Male Laboratory Mice Research Articles

Pain reduces sexual motivation in female but not male mice.

Chronic pain is often associated with sexual dysfunction, suggesting that pain can reduce libido. We find that inflammatory pain reduces sexual motivation, measured via mounting behavior and/or proximity in a paced mating paradigm, in female but not male laboratory mice. Pain was produced by injection of inflammogens zymosan A (0.5 mg/ml) or λ-carrageenan (2%) into genital or nongenital (hind paw, tail, cheek) regions. Sexual behavior was significantly reduced in female mice experiencing pain (in all combinations); male mice similarly treated displayed unimpeded sexual motivation. Pain-induced reductions in female sexual behavior were observed in the absence of sex differences in pain-related behavior, and could be rescued by the analgesic, pregabalin, and the libido-enhancing drugs, apomorphine and melanotan-II. These findings suggest that the well known context sensitivity of the human female libido can be explained by evolutionary rather than sociocultural factors, as female mice can be similarly affected.

Interrelationship between NO and androgenic activity in mice, Mus musculus, following temporal phase relation of serotonergic and dopaminergic neural oscillations

The present study was designed to monitor the correlation of gonadal steroidogenic activity and nitric oxide (NO) of plasma and testis of male laboratory mouse, Mus musculus, under (1) control/basal and (2) experimental conditions. In the first study, male mice (n = 6) of three age groups (3-week-old sexually immature, 9-week-old sexually mature and 1.5-year-old) were assayed for plasma testosterone and level of NO in the plasma and testis. The immunoreactivity of 3-β-hydroxysteroid dehydrogenase (3-β-HSD) and androgen receptors (ARs) was also detected in testis and epididymis, respectively. In the second study, the reproductive state of mice was altered by injecting precursors of serotonin 5-hydroxytryptophan (5-HTP) and dopamine L-dihydroxyphenylalanine (L-DOPA) daily for 13 days. In one subgroup, mice received their daily injections 8 h apart and in another subgroup 12 h apart. A third subgroup of control mice received two daily injections of normal saline. After the completion of the experiment, the mentioned parameters were measured. The results showed a significant increase in levels of NO and a lowering of the immune reactivity of 3-β-HSD and AR, in both leydig cells and the epididymis in the sexually immature, old-age mice as well as in the mice that received 5-HTP and L-DOPA in the 8-h temporal relation, whereas opposite effects were observed in the sexually mature mice as well as in the mice that received 5-HTP and L-DOPA in the 12-h temporal relation. These findings led us to conclude that an inverse correlation exists between testicular steroidogenic activity and NO activity of laboratory mice under control and experimentally modulated gonadal conditions.

The effect of silver nanoparticles and thioacetamide on blood urea nitrogen and creatinine in male laboratory mice

The effect of silver nanoparticles and thioacetamide on blood urea nitrogen and creatinine in male laboratory mice

The contribution of gut microflora to paracetamol metabolism

During the last decade, the important role of gut microflora as a special organ of the gastrointestinal system in the metabolism of drugs is well known. The aim of this study was to evaluate the role of the gut microecological population with enzymatic systems, especially beta-lyase, in the metabolism of paracetamol in mice. Two groups of 20 white male laboratory mice BALB/c, body weight 32+/-1.5 kg, were treated orally with neomycin sulphate (500 mg/kg in saline solution) and saline solution (10 ml/kg) twice daily for three days. After the treatment, the animals were given paracetamol dissolved in saline solution (200 mg/kg) intraperitoneally. The total amount of excreted paracetamol in 8 hours? collected urine was unchanged. A difference between treated and control mice was observed regarding a highly significant reduction in the excretion of 3-methylthiometabolites. A decrease in the excretion of thiomethyl metabolites was found in the control group compared to the experimental mice. Gut microflora had a great influence on the formation of metabolic precursors, thiomethyl-conjugates, and their oxidabile products. It is obvious that the ecosystem of gut microflora has an important role in the metabolism of paracetamol resulting in a significant reduction in the excretion of 3-methylthioparacetamol by urine, the glucuronide and sulphate.

