The effect of selected amino acids on gelatin-induced inflammation in adult male mice

Several studies have indicated to us that certain amino acids may exhibit antiinflammatory activity. In the present study we attempted to evaluate the inhibitory effect of various amino acids on gelatin-induced abdominal inflammation in mice using peritoneal fluid cytology as the diagnostic tool. TheL-amino acids tested were tryptophan, phenylalanine, alanine, cystine, hydroxy-proline, tyrosine, citrulline, leucine, and valine. Hydrocortisone was used as an antiphlogistic steroid control. Tryptophan, phenylalanine, alanine, cystine, hydroxyproline, and tyrosine all significantly decreased the inflammation. Citrulline and valine, however, both exhibited strong antiinflammatory responses. Based on these results, three related dipeptides were also screened:L-valyl-L-alanine,L-valyl-L-tryptophan, andL-tyrosl-L-valine. Valyl alanine was found to produce a strong antiinflammatory effect. In a final test, the combination of the steroid, hydrocortisone, and the amino acid, cystine, was screened for a synergistic effect. The combined treatment inhibited the gelatin-induced inflammation more than either the amino acid or the steroid administered alone.     

Reduction in testosterone concentration and its effect on the reproductive output of chronic malaria-infected male mice

An experimental host-parasite association involving BALB/c male mice infected with Plasmodium chabaudi chabaudi was used in order to investigate the influence of the parasite on the sexual physiology and behavior of infected hosts. Infected males displayed complete courtship behavior leading to ejaculation and sired litters on several occasions. A weekly assay of testosterone and corticosterone plasma concentrations revealed a twofold decrease in the testosterone level at 4 and 5 weeks post-injection, during recrudescence. This imbalance was accompanied by a decrease in the overall duration of the social investigation contacts occurring during courtship and by a reduction in the fertilization rate of the infected animals. These physiological perturbations can be regarded as an adaptive response of the host to the recrudescing parasites, which illustrates the rodents capacity for regulating the testosterone profiles needed to balance the competing demands of immunity and reproduction.     

Effects of isomeric fatty acids on reproductive parameters in mice

PROBLEM: The aim of this study was to determine if dietary fatty acids (FA) level or isomeric FA type may affect reproductive parameters in mice. METHOD: of study Mice were fed for 1 month diets differing in cisFA (cFA) content or type of isomeric FA. Resorption, number of fetuses and placental cytokine expression were determined and sperm acrosome reaction was evaluated after induction by calcium ionophore. RESULTS: Mice fed high fat diets showed increased fetal resorptions, a decrease in interleukin (IL)-4 placental expression in the first generation and an increase of tumor necrosis factor-alpha (TNF-alpha) in the second generation. In this generation, conjugated linoleic acid (CLA) returned TNF-alpha to normal levels and diminished IL-4 and transforming growth factor-beta (TGF-beta) expressions; males fed transFA (tFA) and CLA showed a lower rate of induced acrosome reaction. CONCLUSION: The amount and type of dietary FA may affect reproductive performance in mice by affecting sperm membrane functionality and placental cytokine production.     

Adverse effect of tetracycline and doxycycline on testicular tissue and sperm parameters in CD1 outbred mice

Tetracycline and doxycycline are commonly used antibiotics in acne treatment during puberty in humans. The long-term effect of these antibiotics on male reproductive tract development has not been fully elucidated. For this reason we tested the effect of antibiotics on the reproductive parameters of mice males during puberty with the therapeutic dose used in humans, and with lower and higher doses. The outbred mouse strain CD1 with higher heterozygosity was exposed for 14 days at puberty. Adult males at the age of 70 days were used for the measurements. We observed a significant decrease in anogenital distance and thickness of the seminiferous epithelium in the treated animals. Pathological changes in the testes had an impact on sperm quality; a higher number of sperm positively stained with Annexin V and TUNEL and a lower number of acrosome-intact sperm was detected. In conclusion, the treatment of male mice with antibiotics in puberty led to long-lasting effects on reproductive organs and spermatozoa in adult males.     

