathione reductase activity by 20% (P=0.03) in serum, and a decrease in SOD activity by 8% (P=0.01) in the ejaculate, unlike fertile men with heterozygous polymorphism, who had an increase in the total antioxidant activity of the blood serum by 20% (P=0.0001) and a decrease in glutathione peroxidase activity by 24% (P=0.03) in the ejaculate. In men with infertility, carriers of the heterozygous genotype of the GSTP1 Ala114Val polymorphism presented a decrease in a-tocopherol concentration by 15% (P=0.002), an increase in glutathione peroxidase activity by 25% (P=0.0004) in the blood and a decrease in SOD activity by 7% (P=0.01) in the ejaculate, unlike fertile men with heterozygous polymorphism, who had an increase in the concentration of serum conjugated dienes by 19% (P=0.0001) and a decrease in glutathione-S-transferase activity by 32% (P=0.03) in the ejaculate. Carrier identification of the GSTP1 Ile105Val and Ala114Val polymorphic loci, as well as the determination of the enzymes of the thiol-disulfide system, can be recommended for an additional assessment of the risk of developing reproductive disorders in men.
Stress reaction of the organism is a process occurring at the cellular, tissue and systemic levels. The organism responds to any adverse effect with a multi-level reaction, which causes the development of stress and, as a result, adaptation. The damaging effect is due to the excessive strengthening of another adaptive effect – lipotropic, that increases the activity of phospholipases and the intensity of free radical oxidation of lipids through the catecholamines and protein kinases. The changes in the immune system during the adaptation stage are to maintain antigenic homeostasis of the internal environment of the organism due to lymphoid cells, lymphocytes and cytokines. Almost all cells with antigen representation function are capable to produce interleukins under certain conditions. The vascular system is a kind of an indicator of any pathological process, determining the state of regulatory and adaptive mechanisms, the features of the connective tissue matrix. Stress causes a restructuring of metabolism and physiological functions, which increases the organism’s resistance to acute death. Thus, the physiological meaning of the stress reaction is the emergency mobilization of energy and structural resources of the organism and the creation of positive background for the implementation of reactions, aimed at maintaining homeostasis in extreme situations.
В статье приводится обзор литературных данных о роли ретинола как компонента системного метаболизма, влияющего на функционирование репродуктивной системы, рассматриваются последствия его дефицита. Представлен анализ научно-исследовательских работ ФГБНУ «Научный центр проблем здоровья семьи и репродукции человека» по изучению репродуктивного здоровья населения Восточной Сибири за 20-летний период, а также современные литературные данные о взаимосвязи низкого уровня ретинола и репродуктивных нарушений. Проанализированы результаты 2 600 пациентов, в том числе 2 200 с бесплодием и более 400 подростков, русской и бурятской этнических групп из сельской местности и городов Восточной Сибири, а также малых народов Севера - эвенков и тофаларов. Авторами установлено снижение концентрации ретинола в сыворотке крови женщин и мужчин с бесплодием, а также рост сочетанных гормонозависимых заболеваний при пониженном содержании данного витамина у женщин. Обнаружена взаимосвязь между содержанием ретинола, а-токоферола, тиреоидных гормонов и некоторых биоэлементов крови у женщин с бесплодием. В статье представлены также данные об этнических особенностях метаболического статуса, характерных для коренного населения - бурят и тофаларов. Отмечено снижение уровня ретинола у мальчиков-европеоидов с гормональными нарушениями, проживающих в промышленном городе.
