Decreased Testosterone Levels Research Articles

Depression-related Testosterone Deficiency is Linked to Reduced Cholesterol Levels in Leydig Cells of CUMS Mice.

Testosterone deficiency in humans can be caused by depressive symptoms; however, the causes of this deficiency are incompletely understood. This study demonstrates that male mice with depression-like symptoms due to chronic unpredictable mild stress (CUMS) show reduced serum testosterone levels and disrupted sexual behaviors. However, the observed testosterone reductions were not caused by apoptosis of Leydig cells. Oil red O staining revealed that lipid droplets were dramatically decreased in Leydig cells, suggesting that defects in cholesterol uptake might be related to testosterone-deficiency in depression-like mice. To investigate the potential mechanism, lipid homeostasis was examined by liquid chromatography tandem mass spectrometry. The results revealed that higher levels of sphingomyelins (SM 8:0;2O/28:1, 18:0;2O/22:2, 33:0;3O, 33:1;2O) were linked to decreased cholesterol levels. Further investigation indicated that testosterone biosynthesis from cholesterol in Leydig cells was impaired by downregulation of Ldlr, SR-BI, LHR, and P450scc. Elevated levels of interferon signaling associated pathways in depression-like mice testes may also contribute to decreased testosterone level. Taken together, these findings provide a novel understanding of male reproductive problems under psychological stress and suggest that cholesterol uptake might be a causal factor in reduced testosterone production in depression-like mice.

A comprehensive investigation on female Wistar rats examining the therapeutic potential of Pueraria tuberosa on letrozole-induced Polycystic ovarian syndrome

Background Polycystic ovarian syndrome (PCOS) stands out as the most prevalent endocrine disorder affecting women of reproductive age with 5–10% of women experiencing its effects. Historically known as Stein-Leventhal syndrome, its pathology involves various irregularities including heightened androgen levels, insulin resistance, diminished estrogen and progesterone levels, and irregular gonadotropin levels. However, the drugs commonly used to treat PCOS come with multiple side effects and limited efficacy in targeting the disorder’s underlying pathology. Indian kudzu tubers, specifically Pueraria tuberosa (Willd.) DC. tubers are a valuable source of phytoestrogens such as puerarin, daidzein, biochanin-A, and formononetin. Phytoestrogens are natural compounds derived from plants that stimulate estrogenic activity through estrogen receptors (ERα and ERβ), thereby increasing estrogen levels. Hence, the objective of this research was to assess the impact of the ethanolic extract obtained from Pueraria tuberosa (Willd.) DC. on the ovarian steroidogenesis pathway in a rat model with induced PCOS using letrozole. Objective To determine the hormonal parameters i.e. estrogen, testosterone, progesterone, follicle-stimulating hormone and luteinizing hormone level, as well as to evaluate body weight, ovarian weight, and histopathology of the ovary in female rats, we investigated a comprehensive investigation on female Wistar rats examining the therapeutic potential of Pueraria tuberosa on letrozole-induced PCOS. Materials and methods For this aim, animals were divided into six groups (n=6). Control group, untreated letrozole-induced PCOS group (1 mg/kg bwt) for 21 days, PCOS group treated with tuber extract of Pueraria tuberosa (Willd.) DC (100 200 and 400 mg/kg bwt) for 14 days, and PCOS group treated with clomiphene citrate (1 mg/kg bwt) for 14 days. Finally, body and ovarian weight, and hormonal assays (estrogen, testosterone, progesterone, follicle-stimulating hormone, and luteinizing hormone levels) were conducted. Histomorphometric ovarian evaluation of cystic follicles was determined. Results and conclusion The ethanolic extract of Pueraria tuberosa (Willd.) DC. tuber exhibited a significant enhancement in both body weight and ovarian weight when compared with the PCOS-induced group. It positively influenced hormonal levels by increasing estrogen and progesterone while decreasing testosterone levels. In addition, the extract normalized the ratio of follicle-stimulating hormone and luteinizing hormone levels and assessed histomorphometric changes, leading to a reduction in cystic follicles. In summary, the ethanolic extract derived from the tuber of Pueraria tuberosa (Willd.) DC. demonstrates the potential to alleviate certain symptoms associated with polycystic ovary syndrome. This positive impact is attributed to its components, including puerarin, daidzein, biochanin-A, and formononetin, which exhibit estrogenic and antiandrogenic effects. Notably, in this study, doses of 200–400 mg/kg of the extract were identified as the most effective, suggesting their promise as a potential therapeutic intervention for PCOS.

