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Androgens are required for stimulation and maintenance of skeletal growth and bone homeostasis. Physiological functions of androgens are mediated through the androgen receptor (AR). The androgen receptor gene AR has a polymorphic trinucleotide CAG repeat and the length of AR CAG repeats determining the sensitivity of bone tissue to androgens is associated with skeleton formation and body proportions. This study aimed to investigate the relationship between AR CAG repeat polymorphism, circulating sex steroid hormones and the anthropometrics in males of different ethnic origins. Male volunteers of three ethnic groups (Slavs, Buryats, Yakuts) from urban Russian populations were recruited in a population-based study (n = 1078). Anthropometric indicators (height, arm span, leg length, the length of 2 and 4 digits of both hands) were measured and the following anthropometric indices were calculated: the ratio of height to leg length, the ratio of arm span to height, the ratio of lengths of second to fourth digit of the hand. Serum testosterone and estradiol were determined by enzyme immunoassay. Genotyping of the AR CAG repeats was performed using fragment analysis and capillary electrophoresis. Ethnic differences in all anthropometric and hormonal indicators have been established, with higher anthropometric indicators in Slavs than Buryats, and in most cases higher than in Yakuts. The testosterone level was higher among Slavs compared to Buryats, but did not differ from Yakuts; the estradiol level was lower among Slavs compared to Buryats, who did not differ from Yakuts. Buryats and Yakuts had a higher number of CAG repeats than Slavs (medians: Slavs, 23; Buryats, 24; Yakuts, 25). Positive correlations were found between the length of AR CAG repeats and estradiol levels in Buryats and testosterone levels in Yakuts, while longer CAG repeats were accompanied by higher estradiol levels in Buryats and testosterone levels in Slavs and Yakuts. Ethnic-specific correlations have been established between the steroid hormone levels and some anthropometric indicators in all ethnic groups. Available data suggest that the ethnic-specific associations of AR CAG repeats with anthropometrics can be mediated by sex steroid hormones as important regulators of skeletal growth and bone homeostasis., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

We evaluated possible associations of overweight and obesity with semen parameters, sperm DNA fragmentation (SDF), and different indicators of metabolic and hormonal status in young men (n=226, mean age 22.5 years). Overweight and obese men were found to have a significant deterioration of metabolic health, reduced total sperm count and concentration, serum testosterone, and inhibin B levels, and increased serum leptin and seminal zinc levels in comparison with men with normal weight, although sperm DNA fragmentation, motility, and morphology did not change. In overweight and obese men, increased seminal zinc content appears to perform a protective function via reduction of oxidative stress caused by excess body fat. It is assumed that in the absence of individual lifestyle correction and weight loss for a long time, obese subjects are not protected from the development of reproductive comorbidities, in particular, subfertility and infertility., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study was to find out whether the seminal testosterone and/or estradiol levels could serve as prognostic criteria for normal spermatogenesis and whether they are able to characterize the sperm pathology. The study involved healthy young male volunteers (n=269); serum and seminal steroid hormones were measured; the sperm concentration, mobility, and morphology were evaluated. The results indicate that the seminal testosterone concentration is lower (p<0.05) and the seminal estradiol is higher than the corresponding parameters in the serum (p<0.05). The seminal testosterone and estradiol concentrations negatively correlated with the sperm concentration, and the seminal estradiol concentration was higher in pathozoospermic than in normospermic men (p<0.05). It is assumed that the seminal estradiol level can be an indicator of sperm quality and serve as a biological predictor of normal spermatogenesis; in addition, this parameter can be used for diagnostic purposes in patients with impaired spermatogenesis induced by excess of estrogens., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Trace elements are important factors in human health. Zinc, an essential trace element, is necessary for normal functioning of many body systems where it plays an important role in metabolism. Obesity is accompanied by various metabolic pathologies provoking the development of dyslipidaemia, metabolic syndrome, type 2 diabetes mellitus, arterial hypertension, cardiovascular diseases and cancer. Many studies demonstrate changes in zinc homeostasis in obese men, but the data are conflicting, and a relationship between serum zinc and anthropometric and metabolic indicators remains controversial. In this study we have investigate the relationship between serum zinc level and body mass index (BMI), waist circumference (WC), and some metabolic parameters in Russian men. In 260 young men from the general population (n=268, median age 22 years), serum zinc, triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL and LDL), glucose and uric acid levels were determined, as well as body weight, height, waist circumference (WC), and BMI were evaluated. According to BMI, men were divided into four groups: deficient and normal body weight, overweight, obesity. According to WC men were subdivided into two groups: normal and abdominal-visceral type of obesity. The median serum zinc concentration in men of the entire studied population was 20.3 μmol/l, and in men with obesity (BMI≥30) the median serum zinc concentration was higher than in the corresponding value in men with normal weight (30.9 and 20.8 μmol/l, respectively, p<0.01). Serum levels of TG, TC and LDL in obese men were also significantly higher (p<0.01) as compared to men with normal weight. In men with abdominal-visceral obesity, the median serum zinc concentration was significantly higher in comparison with control (26.3 and 19.9 μmol/l, respectively, p<0.01). It is suggested that elevated serum zinc level in obese young men can counter chronic inflammation and oxidative stress caused by increased body fat.