GENETIC FEATURES of DEVELOPMENTAL PATTERNS OF AGONISTIC BEHAVIOR IN LABORATORY MALE MICE UNDER SOCIAL HIERARCHY CONDITIONS

Background. Agonistic behavior is necessary for formation of dominant-subordinate relationship and for maintenance of social hierarchy in animal communities. However? there are few reports about the genetic features of agonistic behavior development in animals living in stable social groups. The aim of the present study was to investigate the ontogeny of agonistic behavior in male mice of different genotype and social status under stable social hierarchy conditions. Materials and methods. We studied the age dynamics of offensive attacks, the vertical defensive postures and the “runaway” behavior in male mice of inbred strains PT and CBA/Lac housed in genetically heterogeneous pairs during puberty (from 38 to 70 days of life). Results. Dominant-subordinate relationships were stable in 80 % of pairs during the experiment. During the period of stable social hierarchy we observed a transient increase in the number of offensive attacks at the end of puberty in dominants of the strain CBA/Lac but not in PT. Conclusion. In conclusion, the study revealed a significant influence of social rank and genotype on the development of patterns of social behavior in laboratory male mice during puberty.

The change of splenic morphometric parameters in aged laboratory animals exposed to ionizing radiation after undergoing stem cells transplantation

Aim. To study the changes of splenic morphometric parameters in aged laboratory animals exposed to ionizing radiation in the dose of 4Gr after multipotent mesenchymal and hematopoietic stem cells transplantation. Methods. The experiments were conducted on 72 white male laboratory mice at the third year of life with the body weight of 50 g. Multipotent mesenchymal stem cells and hematopoietic stem cells were obtained from 8 laboratory female mice with the body weight of 30 g aged 3-4 months, the gestation term was 14 days. The first group (36 animals exposed to radiation) was subdivided to 2 subgroups of 18 animals each. The suspension of multipotent mesenchymal stem cells (6 000 000 cells/kg) and hematopoietic stem cells (330 000 cells/kg) was introduced as single intravenous injection to the experimental subgroup (18 animals) 1 hour after the animals were exposed to radiation. The animals of control subgroup (18 animals) were injected 0.2 ml of normal saline. The second group included two subgroups 18 mice each that underwent the same procedure without being exposed to radiation. 9 animals from each group were withdrawn from the study at 1st and 7th day each. The lymphoid follicle gross area, area of the T-cell and B-cell zones, general numbers of cells in the red pulp of spleen, including erythrocyte and lymphocyte count, were measured in splenic histologic specimens using the morphometric «BioVision 2008» software. Results. It was shown that on the 7th day after exposure to ionizing radiation followed by stem cells transplantation, the area of thymus-independent zone of lymphoid follicle restored back to normal ranges. The effect of multipotent mesenchymal stem cells and hematopoietic stem cells transplantation also resulted in the increase of the number of cells in the red pulp of spleen. There were no significant changes observed in numbers of erythroid cells and white blood cells in the spleen red pulp compared to control subgroup. At the same time, the leukocyte number in the red pulp of spleen restored to normal values. Conclusion. The restoration of the basic morphometric parameters in spleen of aged laboratory animals exposed to ionizing radiation may be explained be increased homing of splenic colony-forming units with subsequent activation of extramedullary hematopoiesis in spleen, and apoptosis-reducing effect of multipotent mesenchymal stem cells.

The Effect of Etoposide Drug on Chromosomal Changes and Mitotic Index in Mouse Bone Marrow Cells

Etoposide is one of the important chemical drugs commonly used worldwide in the treatment of many cancers and it is classified as an anti metabolic drug as it disrupt the process of multiplication of DNA in cancer cells by inhibiting DNA topoisomerase II causing the death of cancer cells. We select short-term tests in the current study, because it is a quick and accurate indicator to study the effect of chemicals and drugs on biological systems. As there are changes can determined accurately by cytological examination. Laboratory male mice of pure SWR / J were exposed to three types of concentrations (20, 40, 60 mg / kg) of Etoposide at different times to study its effect on the index rate of indirect cell division, and the extent of chromosomal abnormalities that can be caused. Treatment with Etoposide drug led to significant decrease in the index rate of cell division and significant increase of chromosomal abnormalities, and it correlates directly with concentration and inversely with the passage of time after treatment.