Background. Genetic factors cause 30-50 % of cases of male infertility different forms. We have conducted the investigation of the lipid peroxidation and antioxidant protection system components, associated with the biotransformation genes polymorphisms, in men with infertility. Aims: to study parameters of lipid peroxidation and antioxidant defense system associated with polymorphisms of biotransformation genes in infertile Mongoloid men. Materials and methods. The main group included 143 men of reproductive age from Mongoloid population who came to the Public Health Institution "Republican Perinatal Center" in Ulan-Ude with the problem of one year and more infertility after the marriage. Fifty-three almost healthy males with proven fertility were included in the control group. Blood samples of all men were genotyped by glutathione S-transferase (GSTP1, GSTM1, GSTT1) gene family and activity of glutathione system enzymes was determined. Results. In the fertile Mongoloids with non-functional genotype GSTT1(0/0)/GSTM1(0/0) we have established an increase concentration of a-tocopherol in serum, activity of glutathione peroxidase and a decrease in glutathione-S-transferase, as well as a decrease in the concentration of a-tocopherol. In infertile Mongoloids with non-functional GSTT1(0/0)/ GSTM1 (0/0) genotypes, an increase in the tiobarbituric acid reactants, glutathione peroxidase and a decrease in the concentration of a-tocopherol was found in the ejaculate; we also detected a decrease in the concentration of a-tocopherol, the level of oxidized glutathione and glutathione-s-transferase activity. Conclusions. Genetically determined peculiarities of functioning of the xenobiotic biotransformation system make each individual unique with regard to their adaptive capacity - resistance or sensibility to the damaging exo- and endogenous factors.
The indicators of lipid metabolism were analyzed comparatively in 258 adolescent girls and boys representing major ethnic groups of Eastern Siberia: indigenous Tofalars, Evenks and Buryats and alien Europoids (Caucasoids). The adolescent lipid profile in these groups was found to be ethnos-specific. In contemporary Tofalars and Buryats, its indicators are stable, while the overall lipid profile shows an anti-atherogenic trend. By contrast, Evenks and Europoids show an increasing level of cholesterol-containing blood components.
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.
One of the most topical problems in the field of healthcare is to solve the issues of an early diagnosis, timely prevention and effective treatment of cardiovascular diseases, which include arterial hypertension (the AH]. Prevalence of EAH in the pediatric population in Russia amounts to 20 %. Despite the fact that the mechanisms of the disease were studied in detail, metabolic changes that led to its early deve^ment in teenagers were still not entirely clear. In the Clinic of FSBSI Scientific Center for Family Health Problems and Human Reproduction (Irkutsk], clinical and functional examination of 48 male adolescents aged 14-17 years, of which 25 patients with stable arterial hypertension and 23 adolescents without somatic pathology with normal blood pressure, was conducted. Antioxidant status was studied in blood plasma and hemolysate. A comparative analysis of the following indicators was conducted: total antioxidant activity, superoxide dismutase activity, level of retinol and α-tocopherol, glutathione system parameters. Patients with stable arterial hypertension were recorded with level of overall antioxidant activity in blood 29 % higher than the benchmark, decreased superoxide dismutase activity by 11 % and content of а-tocopherol by 44 %. Retinol concentration in teenagers with hypertension was two times higher than the content of this indicator in the control group (р = 0.00]. Decrease in the antioxidant levels was found in adolescents with arterial hypertension that can be the cause of the oxidative stress development.
The aim of this research was to investigate the glutathione system components and their association with polymorphisms GST genes in men with infertility. Materials and Methods: One hundred and sixty Russian men of reproductive age (Caucasians) who came to the public health institution Republican Perinatal Center in Ulan-Ude with an infertility problem of one year and more after marriage were included in the main group. The control group included 104 men with proven fertility. DNA samples were genotyped for polymorphisms in GSTP1, GSTT1 and GSTM1genes and activity of glutathione system enzymes was determined. Results: The most informative genetic and metabolic indicators in Caucasian males with infertility were combinations of the null genotypes GSTT1(*0/*0)+GSTM1(*0/*0) associated with a decrease of GST activity in blood and ejaculate and an increase of GSH and GPO in the blood. Another combination is GSTP1(Ile105Val)+GSTP1(Ala114Val), which is associated with suppression of the blood and ejaculate GPO activity and a decrease in blood concentration of GSH.
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.