One of the greatest achievements of genetics in the 20th century is D.K. Belyaev's discovery of destabilizing selection during the domestication of animals and that this selection affects only gene expression regulation (not gene structure) and inf luences systems of neuroendocrine control of ontogenesis in a stressful environment. Among the experimental data generalized by Belyaev's discovery, there are also f indings about accelerated extinc tion of testes' hormonal function and disrupted seasonality of reproduction of domesticated foxes in comparison with their wild congeners. To date, Belyaev's discovery has already been repeatedly conf irmed, for example, by independent observations during deer domestication, during the use of rats as laboratory animals, after the reintroduction of endangered species such as Przewalski's horse, and during the creation of a Siberian reserve population of the Siberian grouse when it had reached an endangered status in natural habitats. A genome-wide comparison among humans, several domestic animals, and some of their wild congeners has given rise to the concept of self-domestication syndrome, which includes autism spectrum disorders. In our previous study, we created a bioinformatic model of human self-domestication syndrome using differentially expressed genes (DEGs; of domestic animals versus their wild congeners) orthologous to the human genes (mainly, nervous-system genes) whose changes in expression affect reproductive potential, i. e., growth of the number of humans in the absence of restrictions caused by limiting factors. Here, we applied this model to 68 human genes whose changes in expression alter the reproductive health of women and men and to 3080 DEGs of domestic versus wild animals. As a result, in domestic animals, we identif ied 16 and 4 DEGs, the expression changes of which are codirected with changes in the expression of the human orthologous genes decreasing and increasing human reproductive potential, respectively. The wild animals had 9 and 11 such DEGs, respectively. This difference between domestic and wild animals was signif icant according to Pearson's χ2 test (p < 0.05) and Fisher's exact test (p < 0.05). We discuss the results from the standpoint of restoration of endangered animal species whose natural habitats are subject to an anthropogenic impact., (Copyright © AUTHORS.)

Trace elements play an important role in human health. They are involved in growth, development, reproduction, and other physiological functions. Among them, special attention is paid to zinc, which is an essential trace element required for the normal functioning of many organ systems. Experimental data have been accumulated indicating a significant role of zinc in the functioning of the male reproductive system and the spermatogenesis. Zinc concentration in seminal plasma is considerably higher compared to those in other body fluids. In contrast to its serum concentration, seminal zinc level is associated with the sperm concentration, motility and morphology. Under dietary deficiency, Zinc supplementation can significantly increase the ejaculate volume, sperm motility and morphology and improves overall sperm quality in infertile patients. Zinc, being a structural element of a large number of different macromolecules and enzymes, shows antioxidant, antibacterial and antiapoptotic properties in the testes. It should be considered as one of the trace elements with great potential for the prevention and treatment of male infertility and subfertility. The aim of this review is to analyze current publications and summarize information about the effect of zinc on male fertility and its properties related to sperm quality and successful fertilization.

Genetic causes of the global decline in male fertility are among the hot spots of scientific research in reproductive genetics. The most common way to evaluate male fertility in clinical trials is to determine semen quality. Lower semen quality is very often accompanied by subfertility or infertility, occurs in many diseases and can be caused by many factors, including genetic ones. The following forms of lowered semen quality (pathozoospermia) are known: azoospermia, oligozoospermia, asthenozoospermia, teratozoospermia, and some combined forms. To systematize information about the genetic basis of impaired spermatogenesis, we created a catalog of human genes associated with lowered semen quality (HGAPat) and analyzed their functional characteristics. The catalog comprises data on 126 human genes. Each entry of the catalog describes an association between an allelic variant of the gene and a particular form of lowered semen quality, extracted from the experimental study. Most genes included into the catalog are located on autosomes and are associated with such pathologies as non-obstructive azoospermia, oligozoospermia or asthenozoospermia. Slightly less than half of the included genes (43%) are expressed in the testes in a tissue-specific manner. Functional annotation of genes from the catalog showed that spermatogenic failure can be associated with mutations in genes that control biological processes essential for spermiogenesis (regulating DNA metabolism, cell division, formation of cellular structures, which provide cell movement) as well as with mutations in genes that control cellular responses to unfavorable conditions (stress factors, including oxidative stress and exposure to toxins)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ignatieva, Osadchuk, Kleshchev, Bogomolov and Osadchuk.)