鼠巨细胞病毒感染对雄性小鼠生殖性激素水平的影响

目的研究鼠巨细胞病毒（MCMV）感染后雄性小鼠生殖性激素水平的变化，探讨MCMV感染影响雄性生殖功能的可能机制。方法选择无McMV活动感染的雄性小鼠，睾丸接种MCMV或不合MCMV的细胞培养液，设立实验组与对照组，采用放射免疫法检测接种后不同时段（小鼠一个生精周期内）的小鼠血清及睾丸组织内性激素含量，并进行比较。结果睾丸匀浆组织T浓度在MCMV感染第4～9d显著降低（P〈0．05），第14～21d有一短暂恢复过程，第38d又较对照组下降（P〈0.05）。血清LH浓度在MCMV感染的第4、9、14d显著升高（P〈0．05），其它时间点比较差异无统计学意义（P〉0．05）。而感染不同时期的血清T和FSH比较差异均无统计学意义（P〉0．05）。结论MCMV急性感染可引起雄鼠生殖内分泌激素水平的改变：通过影响其下丘脑-垂体-性腺轴的调节导致雄鼠生殖功能障碍。     

Toxic effects of citrinin on the male reproductive system in mice

This study investigated the effects of citrinin (CTN) on male mouse reproductive organs. Adult male mice were exposed to intraperitoneal injection of CTN at 0–6.25 mg/kg body weight daily for 7 days, and then mated with sexually mature untreated female mice. Reproductive organ relative weights, semen quality, serum testosterone concentrations and fertility of treated mice were assessed. CTN significantly increased relative weights of the testes, epididymis, seminal vesicle and preputial gland, increased the number of abnormal spermatozoa and decreased the number of live spermatozoa. A significantly lower pregnancy rate was observed when females were mated with CTN-exposed males. The histological results indicated that distance of testicular seminiferus tubule increased. The sperm count and serum testosterone concentrations were significantly reduced in a dose-dependent manner in mice treated with CTN. The results suggest that CTN has adverse effects on the reproductive system of adult male mice.     

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits

This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits.     

Evaluation of in vivo reproductive toxicity of potassium chromate in male mice

To evaluate the effects of potassium chromate on mice sperm cells after a short-term exposure, male ICR-CD1 mice were administered with 5 or 10 mg K₂CrO₄/bw for 4 consecutive days. One group of mice was sacrificed at day 5, starting from the beginning of the experiment and another group was sacrificed at day 35. Testis and epididymis histology was evaluated by light microscopy and testicular cells populations were evaluated by flow cytometry (FCM). Spermatozoa were collected from the epididymis and their morphology and several functional parameters (density, motility, viability, mitochondrial function, acrosome integrity) were evaluated. Furthermore, DNA fragmentation and chromatin status of sperm cells were assessed at both experimental periods.Besides a reduction in seminiferous tubules diameter, exposure to potassium chromate did not induce further histopathological changes in mice testis or epididymis. These results were supported by the analysis of testicular cellular subpopulations by FCM. Concerning spermatozoa morphology, an increase in the percentage of multiple abnormalities and a decrease in the percentage of normal spermatozoa were found at days 5 and 35, respectively. Although spermatozoa mitochondrial function or viability was not affected, its motility was significantly reduced by potassium chromate exposure at both experimental periods. A decrease in acrosome integrity was found in mice injected with 10 mg K₂CrO₄/bw after 35 days. Exposure to potassium chromate did not affect either DNA fragmentation or chromatin susceptibility to acid denaturation of sperm cells. In this work, we were able to show the effects of potassium chromate on spermatozoa physiological parameters such as motility, morphology and acrosome status and also demonstrate that the doses tested did not induce DNA damage to sperm cells after one spermatogenic cycle.     

Diabetes mellitus- induction: Effect of different streptozotocin doses on male reproductive parameters

Diabetes mellitus (DM) is reported to be involved in male reproductive impairment, and its impact is evident in the increased prevalence of infertility. Various studies have reported that a single parenteral injection of <40?mg/kg Streptozotocin (STZ) is ineffective in ablating pancreatic β-cells and creating a rat model to investigate the effect of DM on the male reproductive system. This study therefore aims to validate these claims.Adult male Wistar rats received either a single intraperitoneal injection of STZ (30?mg/kg or 60?mg/kg) or saline (0.9%, Control). Diabetes was confirmed after 72?h if plasma glucose levels were ≥14?mmol/L. Body weight, glucose level, fluid and food intake were measured weekly. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160?mg/kg body weight). The testis and epididymis were harvested and weighed prior to preparation for histological evaluation. Epididymal sperm morphology was analysed using computer aided sperm analysis (CASA). STZ60 animals presented with significantly lower body weights compared to both control and STZ30 groups. Animals in both STZ30 and STZ60 groups showed decreased normal sperm morphology compared to control. Histological evaluation of the testes showed a decrease in the number of spermatozoa in the seminiferous tubules of animals in the STZ30 and STZ60 groups compared to control. A complete absence of spermiogenesis was observed in the seminiferous tubules of STZ60 animals. These findings prove that an STZ concentration of 30?mg/kg, which is much lower than the reported 40?mg/kg, has adverse effects on the male reproductive system via its diabetogenic effect and can therefore be used to study the impact of DM on male fertility.     