Assessment of Dichlorvos, Cypermethrin, Synthetic Camphor, Pinenes, and Kerosene: Impact on Testosterone Levels, Glutathione Concentration, and Testicular Histology in Male Wistar Rats

Pesticides are integral to modern agriculture and public health but pose significant risks to human and environmental health. This study investigates the impact of selected pesticides on male reproductive health via inhalation in an improvised chamber. Male Wistar rats were assigned to groups and exposed to individual pesticides and a combined mixture to determine lethal doses. Tissue samples from 54 rats were analyzed histologically and biochemically for effects on testes and epididymides, with measured serum testosterone and GSH levels. Sniper consistently showed the highest significant decrease in GSH levels across all exposure levels (p < 0.05). A significant dose-dependent relationship was observed in the recovery groups from 25% to 75% exposure (p < 0.05). Pesticide exposure led to a substantial decrease in serum testosterone levels in male Wistar rats at 25% (all pesticides, p < 0.05), 50% (DD Force, Sniper, Kerosene, Combined, p < 0.05), and 75% (DD Force, Industrial Camphor, Edible Camphor, Kerosene, p < 0.01) concentrations. Escalating damage in testicular and epididymal structures, with a more pronounced severity at higher exposure levels, including epithelial degeneration, Sertoli cell vacuolation, seminiferous tubule derangement, and ductal atrophy. Increased exposure to high doses of pesticides induces oxidative stress in male Wistar rats which could potentiate decreased testosterone levels and adversely impact the histological architecture of the testes and epididymides. Pesticide detoxifications are somewhat evident following withdrawal from the environmental insults. Significant and persistent damage occurred at higher levels, suggestive of substantial reproductive toxicity following exposure.

Chronic exposure to polystyrene microplastics induced LHR reduction and decreased testosterone levels through NF-κB pathway

The extensive utilization of plastic products in recent years has resulted in a significant contamination of microplastics (MPs). The ingestion of MPs by aquatic and terrestrial organisms facilitates their transmission to mammals through the food chain. Therefore, the toxicity of MPs has attracted widespread attention from researchers. Previous studies have shown a connection between being exposed to polystyrene MPs (PS-MPs) and issues with male reproductive function. Testosterone, a hormone essential for male reproductive function, is produced and secreted by specialized cells known as Leydig cells, which found in the testicular interstitium. In our prior research, we confirmed that exposure to PS-MPs caused a reduction in testosterone levels by interfering with the LH-mediated LHR/cAMP/PKA/StAR pathway, with LHR being pivotal in this mechanism. However, the molecular mechanism underlying PS-MPs-induced reduction of LHR remains unclear. In this study, mice were respectively given drinking water containing 1000 μg/L PS-MPs characterized by diameters of 0.5 μm, 4 μm, and 10 μm for a period of 180 days. Our findings indicated that exposure to PS-MPs resulted in the proliferation of macrophages as well as their polarization towards the M1 phenotype. Additionally, the presence of PS-MPs triggered the release of tumor necrosis factor alpha (TNF-α) from macrophages, thereby activating nuclear factor-κB (NF-κB) signaling pathway within Leydig cells. The translocation of NF-κB into nucleus facilitated its binding to the promoter region of LHR, which consequently led to the repression of LHR transcription. This transcriptional inhibition resulted in a subsequent suppression of testosterone synthesis and secretion. Overall, this study elucidates a theoretical basis for explaining the interference of PS-MPs on the testosterone synthesis and secretion in Leydig cells from the perspective of the interaction between cells in the testicular interstitium.