Reproductive potential is the most important conditional indicator reflecting the ability of individuals in a population to reproduce, survive and develop under optimal environmental conditions. As for humans, the concept of reproductive potential can include the level of the individual's mental and physical state, which allows them to reproduce healthy offspring when they reach social and physical maturity. Female reproductive potential has been investigated in great detail, whereas the male reproductive potential (MRP) has not received the equal amount of attention as yet. Therefore, here we focused on the human Y chromosome and found candidate single-nucleotide polymorphism (SNP) markers of MRP. With our development named Web-service SNP&#95;TATA&#95;Z-tester, we examined in silico all 35 unannotated SNPs within 70-bp proximal promoters of the three Y-linked genes, CDY2A, SHOX and ZFY, which represent all types of human Y-chromosome genes, namely: unique, pseudo-autosomal, and human X-chromosome gene paralogs, respectively. As a result, we found 11 candidate SNP markers for MRP, which can significantly alter the TATA-binding protein (TBP) binding affinity for promoters of these genes. First of all, we selectively verified in vitro the values of the TBP-promoter affinity under this study, Pearson's linear correlation between predicted and measured values of which were r = 0.94 (significance p < 0.005). Next, as a discussion, using keyword search tools of the PubMed database, we found clinically proven physiological markers of human pathologies, which correspond to a change in the expression of the genes carrying the candidate SNP markers predicted here. These were markers for spermatogenesis disorders (ZFY: rs1388535808 and rs996955491), for male maturation arrest (CDY2A: rs200670724) as well as for disproportionate short stature at Madelung deformity (e. g., SHOX: rs1452787381) and even for embryogenesis disorders (e. g., SHOX: rs28378830). This indicates a wide range of MRI indicators, alterations in which should be expected in the case of SNPs in the promoters of the human Y-chromosome genes and which can go far beyond changes in male fertility., (Copyright © AUTHORS.)

Currently, the global demographic crisis in industrialized countries, including Russia, is accompanied by a decrease in the reproductive potential of human populations. In different regions of the world, a decrease in male fertility has been observed that expressing in poor semen quality, increasing in the proportion of male factor in infertile couples and the growth of congenital anomalies of the male reproductive system, resulting to infertility. The observed negative trends in a range of male reproductive problems highlighted the global problem of maintaining mens health, as well as raised the question of the causes of this phenomenon. Taking into account the increasing risks associated with reproduction of humanity, epidemiological studies of male fertility have been started in various countries of the world. The purpose of this review is to analyse epidemiological studies of male fertility, regional and ethnic differences in biological indicators of male fertility. The review provides information on regional and ethnic differences in male fertility in Western Europe, the United States, China, Japan and other countries. Based on our review of epidemiological data we can conclude that the region of residence and ethnicity are important determinants of the male reproductive potential, which can have a significant impact on its variability. Traditional methods of population studies of male fertility are considered, based on which time trends, regional and ethnic differences in the male reproductive potential are studied, and adequate information about the prevalence and causes of male infertility and subfertility can be obtained.

Background: The progress of medicine, science, technology, education, and culture improves, year by year, quality of life and life expectancy of the populace. The modern human has a chance to further improve the quality and duration of his/her life and the lives of his/her loved ones by bringing their lifestyle in line with their sequenced individual genomes. With this in mind, one of genome-based developments at the junction of personalized medicine and bioinformatics will be considered in this work, where we used two Web services: (i) SNP&#95;TATA&#95;Comparator to search for alleles with a single nucleotide polymorphism (SNP) that alters the affinity of TATA-binding protein (TBP) for the TATA boxes of human gene promoters and (ii) PubMed to look for retrospective clinical reviews on changes in physiological indicators of reproductive potential in carriers of these alleles., Results: A total of 126 SNP markers of female reproductive potential, capable of altering the affinity of TBP for gene promoters, were found using the two above-mentioned Web services. For example, 10 candidate SNP markers of thrombosis (e.g., rs563763767) can cause overproduction of coagulation inducers. In pregnant women, Hughes syndrome provokes thrombosis with a fatal outcome although this syndrome can be diagnosed and eliminated even at the earliest stages of its development. Thus, in women carrying any of the above SNPs, preventive treatment of this syndrome before a planned pregnancy can reduce the risk of death. Similarly, seven SNP markers predicted here (e.g., rs774688955) can elevate the risk of myocardial infarction. In line with Bowles' lifespan theory, women carrying any of these SNPs may modify their lifestyle to improve their longevity if they can take under advisement that risks of myocardial infarction increase with age of the mother, total number of pregnancies, in multiple pregnancies, pregnancies under the age of 20, hypertension, preeclampsia, menstrual cycle irregularity, and in women smokers., Conclusions: According to Bowles' lifespan theory-which links reproductive potential, quality of life, and life expectancy-the above information was compiled for those who would like to reduce risks of diseases corresponding to alleles in own sequenced genomes. Candidate SNP markers can focus the clinical analysis of unannotated SNPs, after which they may become useful for people who would like to bring their lifestyle in line with their sequenced individual genomes.