DEVELOPMENTAL PATTERNS OF SNIFFING BEHAVIOR IN male laboratory MICE in conditions of SOCIAL COMPETITION

Sniffing behavior plays a significant role for communication and maintenance of the ethological structure of population. We studied the number of nose-nasal and nose-anogenital sniffing in male mice of inbred strains PT and CBA/Lac housed in genetically heterogeneous pairs during puberty and later (from 41 to 70 days of life). Male mice of the CBA/Lac strain show a higher number of nose-anogenital and nose-nasal sniffing in comparison with males of the PT strain. Throughout the period of stable social hierarchy we observed a transient increase in the number of sniffing behaviors in dominants and subordinates of the CBA/Lac strain but not in PT. In conclusion, the study revealed a significant influence of genotype and social rank on developmental patterns of sniffing behaviour in laboratory male mice

Modification of the Testicular Function in Laboratory Male Mice during Social Interactions: Effect of Female Presence

The count of spermatozoa in both caudal epididymides, percentage of abnormal spermatozoon heads and of mobile spermatozoa, body weight, weights of the testes and caudal epididymides were evaluated in adult inbred males (PT and CBA/Lac) kept with females for 5 days. Male mice of the same genotypes and age separated from females served as controls. In males kept with females, the weights of the testes increased in PT male mice, the percentage of rapidly mobile spermatozoa increased in CBA/Lac mice, and body weights decreased in males of both genotypes. The morphometric and spermatogenic parameters in laboratory mice were modulated by the presence of a female, but the effect was determined by the male genotype.

Vitamin C attenuates the physiological and behavioural changes induced by long-term exposure to noise

Persistent, high-intensity noise is an environmental pollutant that plays a destructive role in daily life, especially in industrialized communities. Its effects may be reduced by Vitamin C supplementation. This study examined the possibility that pretreatment with vitamin C (100 mg or 200 mg/kg) could attenuate behavioural and anxiogenic effects of prolonged exposure to noise (100 dB for 2 months, 5 days/week, 4 h daily) on male laboratory mice, by using open-field and plus maze tests of emotionality, and by measuring the neutrophils-to-lymphocytes ratio, a physiological stress measure. The effects seen on behaviour in the open field and plus maze were consistent with the hypothesis that noise could be considered as a stressor as it significantly affected six measures of behaviour in the predicted directions. The neutrophil-to-lymphocyte ratio was also increased as a result of noise exposure. Furthermore, there was good evidence from all three procedures that vitamin C supplementation can attenuate the effects of noise. We conclude that vitamin C supplementation can attenuate or prevent the psychological and physiological damage induced by prolonged noise exposure in mice.

First wild XXY house mice

Laboratory house mice (Mus musculus) with the XXY condition can be generated with ease and have been used as a biomedical model. However, although the XXY constitution has been described in humans and many domestic and wild mammal species, and a very large number of wild house mice have been karyotyped previously, no wild individuals of M. musculus with an XXY karyotype have ever been reported. Therefore, it is rather extraordinary that two wild XXY house mice were caught by us on two different farms in northern Italy in 2008. Except for the extra X chromosome, one male had a standard karyotype (2n = 40) and the other, the karyotype of the Cremona metacentric population (2n = 22). In this paper, the phenotype of these two individuals is described. Observations for both of these wild males agree with those of laboratory XXY mice, i.e., they had a normal body mass and appearance, but significantly smaller testes than normal, and no visible germ cells. The incidence of the XXY chromosome anomaly in wild mice (two among 5,123 wild mice surveyed by us and our colleagues, i.e., approximately 0.08% among wild-caught males) is intermediate between that found in male laboratory mice (approximately 0.04%) and that found in male humans (0.2%).

Metabolic correlates of selection on aerobic capacity in laboratory mice:a test of the model for the evolution of endothermy

According to the aerobic capacity model of the evolution of endothermy, high levels of basal/resting metabolic rate (BMR/RMR) underlying endothermy have evolved as a correlated response to selection for high rates of aerobic metabolism (V(O(2)max)). To test the model we studied metabolic, behavioural and morphological correlates of replicated selection on maximum body mass-corrected metabolism elicited by swimming (V(O(2)swim)) in male laboratory mice. While 10 generations of selection did not change body mass, it resulted in a 12% difference in V(O(2)swim) between mice of selected and control line types and significant, correlated responses in maximum metabolic rates elicited by exposure to cold in a helium-oxygen atmosphere (V(O(2)He)), and during forced running on a motorized treadmill (V(O(2)run)). Selected and control lines also significantly differed with respect to duration of running (a measure of stamina, t(run)), and the distance run to exhaustion (d(e)). However, the selection protocol did not result in elevated BMR and voluntary activity. Higher V(O(2)max) in selected animals was positively correlated with higher masses of gastrocnemius muscles and heart but not of other visceral organs (intestine, stomach, liver and kidneys). These findings provide a mechanistic explanation for the lack of correlation between basal and maximal metabolic rates in selected mice. Overall, our study does not support the assumptions of the aerobic capacity model for the evolution of endothermy.

Effect of 1-(2, 4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (DICA) on the sex organs of the male laboratory mouse.