The level of sex and fertility hormones in the serum of male patients recovered from COVID-19

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that generated the COVID­-19 pandemic is a broad-spectrum infection that besides the respiratory tract, can attack multiple organs, including­ the digestive, circulatory, and urinary systems. However, the negative consequences of SARS-CoV-2 on the male reproductive system have been largely ignored. The aim of this research was to see how SARS-CoV-2 affects the production of hormones, which are the markers of male reproductive function and fertility. The 350 Iraqi male participants were classified into two groups consisting of 150 COVID-19 recovered patients with a mean age of (32 ± 7.9) years and COVID-19 diagnosis confirmed by RT-PCR, and 200 apparently healthy male volunteers of similar age. The patients’ group was further divided into three groups depending on the recovery period of 3, 5 and 7 months. Serum levels of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin were measured using the Mindray CL-1000i automated chemiluminescence analyzer provided with matching kits. When comparing the indices of COVID-19 recovered participants to the control group, the results revealed a decrease in testosterone level that was positively associated with the recovery period and an increase in the LH, FSH and prolactin levels that were negatively associated with the recovery period. It is supposed that infection with SARS-CoV-2 may be followed by a temporary condition of testicular failure. Keywords: male fertility, SARS-COV-2, sex hormones

Effects of Aerobic Training on Sex Hormones in A Cuprizone Rat Model of Multiple Sclerosis.

Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS.

The protective role of phlorizin against lipopolysaccharide-induced acute orchitis in mice associated with changes in gut microbiota composition

ObjectiveOrchitis is a common reproductive disease of male animals, which has serious implications to human and animal reproduction. Additionally, phlorizin (PHN), a common polyphenol in apples and strawberries, has a variety of biological activities, including antioxidant, anti-inflammatory, anti-diabetic, and anti-aging activities. We aimed to determine the protective effects and potential mechanisms of PHN in lipopolysaccharide (LPS)-induced acute orchitis in mice.MethodAfter 21 days of PHN pretreatment, mice were injected with LPS to induce testicular inflammation, and then the changes of testicular tissue structure, expression of inflammatory factors, testosterone level, expression of testosterone-related genes, adhesion gene and protein expression were detected, and the structural changes in the intestinal flora after PHN treatment were further detected by 16SRNA.ResultOur results demonstrated that PHN treatment reduced LPS-induced testicular injury and body and testicular weight losses. The mRNA expression levels of pro-inflammatory cytokines-related genes and antioxidant enzyme activity were also decreased and elevated, respectively, by PHN administration; however, PHN treatment also reduced the LPS-induced decrease in testosterone levels in the testes. Additionally, further studies found that PHN increased the expression of marker proteins zonula occludens-1 (ZO-1) and occludin associated with the blood testosterone barrier compared with that in LPS treatment groups. To further examine the potential mechanisms of the protective effect of PHN on LPS-induced testicular injury, we compared the differences of gut microbiota compositions between the 100 mg/kg PHN treatment group and the control group using 16SRNA. Metagenomic analyses indicated that the abundances of Bacteroidetes, Muribaculaceae, Lactobacillaceae, uncultured bacterium f Muribaculaceae, and Lactobacillus in the PHN treatment group improved, while potential microbes that can induce intestinal diseases, including Verrucomicrobia, Epsilonbacteraeota, Akkermansiaceae, and Akkermansia decreased in the PHN treatment group.ConclusionOur results indicate that PHN pretreatment might alleviate orchitis by altering the composition of gut microflora, which may provide a reference for reducing the occurrence of acute orchitis in male animals.

Loss of PBX1 function in Leydig cells causes testicular dysgenesis and male sterility

Leydig cells are essential components of testicular interstitial tissue and serve as a primary source of androgen in males. A functional deficiency in Leydig cells often causes severe reproductive disorders; however, the transcriptional programs underlying the fate decisions and steroidogenesis of these cells have not been fully defined. In this study, we report that the homeodomain transcription factor PBX1 is a master regulator of Leydig cell differentiation and testosterone production in mice. PBX1 was highly expressed in Leydig cells and peritubular myoid cells in the adult testis. Conditional deletion of Pbx1 in Leydig cells caused spermatogenic defects and complete sterility. Histological examinations revealed that Pbx1 deletion impaired testicular structure and led to disorganization of the seminiferous tubules. Single-cell RNA-seq analysis revealed that loss of Pbx1 function affected the fate decisions of progenitor Leydig cells and altered the transcription of genes associated with testosterone synthesis in the adult testis. Pbx1 directly regulates the transcription of genes that play important roles in steroidogenesis (Prlr, Nr2f2 and Nedd4). Further analysis demonstrated that deletion of Pbx1 leads to a significant decrease in testosterone levels, accompanied by increases in pregnenolone, androstenedione and luteinizing hormone. Collectively, our data revealed that PBX1 is indispensable for maintaining Leydig cell function. These findings provide insights into testicular dysgenesis and the regulation of hormone secretion in Leydig cells.Graphical abstract