Introduction: Smoking and alcohol consumption remain widespread throughout the world, including Russia. Recently, due to the increase in male infertility and subfertility, special attention has been paid to the effects of smoking and alcohol on the reproductive health of young men. The aim of this study was to assess the effects of smoking and moderate alcohol consumption on spermatogenesis, reproductive hormone levels and metabolic status in young men living in Western Siberia (Novosibirsk)., Materials and Methods: One hundred thirty-three volunteers (mean age 21.1+/-0.3 years) were tested for the sperm concentration, the proportion of mobile and morphologically normal spermatozoa in the ejaculate, blood serum levels of follicle-stimulating and luteinizing hormones, prolactin, testosterone, estradiol, inhibin B, triglycerides, total cholesterol, high and low density lipoprotein cholesterol, glucose and uric acid., Results: and conclusions The studied lifestyle factors were found to have no effects on spermatogenesis. Smoking more than 10 cigarettes per day and a moderate frequency of alcohol consumption (up to 1 time per week) was associated with higher blood serum testosterone levels and engaging in more frequent sexual contacts compared to non-smoking and non-drinking men. Drinking alcohol more than once a week and smoking more than 8 cigarettes per day was associated, along with the increase in testosterone levels and the frequency of sexual contacts, with lower levels of follicle-stimulating hormone and higher serum triglyceride levels. Thus, in young men, frequent drinking and smoking can alter the hormonal and metabolic balance, which, as the duration of the exposure and the strength of the factors increase, will increase the risk of reproductive disorders.

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 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.

The objective of the present study was to evaluate sperm quality and reproductive hormonal level in an unselected population of men who were permanent residents of the Yakutsk city and compare the semen and hormonal parameters with the World Health Organization (WHO, 2001) recommended normal values and the results from other countries. A total of 145 men (mean age 24 years) agreed to be included in the study. All the volunteers completed a questionnaire, received a general and reproductive health examination by an andrologist, gave semen and blood samples. There are no differences between Yakut and Slavs in anthropometric, hormonal or sperm measures, but height and ejaculate volume were higher in Slavs than Yakut men. The data obtained indicated high frequency of suboptimal quality of sperm in males of both nations from this Siberian region in comparison with other Russian regions or European countries.

The objective of the present study was to evaluate sperm quality and reproductive hormonal level in an unselected population of men who were permanent residents of the Yakutsk city and compare the semen and hormonal parameters with the World Health Organization (WHO, 2001) recommended normal values and the results from other countries. A total of 145 men (mean age 24,1 years) agreed to be included in the study. All the volunteers completed a questionnaire, received a general and reproductive health examination by an andrologist, gave semen and blood samples. We found that the means were 34,69 - 106 spermatozoa/mL for sperm concentration and 39,6% for total motile spermatozoa. Among all volunteers studied 4,3% had azoospermia, 27,0% reported oligozoospermia, 68,1% - asthenozoospermia. There are no differences between Yakut and Slavs in anthropometric, hormonal or sperm measures, but height and ejaculate volume were higher in Slavs than Yakut men. The data obtained indicated high frequency of suboptimal quality of sperm in males of both nations from this Siberian region in comparison with other Russian regions or European countries.

Strain-specific differences in the production of spermatozoa and incidence of atypical spermatogenesis were studied in males of 7 inbred strains: BALB/cLac, PT, CBA/Lac, DD, A/He, C57Bl/6J, and YT. The results attest to significant genetic variability of the counts of epididymal spermatozoa (differing by more than 1.5-2 times) and incidence of abnormal spermatozoon heads (differing by more than 4 times). However, the strain-specific variability of both signs was not coordinated. The selected set of inbred mouse strains can become a prospective genetic model for studies of physiological and hereditary nature of spermatogenesis variability.

The study was designed to investigate genetic differences in reproductive consequences of social hierarchy using inbred mice strains BALB/cLac, PT and CBA/Lac. Two adult males of different genotypes were housed together for 5 days. Hierarchical status of both partners was determined by asymmetry in agonistic behavior. The number of epididymal sperm and a proportion of abnormal sperm, weights of reproductive organs, serum concentration and testicular content of testosterone, and the testosterone response to introduction of a receptive female were determined. The testosterone measures were significantly decreased in the PT strain, the epididymal sperm number was significantly decreased in the BALB/cLac strain and a proportion of abnormal sperm heads was significantly increase in the CBA/Lac (in both dominants and subordinates) as compared to control mice. The testicular testosterone response to a receptive female and precopulatory behavior was unchanged in dominants and suppressed in subordinates of the BALB/cLac strain. The results indicate that in laboratory mice the pattern of reproductive response to social hierarchy is determined by genetic background.