Oral administration (50 mg/kg body weight/day, for 28 days) of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid (DICA) induced significant reduction in testicular weight with suppression of spermatogenesis. The seminiferous tubules were devoid of spermatozoa and contained only Sertoli cells, spermatogonia, spermatocytes and several multinucleated giant cells. The Leydig cells, however, remained unaffected in treated animals. The drug also induced significant decrease in the levels of testicular RNA and protein; DNA level, however, remained unaltered. Epididymis in DICA-treated mice presented normal histology except that the lumen contained sperm debris; cauda epididymidal spermatozoa were immotile and often fragmented. DICA treatment caused no change in the level of fructose in the seminal vesicle. DICA-induced alterations were reversible and within 56 days of drug withdrawal the reproductive organs returned to their normal state.

Prostaglandin F2 alpha-induced changes in the sex organs of the male laboratory mouse.

Administration (3 mg/kg body weight/day, for 21 days) of prostaglandin F2 alpha (PGF2 alpha) caused marked suppression of spermatogenesis and significant reduction in the weights of the testis, epididymis and accessory sex glands. The seminiferous tubules were devoid of spermatozoa and contained only Sertoli cells, spermatogonia, spermatocytes and occasionally spermatids; several multinucleated giant cells were observed in the lumen of the tubules. The Leydig cells were atrophied. The levels of RNA, DNA and protein in the testis were, however, unaffected by drug therapy. In drug-treated mice the epididymal epithelium presented a degenerate appearance; the lumen was generally devoid of spermatozoa and contained mainly exfoliated immature germ cells and sperm debris; cauda epididymidal spermatozoa, when present, were immotile and fragmented. PGF2 alpha treatment also caused significant decrease in the levels of sialic acid in the caput and cauda epididymides and of fructose in the seminal vesicle. The results suggest that the regressive changes induced by PGF2 alpha in the reproductive organs of the mouse are due to the interference with the secretion of androgen. The alterations induced in the reproductive organs by administration of PGF2 alpha were reversible and 56 days after drug withdrawal the organs returned to their normal state.

Reversible antifertility effect of aqueous rhizome extract of Curcuma longa L. in male laboratory mice

Background The purpose of the present study was to evaluate the antifertility potential of Curcuma longa L . in the male laboratory mouse. Study Design Mice of the Parkes (P) strain were orally administered aqueous rhizome extract of C. longa (600 mg/kg body weight per day for 56 and 84 days), and effect of the treatment on various male reproductive endpoints and fertility was evaluated. Recovery studies were also performed. Results Histologically, testes in mice treated with the plant extract showed nonuniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; the affected tubules showed loosening of germinal epithelium, intraepithelial vacuolation and mixing of spermatids of different stages of spermatogenesis. Marked reductions in diameter of seminiferous tubules, height of germinal epithelium and number of germ cells in Stage VII tubules were also noted in testes of extract-treated mice. Epididymis and seminal vesicle also showed histological alterations. Furthermore, the treatment had adverse effects on motility, viability, morphology and number of spermatozoa in the cauda epididymidis, levels of sialic acid in the epididymis and fructose in the seminal vesicle, serum level of testosterone and on fertility and litter size. By 56 days of treatment withdrawal, however, the above parameters recovered to control levels. Conclusions The results show that in P mice C. longa treatment causes reversible suppression of spermatogenesis and fertility, thereby suggesting the potential of this plant in the regulation of male fertility.

Effects of ELF-EMF on Brain Proteins in Mice

Effect of electromagnetic low frequency fields was studied on mice. We analyzed level of protein in brain of mouse. The levels of c-Jun and c-Fos in brains were measured using Western-blot techniques. Female and male laboratory mice were exposed for 4 days to magnetic field (Bm = 2 mT, f = 50 Hz). The exposure took place in cylindrical coil at laboratory temperature. After the experiment they were sacrificed and the level of protein c-Jun and c-Fos in different parts of brain were estimated. The expression of c-Fos was not affected by magnetic field on the other hand the expression of c-Jun decreased after magnetic field exposure. The results did not depend on sex of mice.