Gonadal efficacy of Thymus quinquecostatus Celakovski: Regulation of testosterone levels in aging mouse models

Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

Benefits of yoga on women with Polycystic Ovarian Syndrome (PCOS)

Polycystic ovary syndrome (PCOS) is a hormonal imbalance that occurs when the ovaries produce and release eggs creating excess hormones. Affected women range in age from 6% to 20%, depending on the diagnostic criteria. Hyperandrogenism and persistent anovulation are two characteristics of the complex condition known as polycystic ovarian syndrome (PCOS). Treatment for PCOS involves lifestyle modifications, education, and symptom-specific therapies for both individuals at risk and those with a confirmed diagnosis. Exercise and dietary changes have long been seen as the cornerstones of managing lifestyle diseases. Yoga is an age-old discipline that aims to balance a person's mental, emotional, physical, and spiritual aspects. Yoga can improve one's physical and mental well-being, making them feel better overall. Several research studies have demonstrated the beneficial effects of yoga in PCOS control. Regular yoga practice has been demonstrated to ease the symptoms of PCOS and decrease testosterone levels, also promoting relaxation. The present paper is intended to bring a thematic insight into the problem related to PCOD and the impact of yoga among the patients of PCOD.

Integrated untargeted and targeted testicular metabolomics to reveal the regulated mechanism of Gushudan on the hypothalamic-pituitary-gonadal axis of kidney-yang-deficiency-syndrome rats.

Modern studies have shown that neuroendocrine disorders caused by the dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis are one of the important pathogenetic mechanisms of kidney-yang-deficiency-syndrome (KYDS). The preventive effect of Gushudan on KYDS has been reported, but its regulatory mechanisms on the HPG axis have not been elucidated. In this study, we developed an integrated untargeted and targeted metabolomics analysis strategy to investigate the regulatory mechanism of Gushudan on the HPG axis in rats with KYDS. In untargeted metabolomics, we screened 14 potential biomarkers such as glycine, lysine, and glycerol that were significantly associated with the HPG axis. To explore the effect of changes in the levels of potential biomarkers on KYDS, all of them were quantified in targeted metabolomics. With the quantitative results, correlations between potential biomarkers and testosterone, a functional indicator of the HPG axis, were explored. The results showed that oxidative stress, inflammatory response, and energy depletion, induced by metabolic disorders in rats, were responsible for the decrease in testosterone levels. Gushudan improves metabolic disorders and restores testosterone levels, thus restoring HPG axis dysfunction. This finding elucidates the special metabolic characteristics of KYDS and the therapeutic mechanism of Gushudan from a new perspective.

Protective effect of Petroselinum crispum methanolic extract against acrylamide-induced reproductive toxicity in male rats through NF-ĸB, kinesin, steroidogenesis pathways

This study examined the protective effects of a Petroselinum crispum (P. crispum) methanolic extract on reproductive dysfunction induced by acrylamide in male rats. A total of 40 rats were divided into four groups (n=10). The control group received distilled water, the acrylamide group received 10 mg/kg of acrylamide, the P. crispum group received 100 mg/kg of P. crispum extract, and the combined group was pretreated with P. crispum for two weeks before co-administration of P. crispum and acrylamide. All administrations were administered orally using a gastric tube for eight weeks. Acrylamide decreased testosterone levels but did not affect levels of FSH or LH. It also increased testicular levels of (MDA) malondialdehyde and reduced activity of (SOD) superoxide dismutase and impairment of sperm parameters. Furthermore, the administration of acrylamide resulted in an elevation of tumor necrosis factor-alpha (TNF-α) levels and a reduction in the levels of steroidogenic acute regulatory protein (STAR) and cytochrome P450scc (P450scc). Acrylamide negatively affected the histopathological outcomes, Johnsen's score, the diameter of seminiferous tubules, and the thickness of the germinal epithelium. It also upregulated the expression of NF-ĸB P65 and downregulated the expression of kinesin motor protein. In contrast, treatment with P. crispum extract restored the levels of antioxidant enzymes, improved sperm parameters, and normalized the gene expression of TNF-α, IL-10, IL-6, iNOS, NF-ĸB, STAR, CYP17A1, 17β-HSD and P450scc. It also recovered testicular histological parameters and immunoexpression of NF-ĸB P65 and kinesin altered by acrylamide. P. crispum showed protective effects against acrylamide-induced reproductive toxicity by suppressing oxidative damage and inflammatory pathways.