Behavioral effect of terahertz waves in male mice

We studied the effect of terahertz waves (3.6 THz, 81.5 μ, 15 mW) on the behavior of mice. The mice perceived terahertz waves even after short-term exposure (15 min). The effect of terahertz waves was maximum in direct contact of the mice with the laser. Increased anxiety of experimental animals was observed on the next day after 30-min irradiation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 378–382, April, 2008     

Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats

Introduction

Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity.

Material and methods

Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed.

Results

The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.

Conclusions

The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.     

Patterns of violent aggression-induced brain c-fos expression in male mice selected for aggressiveness

Mice selected for aggressiveness (long and short attack latency mice; LALs and SALs, respectively) constitute a useful tool in studying the neural background of aggressive behavior, especially so as the SAL strain shows violent forms of aggressiveness that appear abnormal in many respects. By using c-Fos staining as a marker of neuronal activation, we show here that agonistic encounters result in different activation patterns in LAL and SAL mice. In LALs, agonistic encounters activated the lateral septum, bed nucleus of stria terminalis, medial amygdala, paraventricular nucleus of the hypothalamus, anterior hypothalamic nucleus and tuber cinereum area (both being analogous with the rat hypothalamic attack area), dorsolateral periaqueductal gray, and locus coeruleus. This pattern is similar with that seen in the territorial aggression of male mice, rats and hamsters, and non-lactating female mice. SALs showed strong fight-induced activations in the central amygdala and lateral/ventrolateral periaqueductal gray. In this strain, no activation was seen in the lateral septum and the dorsolateral periaqueductal gray. This pattern is similar with that seen in other models of violent aggression, e.g., in attacks induced by hypothalamic stimulation in rats, quiet biting in cats, lactating female mice, and hypoarousal-driven abnormal aggression in rats. We suggest here that the excessive activation of the central amygdala and lateral/ventrolateral periaqueductal gray--accompanied by a smaller activation of the septum and dorsolateral periaqueductal gray--underlay the expression of violent attacks under various circumstances.     

卵泡刺激素受体(FSHR32-44)肽疫苗对雄性小鼠生殖器官影响

目的探讨FSHR32-44肽疫苗对雄性小鼠的生殖器官及机能影响。方法 Balb/c雄性小鼠随机分FSHR32-44(20μg)组、FSHR32-44(80μg)组、FSHR140蛋白组及PBS组(对照组),用竞争性RIA法检测血睾酮水平、HE染色观察睾丸及附睾组织病理改变、硝酸镧示踪法观察血睾屏障的超微结构变化。结果 FSHR32-44(20μg)组、FSHR32-44(80μg)组、FSHR140蛋白组及PBS组(对照组)的血睾酮水平分别为(2.65±0.34)%、(2.63±0.25)%、(2.4±0.56)%及(2.7±0.28)%,肽组与对照组比较,睾酮水平变化无统计学差异(P>0.05);蛋白组与对照组比较,睾酮水平下降(P<0.05)。光镜下肽组及蛋白组中的睾丸及附睾精子数减少,但蛋白组中睾丸的精原细胞出现水肿及点状坏死;电镜下肽组的血睾屏障无损伤。结论 FSHR32-44肽疫苗免疫小鼠后,无论低剂量还是高剂量对生殖器官及性激素不产生任何影响。     

Effects of dietary isoflavone aglycones on the reproductive tract of male and female mice