Immunodepression reduces learning performance in male laboratory mice ( Mus musculus)

Several theoretical and empirical studies have suggested that immunocompetence may act as a constraint on learning, due to a trade-off in investment in the two processes. Here we tested whether experimentally depressing immune responsiveness of male BKW mice using antithymocyte serum (ATS) would lead to reduced learning performance in a radial maze task. Correct choices in the maze were indicated by the presence of familiar odours, incorrect choices by unfamiliar odours. We showed that temporarily depressing cellular immunity led to a reduction in performance in terms of a reduced proportion of correct choices. We also found a positive relationship between the proportion of correct entries over the period of testing and haemagglutination titre, indicating that mice showing greater immune responsiveness performed better in the maze. We conclude that depressing the immune system reduces learning performance in a combined odour/spatial learning task, and that some individuals are better able to compensate for the experimental immunodepression. In contrast to previous studies, there was no evidence that the effect of ATS was mediated by associated changes in corticosterone or testosterone secretion. There were no significant effects of the presence of female odour on learning performance, and therefore no evidence that the down regulation of learning in relation to immune depression was influenced by apparent reproductive opportunity.

Evaluation of antifertility potential of Brahmi in male mouse

Background The purpose of the present study was to evaluate the effect of Bacopa monnieri (Brahmi) on fertility of male laboratory mouse. Study Design Mice of the Parkes (P) strain were orally administered Brahmi (250 mg/kg body weight/day, for 28 and 56 days), and effect of the treatment on reproductive organs and fertility was investigated. Recovery and toxicological studies were also carried out. Results The treatment caused reduction in motility, viability, morphology, and number of spermatozoa in cauda epididymidis. Histologically, testes in mice treated with the plant extract showed alterations in the seminiferous tubules, and the alterations included intraepithelial vacuolation, loosening of germinal epithelium, exfoliation of germ cells and occurrence of giant cells. In severe cases, the tubules were lined by only Sertoli cells or Sertoli cells, spermatogonia and spermatocytes. Significant reductions were also noted in height of the germinal epithelium and diameter of the seminiferous tubules in Brahmi-treated mice compared to controls. Epididymis in treated males showed slight alterations in histological appearance. The treatment had no effect on levels of testosterone, alanine aminotransferase, aspartate aminotransferase and creatinine in blood serum, hematological parameters and on liver and kidney histoarchitecture. In Brahmi-treated males, libido remained unaffected, but fertility was notably suppressed. The alterations caused in the above reproductive endpoints by the plant extract were reversible, and by 56 days of treatment withdrawal, the parameters recovered to control levels. Conclusions The results in P mice thus suggest that Brahmi treatment causes reversible suppression of spermatogenesis and fertility, without producing apparent toxic effects.

Tissue-specific characterisation of DNA methylation in the gonad-specific proto-oncogene, c-mos, in the male laboratory mouse.

The proto-oncogene, c-mos, which is expressed only in the germ cells of both testis and ovary, plays an important role in meiotic maturation of these cells. In this research, the methylation status of several CpG sites, present both upstream and within the coding region of the c-mos gene, has been studied. The HpaII and HhaI sites examined in the 5' half of the coding region were unmethylated in both the c-mos expressing and non-expressing tissues. A HhaI site, h3, present 380bp downstream of the transcription start site, was unmethylated in germ cells, but was partially methylated in the somatic tissues, inversely correlating with the expression status of the gene. In contrast to these tissues, in the mouse fibroblast cell line L929, all the analysed sites were completely methylated.

Characterisation of developmentally regulated chromatin structure in the coding region of the proto-oncogene, c-fos, in the male laboratory mouse.

In mouse, tissue-specific developmental de novo methylation of the proto-oncogene c-fos, which is abundantly expressed during embryonic stages, occurs perinatally (between the day of birth to 20 dpp) and is maintained in the adult. In liver, where c-fos is only active up to the day of birth, the gene has more sites methylated than in brain, where it is expressed until about day 5 post-partum. We have studied chromatin organisation of c-fos and compared thisto DNA methylation in the fetal and adult brain and liver. Purified nuclei of these tissues from fetus as well as adult were digested with the restriction enzyme Mspl. DNA was extracted from the Mspl digested chromatin and probed with two DNA segments covering the major part of the body of the gene (from distal part of second exon to major part of fourth exon). Southern hybridisation studies revealed that in the fetus, in both liver and brain, the chromatin in the coding region was sensitive to Mspl digestion and the extent of sensitivity was nearly the same between the two. In the adult tissues, however, chromatin from brain was almost as sensitive as in the fetus, but in the liver it was highly resistant to Mspl. We suggest that a shift from the undermethylated state in the fetus to the heavy methylated state in the adult causes a corresponding change in the organisation of chromatin of c-fos in the coding region. Furthermore, the difference in the tissue-specificity in the methylation induced chromatin compaction could be due to differences in the transcription levels of c-fos and de novo methylation during early neonatal development.