Comparative expression and localization of visfatin, chemerin, and chemerin receptor proteins in a heat-stressed mouse testis

The adipokines, visfatin, chemerin, and its receptor are expressed in the testis. It has also been shown that heat-stress alters the secretion and expression of other adipokines. Testicular heat-stress is now well known to cause the impairment in the testis. It has also been documented that heat-stress changes the expression of genes and proteins in the testis. To the best of our knowledge, the expression and localization of visfatin chemerin and its receptor have not been investigated in the heat-stressed testis. Therefore, the present study has investigated the expression and localization of these proteins in the heat-stressed testis. The expression of visfatin and chemerin and receptor exhibits a differential repossess against the heat stress. Visfatin expression was up-regulated while chemerin and chemerin receptor was down-regulated in the heat-stressed testis as shown by western blot analysis. The immunolocalization of visfatin and chemerin showed increased abundance in the seminiferous tubules of heat-stressed mice testis. Furthermore, abundance of visfatin, chemerin, and its receptor showed a decrease in abundance in the Leydig cells of heat-stressed testis. The decreased abundance of these proteins in the Leydig cells coincides with decreased 3β-HSD immunostaining along with decreased testosterone levels. These results suggest that heat-stress might decrease testosterone secretion by modulating visfatin and chemerin in the Leydig cells. The increased abundance of visfatin and chemerin in the primary spermatocytes, round spermatid, and multinucleated germ cells also coincides with increased immunostaining of active caspase-3. Moreover, expression of Bcl-2 was down-regulated, and expression of active caspase-3 and HSP70 were up-regulated along with increased oxidative stress in the heat-stressed testis, suggesting stimulated apoptosis. In conclusion, our results showed that visfatin, chemerin, and its receptor are differentially expressed in the testis under heat-stress and within the testis also it might differentially regulate testosterone biosynthesis in the Leydig cells and apoptosis in the seminiferous tubules.

Evaluation of histopathological patterns and testicular biopsies in infertile male and its relationship with some hormones in Kirkuk/Iraq

Infertility affects between 15% to 20% of couples worldwide, making it a major concern. Testing abnormalities may result in non-obstructive, permanent azoospermia. Infertility affects between 15% to 20% of couples worldwide, making it a common cause for worry. Testing abnormalities may result in non-obstructive, permanent azoospermia. Testicular biopsy is the only procedure available for diagnosing azoospermia. The current study included a cohort of 30 people who had been clinically diagnosed with azoospermia. Additionally, a cohort of 20 healthy male volunteers was enlisted from Kirkuk, Iraq's private laboratories and recruited from Azadi Teaching Hospital. The findings of this study indicate that Sertoli-cell-only-syndrome (39.996%) displayed the highest prevalence in testicular biopsies and it categorized Johnson score2, Testicular atrophy emerged as the second most frequently encountered condition (23.331%) it categorized as the Johnson scoring 1. Followed by germ cell maturation arrest (16.665%) as Johnson score8-3, followed by hypospermatogenesis (9.999%) as Johnson scoring 7, followed by Seminiferous tubule hyalinization (6.666%) as Johnson scoring 1, Subsequently, there was an observed occurrence of normal spermatogenesis, amounting to 3.333%. The study's results indicated that within our particular geographic region, the Sertoli-cell-only syndrome (SCOS) exhibited the highest prevalence among the 30 specimens examined, which were testicular biopsies obtained from infertile males. Furthermore, it was observed that individuals diagnosed with azoospermia showed a statistically significant increase in serum luteinizing hormone levels, while experiencing a statistically significant decrease in testosterone levels.