The aim of present study was to reveal the genetic effects on social dominance and patterns of agonistic behaviors in social partners. The study was carried out in adult male mice of three inbred strains BALB/cLac, CBA/Lac and PT using an ethological model of social hierarchy, which is characterised by the minimal size and genetic heterogeneity (two males of different genotypes). We used a neutral territory as the experimental territorial condition for the establishment of social hierarchy. Rank asymmetry in aggressive and defensive behaviors was quickly formed during the first day after the production of the social. Significant interstrain differences in time patterns ofagonistic behavior in dominants and subordinates as well as in the level of social dominance determined as a proportion of dominant animals in the strain were observed. In was shown that, in laboratory mice, the genotype could markedly influence social dominance and the patterns of agonistic behavior in social partners.

Sexual behaviour and testosterone output in response to a receptive female were investigated in male mice of three inbred strains BALB/cLac, CBA/Lac and PT at puberty (45 days of age) and in adulthood (90 days of age). The animals were exposed for 10 min to a receptive female separated by a plastic grill, which would not allow contact between male and female. Male and female behaviour was recorded by measuring the time the male or female spent at the grill and the number of approaches to it (sexual motivation). The grill was then removed and the number of mounts and chemoinvestigatory behavior towards a female (nasal and anogenital sniffing) was recorded for each male. An increase in serum concentration and testicular content of testosterone was used as an endocrine index of the sensitivity to female pheromones. It has been shown the significant genotype and developmental effects on sexual behaviour and the hormonal response to sexual stimuli. The pubertal BALB/cLac males were characterised by the adult pattern of sexual motivation, chemoinvestigatory behaviour and the evident testosterone respond to a female. Males of the strain PT showed the lowest sexual motivation, chemoinvestigatory behavior towards a receptive female and no testosterone responses at both ages. This is a very different situation with the CBA/Lac's who showed the developmental increase in the sexual motivation, sniffing behaviour and the endocrine reflex, and the highest level of sexual behaviour but the moderate testosterone respond to a female at adulthood. The data obtained suggest genotype related asynchrony in maturation of the olfactory system, pituitary-gonadal axis and neural circuits of sexual behavior, and their independent genetic control. So, the set of mice strains investigated represents a useful tool for genetic and endocrine study of sexual behavior and the chemosensory control of testicular steroidogenesis.

In laboratory male mice the effects of social hierarchy on hormonal and spermatogenic testicular function, accessory organs and testicular weights, sexual behaviour have been investigated using an experimental model of social hierarchy, which is characterised by a minimal size (two male mice) and 5 days period of social interactions. The social rank of the partners was detected by asymmetry in aggressive behaviour. Using the experimental condition, when the both partners have no preferences for exclusive use of area we demonstrated that there were no rank differences in the number of mounts and testicular testosterone content. Nevertheless a rank asymmetry in the male sniffing behaviour towards a receptive female, weights of the testes, seminal vesicles, epididymes and the number of epididymal sperm was kept up in a stable social group. Social dominance was found to affect negatively on testicular testosterone increase in response to introduction of a receptive female and sexual attractiveness of male to a receptive female in both dominant and subordinate males. The results obtained demonstrate the impact of social hierarchy on reproduction in laboratory male mice, particular in respect of spermatogenesis and the testicular testosterone in response to a receptive female.

Asymmetry of social rank in the competition for food and female was studied using the social dominance model with only two male mice. Marking activity was recorded as a useful indicator of the social status. Social rank was determined by asymmetry in aggressive behavior. A food test was presented for 10 min daily within 5 days of the experiment, whereas a sexual test was performed only on the 5th day for 30 min. Marking behavior was estimated twice: before the first interaction and on the 4th day of the experiment. The competition for food was accompanied by active attacks, escapes, vertical defense postures, and sniffing. The level of aggression, sniffing, and food activity was higher in dominant than submissive males. Time course of aggressive, defensive, and sniffing behaviors was characterized by maximum scores in the period of formation of social hierarchy; however, the rate of food activity in this period was low and increased only to the 4th day. Introduction of a receptive female into the male group with the stable social hierarchy stimulated the intermale aggression, defensive and sniffing behaviors. Dominant males were characterized by a greater number of victories over and sniffing contacts with both male and female. Marking activity was also more intense in dominants. Thus, significant unidirectional rank differences in agonistic, sniffing, food, sexual, and marking behaviors were shown on the social dominance model with the minimum number of partners.

The goal of the investigation is to establish a new experimental model of social hierarchy in laboratory mice. The important feature of the model is a group of two males only placed into the special experimental cage. The cage consists of two nestling chambers and central chamber. Observations were made 3 times per day (20 min each) throughout 5 days. Aggression, defence and sniffing behaviours of both partners were recorded during each observation period using video camera. Social rank was detected by asymmetry in aggressive behaviour. It was shown that social hierarchy was established during the first four tests limited by the first 24 h after pairing. After this period aggression and defence behaviours were greatly decreased. After the first 5 tests a stabilization in aggression (number of wins, active attacks and not direct aggression) and defence (number of vertical defensive postures and escapes) as well as sniffing behaviours took place. But a strong asymmetry in mentioned here behaviours in males of different ranks (dominants and subordinates) was kept up. Thus we offer a new experimental model of minimal society, which entirely reproduces a pattern of establishment and maintenance of social hierarchy. Our model demonstrates significant differences in agonistic, defence and sniffing behaviours between males of different social rank.