The article presents the results of the research of lipid peroxidation (LPO) and activity of components of antioxidant protection (AOP) in men of reproductive age with primary and secondary infertility, living on the territory of Buryatia and have abnormalities in spermogramme. Aim: to study the frequency structure of male infertility, the features of the system lipid peroxidation-antioxidant protection in men with normospermic and pathospermia Buryat and Russian nationality. A retrospective analysis was performed in 562 men of Russian and Buryat nationality, residing in the territory of the Republic of Buryatia. Study groups were as follows: 204 - Buryat, 358 - Russian. In this study we used clinical and laboratory methods and the statistical analysis of the obtained data. Study the contents of products of lipid peroxidation (LPO) and activity of components of the antioxidant protection (AOP) was studied in 113 infertile men (71 Buryat, 42 Russian). Group of infertile men were divided into a group with normospermia and pathospermia. High rate of male factor infertility in men of Russian and Buryat populations was found. No difference was found for frequency and structure of reproductive disorders in men depending on ethnicity. The frequency of male factor in infertile marriages and structure of the causes of male infertility and made comparisons based on ethnicity. Was found the presence of oxidative stress in patients with pathospermia. The findings suggest about the unfavorable pro-and antioxidant status of men with pathospermia, both Russian and Buryat populations. The differences indicate a different degree of activity of metabolic processes in infertile men of different ethnic groups.
The article presents the analysis of inspection results of the military personnel who passed a medical examination at the initial military registration, with the call to military service and recognized as health fit for military service. The aim of the research was to study the dynamics of changes in the components of lipid peroxidation and antioxidant defense system of the soldiers during the primary adaptation to military service. Materials and methods: 34 young men (recruits), called up for military service, and 18 military personnel who have served 6 months. As material for biochemical research we used blood plasma and hemolysate. Modern spectrophotometric, fluorometric and statistical methods have been used. Results. In recruits, we noted increased activity of lipids oxidation, low level of blood antioxidant activity and reduced glutathione. In 6 months of the military service we found decreased contents of TBA-active products and improving of the overall antioxidant activity of the blood. Conclusions. Analysis of the data shows significant changes in the indices of lipid peroxidation and antioxidant defense system. The ratio of the activity of oxidation and antioxidant components not only reflects, but also largely determines the rate of metabolism and adaptive capabilities of the organism. The study found that young people, who were recognized as fit for military service due to health criteria for military medical commissions by military commissioners and were called up for military service, have low adaptive capacity and reach the stage of “satisfactory adaptation” only after 6 months of service.
The research is devoted to studying the features of antioxidant protection system in fertile men of various ethnic groups. Studying the features of antioxidant protection processes in the populations of various ethnic origins, living in identical geographical conditions, is of scientific interest. 126 men of reproductive age (84 men of Russian population and 42 men of Buryat population living in Ulan-Ude) were examined. Blood plasma and hemolysate were used as the material for the biochemical research. Modern spectrophotometric, fluorometric and statistical methods were used. The basic indicators of lipid peroxidation, reflecting different stages of oxidation (рrimary,, intermediate, final products] and total antioxidant activity of blood, which characterizes the total activity of inhibitors of radical oxidation, and determining its buffering capacity were studied. We investigated the basic units of antioxidant protection - enzymatic (superoxide dismutase) and non-enzymatic (low molecular weight soluble vitamins retinol and а-tocopherol, oxidized and reduced glutathione). The peculiarities of Ирid peroxidation and antioxidant protection processes in fertile men have significant differences. They can be attributed to the ethnic origin and characterize various degrees of activity of metabolic processes in the surveyed groups. Studying the condition of antioxidant protection system will significantly expand ideas of organism adaptation opportunities to external conditions and will be able to become a basis for effective monitoring of reproductive health.