Androgen State and Erectile Function in Men with Chronic Distress

The objective: to study the state of androgen supply and erectile function in men with chronic distress. Materials and methods. We examined 30 internally replaced males (Average age, M±σ=50.50±3.83) with manifestations of chronic distress (Group I) and 20 practically healthy males (Group II), (Average age, M±σ=51.95±4.60). All men underwent general clinical examination, body mass index evaluation, assessment of depression according to Hospital Anxiety and Depression Scale (HADS), assessment of symptoms of androgen deficiency according to the Aging Males’ Symptoms (AMS). Severity of erectile dysfunction was evaluated according to the International Index of Erectile Function scale (IIEF). The following parameters were determined in blood serum: luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), free testosterone (TF), estradiol (E), cortisol (K). Results. According to the HADS scores in group I men, the average anxiety domain score was 12.03±1.50 points, the average depression domain score was 13.93±1.49, and the total score was 26.0±2.64 points. In patients of group II, the average anxiety domain score was 2.20±0.88 points, the average depression domain score was 2.60±1.00, and the overall score was 4.80±1.40 points. The comparison of the total score of group I and the total score of group II is statistically significant (p&lt;0.05). According to the AMS, in men of group I, androgen deficiency was more expressed comparing to the control group (45.93±3.30 and 13.30±2.04 points, respectively, p&lt;0.001). Analysis of the IIEF-15 questionnaire revealed a decrease in all indicators of erectile function in men of group I comparing to group II. A study of the hormonal state showed a decrease in the level of TT in men of group I compared to the indicators of group II: 9.30±2.84 and 15.27±0.96 ng/ml, respectively (p&lt;0.001). The average TF levels in group I were reduced comparing to group II and reached 10.23±1.38 and 17.39±1.03 pg/ml, respectively (p&lt;0.001). The levels of LH and FSH in men of group I were within normal age-related fluctuations and did not differ statistically significantly from similar levels of group II. The average E level in men with chronic distress was significantly increased comparing to the control group and reached up to 0.25±0.05 versus 0.11±0.03 nmol/l, respectively (p&lt;0.001). The average C level in men with chronic distress was significantly increased comparing the control group and reached up to 13.33±2.19 versus 6.72±1.33 μg/dL, respectively (p&lt;0.001). Conclusions. 1. The survey results indicate that chronic distress is a factor that worsens sexual function in men. In addition to erectile dysfunction, as evidenced by a decrease in the corresponding IIEF integrative indicator 15 «erectile function», the survey found a decrease in both the frequency of occurrence and the degree of sexual desire, a deterioration in orgasmic sensations in the form of a decrease in the frequency of ejaculation and orgasms. 2. Cortisol is an important hormone that forms protective reaction in stressful situations, but loses its positive properties during chronic distress. A prolonged increase in cortisol levels can lead to a pathological condition accompanied by an increase in BMI, depression, anxiety, decreased testosterone levels and ED. 3. A decrease in testosterone levels in chronic distress and visceral obesity in men is not accompanied by a compensatory increase in LH and FSH levels. This can be explained by increased aromatization of testosterone in visceral adipose tissue and a decrease in the pituitary gland’s response to the development of androgen deficiency as a result of combined damage to the central and peripheral parts of the regulation of testosterone synthesis.

Chronic exposure to tire rubber-derived contaminant 6PPD-quinone impairs sperm quality and induces the damage of reproductive capacity in male mice

It has been reported that N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q), a derivative of the tire antioxidant, N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD), exhibits acute toxicity towards organisms. However, the possible reproductive toxicity of 6PPD-Q in mammals has rarely been reported. In this study, the effects of 6PPD-Q on the reproductive toxicity of C57Bl/6 male mice were assessed after exposure to 6PPD-Q for 40 days at 4 mg/kg body weight (bw). Exposure to 6PPD-Q not only led to a decrease in testosterone levels but also adversely affected semen quality and in vitro fertilization (IVF) outcomes, thereby indicating impaired male fertility resulting from 6PPD-Q exposure. Additionally, transcriptomic and metabolomic analyses revealed that 6PPD-Q elicited differential expression of genes and metabolites primarily enriched in spermatogenesis, apoptosis, arginine biosynthesis, and sphingolipid metabolism in the testes of mice. In conclusion, our study reveals the toxicity of 6PPD-Q on the reproductive capacity concerning baseline endocrine disorders, sperm quality, germ cell apoptosis, and the sphingolipid signaling pathway in mice. These findings contribute to an enhanced understanding of the health hazards posed by 6PPD-Q to mammals, thereby facilitating the development of more robust safety regulations governing the utilization and disposal of rubber products.