Using gel retardation of DNA samples and specific antibodies, binding sites for the transcription factor SF-1 were found in positions -53/-44 and -285/-270 in the promoter region of the mouse Cyp17 gene and in position -117/-108 of the promoter region of the mouse 3betaHSDI gene.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

This white paper by eighty members of the Complex Trait Consortium presents a community's view on the approaches and statistical analyses that are needed for the identification of genetic loci that determine quantitative traits. Quantitative trait loci (QTLs) can be identified in several ways, but is there a definitive test of whether a candidate locus actually corresponds to a specific QTL?

Using 42 nucleotide sequences extracted from the Transcription Regulatory Regions Database (TRRD) containing SF-1 transcription factor binding site, we have determined the decanucleotide (GTCAAGGTCA) consensus sequence for SF-1 binding. In the frequency matrix of this sequence nucleotides between the 3rd and the 7th position had the highest frequency and guanine nucleotides at the 6th and the 7th positions were recognized in all nucleotide sequences. The latter suggests a crucial role of these guanines for the interaction of DNA with SF-1 protein. The determined consensus and frequency matrix were used for search of putative SF-1 binding sites in regulatory regions of two genes, encoding mouse Cyp17 (17alpha-hydroxylase/17-20-lyase) and 3betaHSDI (3beta-hydroxysteroid dehydrogenase/4delta-5delta-isomerase I), the microsomal enzymes involved in steroidogenesis. 5;-Flanking regions of genes encoding Cyp17 and 3betaHSDI were shown to contain six and five such binding sites, respectively. The presence of the putative SF-1 binding sites in the regulatory regions of mouse Cyp17 and 3betaHSDI suggests that gene SF-1 could represent one of the putative genes which (as we predicted earlier) determine coordinated inheritable variability of hormonal activity in mouse Leydig cells.

Changes in in vitro testosterone production by Leydig cells induced by chorionic gonadotropin, dibutyryl-cAMP, and pregnenolone have been studied during postnatal development of four inbred mouse strains BALB/c, PT, CBA/Lac, and A/He, with contrast hormonal activity of testes in sexually mature males. The interlinear differences significantly change with age of the males by all studied indices indicating genotype-dependent formation of hormonal activity of Leydig cells during postnatal development. Coordinated interlinear variability between all indices of Leydig cells reactivity has been established for each studied period of postnatal development. Hence, we have established coordinated interlinear genetic variability of hormonal function of Leydig cells, which was confirmed by considerable changes in it during postnatal development at puberty. Definitive genotypic differences in hormonal activity of Leydig cells appeared by late pubertal and early postpubertal development (day 60) and coincided with termination of morphological differentiation of Leydig cells and appearance of the differentiated cell population.

Production of testosterone by Leydig cells during the postnatal ontogeny in pubescence under in vitro stimulation by chorionic gonadotropin, dibutiryl-cAMP, and pregnenolon was studied in males of four inbred mouse lines (BALB/c, RT, CBA/Lac, and A/He) and their F1 reciprocal hybrids. Highly statistically significant association between the animal genotype and age was revealed for all parameters studied, which indicates the genotype-dependent formation of the Leydig cell hormone function during the postnatal ontogeny. The effect of genotype was characterized by two specific features. First, in each postnatal ontogeny stages examined correlative genetic variability in respect of the cAMP- and substrate-dependent indices of Leydig cell reactivity was observed. Second, during postnatal ontogeny coordinated genetic variability was subjected to substantial ontogenetic rearrangements. Definite pattern of genetic differences in the Leydig cell hormone activity was formed only at the late pubertal--early post- pubertal stage (60th day after birth). This process coincided with the completion of the Leydig cell morphological differentiation and the appearance of mature cells in the population. Thus, formation of the Leydig cell hormone activity during postnatal ontogeny is under coordinated genetic control, which is also subjected to substantial changes during pubertal differentiation.