Numerous studies indicate the activation of free radical processes in different stages and in different types of diabetes. The impact of ethnic factors on the course of the disease is of particular interest. The aim of this study was investigation of the lipid peroxidation content components in Mongoloids with type 1 diabetes mellitus (T1DM). The study included living in Eastern Siberia Mongoloid patients with T1DM (n = 38, mean age - 34,4 ± 1,9 years, duration of the disease - 12,05 ± 1,51 years). The "T1DM" diagnosis in all patients was confirmed by clinical and laboratory investigations. Severe comorbidities and severe diabetic complications were excluded. The average level of glycated hemoglobin in Mongoloids was 8,65±1.39%. The control group consisted of healthy individuals: Mongoloids with absence of family history for diabetes (n = 34, mean age 30,3 ± 1,3 years). Serum and hemolysate used as material for the study. Spectrophotometric and fluorometric methods used. In Mongoloid patients the diene conjugates level increased compared with the control group has been found (1.34-times higher , p<0,01). Antioxidant status in T1DM Mongoloids was characterized by a statistically significant increased blood total antioxidant activity (1.54-times higher, p<0,001) and a slight decreased superoxide dismutase activity (p<0,01) comparing to control group. Changes in the system of POL-AOD in Mongoloid-patients are characterized by low intensity, which is probably due to the increased activity of the antioxidant defense system. These data are confirmed by clinical course of type 1 diabetes mellitus with a rare development of complications in Mongoloids of Eastern Siberia compared to average performance in all population and figures of European one.
Adolescent girls and women of reproductive age, female representatives of the Evenk ethnos and Europeoids that co-inhabit the north of the Irkutsk oblast, were examined. Changes in metabolic reactions in the small indigenous ethnic group were found to have a more adaptive character than in the Europeoids. In the Evenk vs. Europeoid girls, an increased activity both of glucocorticoid function of the adrenal glands and non-enzymatic antioxidant defense system was detected. In spite of the higher total cholesterol (TCh) level in women vs. girls in both ethnic groups, in the Evenk group TCh tended to decline. Changes in the antioxidant defense system of the Evenk women manifested themselves as an increased total antioxidant activity of blood vs. Europeoids as well as higher TCh and lower retinol levels vs. adolescent girls.
Among main tasks of andrology, besides search of new pharmaceuticals, an important place takes the profound analysis of pathogenesis of formation of infertility in males in every particular case with purpose of selection of pathogenetically justified therapy. The article presents the results of application of glucocorticoid medications for normalization of indices of spermogram in males with reproduction disorders. Two age groups were examined. The first group consisted of 45 individuals of 21-35 years and the second group included 30 individuals of 36-45 years. All males were applied standard clinical laboratory analysis examination including andrologist's examination, ltrasound examination of organs of scrotum and prostate, macro- and microscopic analysis of ejaculate, hormonal analysis. The treatment of patients consisted of application of medication of glucocorticoid hormones - Dexamethasonum with dosage depending on expression of hormonal alterations (0.25 mg - 1.5 mg per day). In males with supra-renal hyper-androgeny application of glucocorticoid hormones demonstrated higher efficiency of hormone therapy for correction of the given condition at absence of any side-effects that permitted to ameliorate reproductive function by normalizing indices of spermatogenesis and level of supra-renal hormones. At the given mode of treatment of pathozoospermia in males with supra-renal hyper-androgeny occurs increasing of concentration of active spermatozoa participating in fertilization and also terms of vitality of spermatozoa and activity of spermatogenesis. It is established that similar treatment shows no side-effects on organism and it has no significant contraindications for application.
AIMTo investigate the quality of sperm, total antioxidant activity, concentrations of -tocopherol and lipid peroxidation in men of reproductive age living in Ulan-Ude, Irkutsk, and Novosibirsk.MATERIALS AND METHODSThe analysis of sperm quality included measuring the volume and pH of the ejaculate, sperm cell count, the proportion of motile sperm cells of A and B categories.RESULTSHealthy men living in Irkutsk were found to have 34.4 and 23.6% higher sperm count (millions per ml) compared to men living in the city of Novosibirsk and Ulan-Ude, respectively. They also had a 44 and 38% statistically significantly greater concentration of alpha-tocopherol than men living in Ulan-Ude and Novosibirsk, respectively. Men from Ulan-Ude had 16 and 11% greater counts of active spermatozoa than men from Novosibirsk, respectively, and 34 and 13% higher levels of total antioxidant activity of ejaculate, respectively.CONCLUSIONThe findings on quality of the ejaculate and features of lipid peroxidation in men living in various Siberian cities show that the place of residence and ecological and geographical location affect functioning of the reproductive system and the heterogeneity of male infertility under anthropogenic pressure.
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.