We assessed the effects of dietary consumption of soy isoflavone aglycones on the reproductive tract of sexually mature male and female mice. Isoflavone concentrates with a ratio of 10:1, 2:1 or 1:10 genistein:daidzein (G:D) were added to provide 120 mg total isoflavones/1800 Calories (approximately 40 mg/kg body weight) to diets having either casein/lactalbumin or soy protein isolate as the source of protein. After 16 weeks, mice were necropsied and gross and histopathologic assessments of uterus, vagina, testes and accessory sex glands were completed. Effects of the 10G:1D isoflavone concentrates were absent or minimal in females but in males included atrophy of accessory sex glands. In contrast, the 2G:1D and 1G:10D concentrates caused dramatic estrogenic effects in both male and female mice. Effects in females included endometritis and effects typical of estrogenic stimulation (i.e., uterine enlargement, keratinization of vaginal epithelium, increased height of endometrial surface epithelial cells, and uterine squamous metaplasia). Effects in males included reduced plasma testosterone concentrations, atrophy of seminiferous epithelium, atrophy of accessory sex glands, and squamous metaplasia of seminal vesicles. Some effects varied with protein source. We conclude that a diet containing approximately 40 mg/kg soy isoflavone aglycones with a genistein:daidzein ratio of 2:1 or less has marked estrogenic effects on the reproductive system of male and female mice.     

Female genotype influences the behavioral performance of mice selected for reproductive traits.

The behavioral performance of mice that differ in regularity of the estrous cycle and litter size was studied after female exposure to a male of the same or a different strain. Emotional reactivity was measured using the pole, straightaway and open field tests. Factor interpretations of emotionality included motor discharge, autonomic imbalance and acrophobia. Mice characterized by regular estrous cycles and large litters (line E) were more explorative and emotionally reactive with respect to motor discharge and autonomic imbalance. In contrast, mice with less regular estrous cycles and small litter size (line CN-) were more acrophobic. These strain differences in behavioral performance were influenced by the genotype of the female rather than the cohabitating male.     

Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats

Using immunohistochemical methods, we studied the cell-type- and species-specific expressions of estrogen receptor (ER) isoforms (ER alpha and ER beta) and androgen receptors (ARs) in the male reproductive tract and accessory sex glands of mature mice and rats. ER alpha and ER beta showed cell-type- and species-specific distributions, respectively. In contrast, AR was localized in the epithelial and stroma cells of all tissues examined in this study, in both species. In mice, the epithelial cells of the ductuli efferentes showed a strong ER alpha-immunoreaction, and those of the caput epididymis, coagulating glands, and prostate also exhibited a positive reaction. Stroma cells, except in the ductuli efferentes, showed a positive ER alpha-immunostaining. In rats, ER alpha was detected in very few cell types: the epithelial cells of the ductuli efferentes showed a strong reaction, and the stroma cells of the ampullary and urethral glands exhibited a weak reaction. ER beta was localized in the epithelial cells of the prostate in mice, while the reaction was faint or negative in both the epithelial and stroma cells of other tissues. In rats, the ER beta-immunoreaction was strongest in the epithelial cells of the ventral prostate. The epithelial cells of the corpus and cauda epididymis, ductus deferens, and urethral glands, and the stroma cells of the urethral glands were also positively ER beta-immunostained. Almost the same AR distribution pattern was observed in both species. In particular, strong AR-immunostaining was present in the epithelial cells of the caput and corpus epididymis, seminal vesicle, and ventral prostate. These results indicate that species and tissues differences should be taken into careful consideration in assessing the physiological and pharmacological effects of sex steroids (particularly estrogens) on the reproductive tissues of male rodents.     

Perinatal exposure to genistein alters reproductive development and aggressive behavior in male mice

Exposure to endocrine disrupting chemicals adversely affects reproductive development and behavior in males. The goal of this study was to determine if exposure to genistein, an isoflavone found in soy, during early periods of sex differentiation alters reproductive development and behavior in male mice. Female C57BL/6 mice were fed a phytoestrogen-free diet supplemented with 0, 5 or 300 mg/kg of genistein throughout gestation and lactation. Anogenital distance (AGD) and body mass of male offspring was measured weekly from postnatal days 2-21, timing of preputial separation was assessed at puberty, and in adulthood, reproductive organ masses, sperm and testosterone production, and reproductive and aggressive behaviors were assessed. Exposure to genistein resulted in smaller AGD are reduced body mass, with the low-dose diet exerting a greater effect. Timing of preputial separation, adult reproductive behavior, sperm concentrations and testosterone production were not influenced by genistein treatment at either dose. Aggressive behaviors were decreased, whereas defensive behaviors were increased, in males that received the low-dose genistein diet. Exposure to genistein during critical periods of sex differentiation results in concurrent and persistent demasculinization in male mice. Phenotypic and behavioral abnormalities induced by genistein showed a non-monotonic response, where treatment with a low dose exerted a greater effect than treatment with a high dose of genistein. Given the popularity of soy infant formulas, the influence isoflavone exposure on reproductive and behavioral health in boys and men should be considered.