Several steps of cAMP- and substrate-dependent testosterone production in the testes were studied with laboratory mouse micropopulations of six inbred strains (A/He, CBA/Lac, C57BL/6J, DD, YT, PT). The strains differed in basal testosterone production in the gonads and in its response to activation of the adenylate cyclase signal transduction pathway at various steps by human chorionic gonadotropin (hCG), the cholera toxin, forskolin, and dibutyryl-cAMP and in the presence of pregnenolone, an early precursor of testosterone. Establishment of dominant-subordinate relationships in mouse populations substantially affected testosterone production in response to all activators of testicular steroidogenesis. The secretory activity of the testes decreased at the early establishment of social hierarchy in experimental micropopulations, then returned to the initial level, and again decreased in the case of activation with hCG, dibutyryl-cAMP, and pregnenolone. With all activators of steroidogenesis, basal and activated testosterone production changed in the same direction during the establishment and maintenance of social hierarchy, suggesting coordinated changes in all examined steps of testosterone biosynthesis in the testes. The among-strain differences in response to all activators of steroidogenesis remained much the same at various stages of the establishment of social hierarchy. The parameters of cAMP- and substrate-dependent testosterone production averaged over individual stages of the establishment of social hierarchy proved associated. Their genotypic correlations were positive and, in many cases, significant. Subsequent component analysis showed that one principal component accounted for more than 80% of the total among-strain variation, suggesting a coordinated genetic control of the endocrine function of the testes.

Micropopulations consisting of six male mice of different genotypes were studied (each of lines A/He, CBA/Lac, C57BL/6J, DD, YT, and PT was represented by one male). Interlinear differences in the level of social dominance and the effects of genotype, social hierarchy, and season on in vitro testosterone production by testes were examined under different incubation conditions. The testosterone production was estimated under control conditions and under stimulation with human chorionic gonadotropin (CG). Significant genetic differences in the initial and CG-stimulated testosterone production by testes incubated in vitro were found. By the control production, the genotypes fell into two groups: lines C57BL/6J, A/He, and CBA/Lac had low production of the hormone; lines YT, PT, and DD, high production. By responsiveness of gonads to CG, the genotypes fell into three groups: line CBA/Lac had low testosterone production by testes; lines C57BL/6J, A/He, YT, and DD, line PT, intermediate production; and line PT, high production. The obtained data indicate stability of genetic polymorphism for the responsiveness of testes to gonadotropins, because neither season nor the formation of social hierarchy could significantly change the interlinear differences. In line PT characterized by high hormonal activity of gonads in the control and under stimulation with gonadotropins, males became dominant in a significantly greater number of cases studied during the formation of hierarchy in micropopulations. The dynamics of both control production of a male sex hormone and responsiveness of testes to CG was established in vitro during the formation of social hierarchy; the effects of season on this dynamics were revealed. Specific characteristics of secretory activity of testes were detected in the control and under stimulation with gonadotropins, depending on incubation conditions. Seasonal and genotypic characteristics of the responsiveness of testes to CG were revealed under different incubation conditions. Genotypic characteristics indicate interlinear differences in the degree of inertia of testosterone biosynthesis on exposure to gonadotropins.

Four activities of key microsomal steroidogenic enzymes (3 beta-hydroxysteroid dehydrogenase-isomerase, microsomal cytochrome P45017 beta, and 17-ketosteroid reductase) were compared in Leydig cells of six inbred strains of mice: A/He, CBA/Lac, C57BL/6J, DD, YT, and PT. The activities of the enzymes were found to vary considerably from one strain to another, depending on the genotype. Analysis of testosterone biosynthesis revealed a decreased activity of 17-ketosteroid reductase as compared to the activities of other microsomal steroidogenic enzymes. The metabolism of pregnenolone and progesterone demonstrated features dependent on the genotype and caused by genotypic differences in the activities of microsomal steroidogenic enzymes. These activities demonstrated a correlative interstrain variation indicative of their coordinated genetic control. The correlative variation may be related to a major gene effect on the activities of microsomal steroidogenic enzymes.

A very effective procedure was developed for separation of sex hormones of the delta 4 pathway using the microcolumn technique of high performance liquid chromatography (HPLC). A five-step gradient containing methanol, acetonitrile and water was used as a mobile phase, while Lychrosorb RP-18 with particles of 5 microns was used as a sorbent. Metabolism of steroid hormones and activity of 3 beta-steroid dehydrogenase, 17 alpha-hydroxylase, C17-20-lyase and 17-ketosteroid reductase were studied in Leydig cells of two mouse strains PT and A/He. The higher rate of steroid metabolism and of the enzymatic activity was detected in the mouse cells of PT strain as compared with those of A/He strain.

A study was made of the role of the adrenergic processes in the activation of the testes endocrine function in male mice of CBA/Lac and A/He strains after their sexual arousal induced by the presence of a sexually receptive female without any tactile contact with a male. The alpha-adrenoceptor blocker phentolamine and the alpha 1-adrenoceptor antagonist prazosin inhibited an increase of testosterone level in the peripheral blood plasma caused by the presence of a female. In contrast, antagonist of the beta-adrenoceptor propranolol and beta 2-adrenoceptor blocker ICI-118.551 significantly intensified the stimulating effect of the female presence on plasma testosterone level. The expression of effects of the adrenoceptor antagonists on the plasma testosterone level depended on a male genotype. At the same time, pretreatment of males with yohimbine, an antagonist of the alpha 2-adrenoceptors, or with metoprolol, a beta 1-adrenoceptor blocker, did not influence the activating effect of a female on the plasma level of testosterone. A conclusion was drawn that during sexual arousal in male mice caused by the presence of a receptive female, the stimulatory effects on the hypothalamic-pituitary-testicular complex were produced through the alpha 1-adrenoceptors, and the inhibitory effects were realized through the beta 2-adrenoceptors.

Levels of adrenaline and noradrenaline were changed in the adrenal glands of 6 male mice genotypes during both the period of intense intermale relationships and the period of absence of fights among the males. The character of the catecholamines changes depended on the animal genotype. Significant interlinear correlations were found among the amounts of adrenaline, noradrenaline and dopamine.

We have studied the role of the adrenergic and dopaminergic mechanisms in the activation of the endocrine testicular function of CBA/Lac and A/He male mice induced by the presence of a female in estrus without any tactile contact with a male. The alpha-adrenoreceptor blocker phentolamine inhibited an increase in the peripheral blood plasma testosterone level caused by the receptive female challenge. Propranolol blockade of beta-adrenoreceptors abruptly increased the stimulating effect of the receptive female presence on the blood testosterone level. The expression of the adrenoblocker action on the blood male sex hormone level depended on a male genotype. The dopamine receptor blocker pimozide produced a moderate effect on the blood testosterone but an attempt to separate its influence into the male sex hormone tonic secretion and the blood testosterone level against a background of sexual activation failed. It was concluded that the adrenergic mechanisms were involved in the activation of the hypothalamo-hypophyseotesticular complex induced by the presence of the receptive female.

Comparative genetic study of the basal plasma testosterone level, relative weights of testicles, seminal vesicles, and preputial glands in 13 strains of laboratory mice showed significant interstrain differences in all indices studied. Under the relative rest condition, a significant positive interstrain (genotypic) correlation was found between basal blood testosterone level and the weight of preputial glands and testicles. At the same time, no intrastrain (paratypic) correlations between hormonal and morphometric indices under study were found. An important positive and highly significant paratypic correlative dependence was seen between the relative weights of seminal vesicles and preputial glands.

A study was made of the role of the adrenergic mechanisms in the activation of endocrine testicular function of CBA/Lac and A/He male mice induced by the presence of a female in estrus without any tactile contact with a male. The alpha 1-adrenoreceptor blocker prazosin inhibited completely an increase in the peripheral blood plasma testosterone level caused by the receptive female challenge. At the same time, optimol blockade of beta 2-adrenoreceptors markedly increased the stimulating effect of the receptive female presence on the blood testosterone level. The expression of optimol action on the blood testosterone level depended on a male genotype. A conclusion was made that during sexual motivation in male mice caused by the presence of a receptive female, the stimulatory effects on testicular endocrine function were produced through the alpha 1-adrenoreceptors and the inhibitory effects were produced through the beta 2-adrenoreceptors.

The levels of serotonin and 5-hydroxyindoleacetic acid contents were estimated in hypothalamus, hyppocampus and midbrain of inbred mice of 12 strains. The levels of serotonin and its metabolite in various parts of brain representing different links of its serotoninergic system were shown to be genetically determined. The correlation analysis revealed that there were two, relatively autonomous genetic systems controlling biosynthesis and catabolism of serotonin in brain.

A study was made of the role of the adrenergic and dopamine mechanisms in the activation of endocrine testicular function of CBA/Lac and A/He male mice induced by the presence of a female in estrus without any tactile contact with a male. The alpha-adrenoreceptor blocker phentolamine inhibited an increase in the peripheral blood plasma testosterone level caused by the receptive female challenge. Propranolol blockade of beta-adrenoreceptors sharply increased the stimulating effect of the receptive female presence on the blood testosterone level. The expression of adrenoblocker action on the blood male sex hormone level depended on a male genotype. The dopamine receptor blocker pimozide produced a moderate effect on the blood testosterone but an attempt to separate its influence into the male sex hormone tonic secretion and the blood testosterone level against a background of sex activation failed. It was concluded that the adrenergic mechanisms were involved in the hypothalamo-hypophyseotesticular complex activation induced by the receptive female presence.

The experiments were performed on rats of three inbred strains (Wistar, August, and Spreg-Dowley). Arterial pressure was measured during acute emotional stress. The reactivity of arteries to vasopressor stimuli, the corticosteroid function, and the humoral pressor activity of plasma were also studied to investigate some physiologic mechanisms of genetically determined differences in the level of arterial pressure during stress. It was established that the rat strains which were examined did not differ in the level of arterial pressure at rest, but showed marked differences in pressure under conditions of stress: the greatest rise in pressure was noted among August rats, the least among Wistar rats, while animals of the Spreg-Dowley strain occupied an intermediate position. It is concluded that inter-strain differences in the pressor reaction reflect genetical peculiarities in the system of nonspecific stress reactivity of animals.