Dysbiosis of Gut Microbiome Aggravated Male Infertility in Captivity of Plateau Pika.

Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial α-diversity and Firmicutes/Bacteroidetes ratio were drastically decreased in the captivity group. Bacteroidetes and Muribaculaceae abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites' short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between Gastranaerophilales family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.

Determination of M1/M2 Macrophage Polarization in Ipsilateral and Contralateral Rat Testis Tissue Following Unilateral Torsion/Detorsion.

The present study investigates the changes in M1/M2 macrophage polarization resulting from unilateral testicular torsion in the bilateral testis. The study sample included 63 male Sprague-Dawley rats, which were randomly divided into nine groups (n = 7): Control, Sham (4h (4h), 24h, 7days (7d), 14d), and Torsion/Detorsion (T/D) (4h, 24h, 7d, 14d). Histopathological evaluations revealed no changes in the Sham groups, while T/D was noted to cause edema, vascular occlusion, disruption of seminiferous tubule epithelial organization, germ cell abnormalities and structural anomalies in the experimental rats, the severity and extent of which increased from 4h to 14d after T/D. The Cosentino scores used to determine the degree of histological damage were consistent with the histopathological findings in all groups, while the Johnsen scores, as a marker of spermatogenesis, were lower in the T/D groups. Seminiferous tubule diameters and germinal epithelial thickness decreased significantly in parallel with increased tubule damage in the ipsilateral testicles. Testicular torsion significantly affected sperm motility, with significant reductions observed in the T/D 7d and T/D 14d groups. A hormone profile analysis revealed decreased testosterone levels in both the Sham and T/D groups when compared to the Controls. CD68 and CD163 immunoreactivities, as M1 and M2 macrophage surface markers, were determined in the testicular tissue using the avidin-biotin-peroxidase complex method. T/D interventions caused M1/M2 macrophage polarization changes and increased M1 macrophages, particularly in contralateral testicular tissue. The increase in M1 macrophages in contralateral testicular tissue following T/D in the present study suggests that cell processes, including macrophages, may play an important role in contralateral testicular injury.

Molecular Regulatory Mechanism of Nano-Se Against Copper-Induced Spermatogenesis Disorder.

Selenium nanoparticle (Nano-Se) is a new type of selenium supplement, which can improve the deficiency of traditional selenium supplements and maintain its physiological activity. Due to industrial pollution and irrational use in agriculture, Cu overexposure often occurs in animals and humans. In this study, Nano-Se alleviated CuSO4-induced testicular Cu accumulation, serum testosterone level decrease, testicular structural damage, and decrease in sperm quality. Meanwhile, Nano-Se reduced the ROS content in mice testis and enhanced the activities of T-AOC, GSH, SOD, and CAT compared with CuSO4 group. Furthermore, Nano-Se alleviated CuSO4-induced apoptosis by increasing the protein expression of Cleaved-Caspase-3, Cleaved-Caspase-9, Cleaved-Caspase-12, and Bax/Bcl-2 compared with CuSO4 group. At the same time, Nano-Se reversed CuSO4-induced increase of γ-H2AX protein expression in mice testis. In conclusion, this study confirmed that Nano-Se could alleviate oxidative stress, apoptosis, and DNA damage in the testis of mice with Cu excess, thereby protecting the spermatogenesis disorder induced by Cu.

Congenital Zika virus infection impacts on male mouse offspring's reproductive biology.

Congenital ZIKV infection promotes alarming effects on male offspring's reproductive biology. This study showed the presence of the ZIKV antigen in the testis parenchyma, decreased testosterone levels, and sperm abnormalities in male offspring born to infected mothers. Infection with ZIKV during pregnancy is associated with fetal developmental problems. Although neurological issues are being explored more in experimental studies, limited research has focused on the reproductive health consequences for offspring born to infected mothers. In this context, this study aimed to assess the impact of ZIKV infection during pregnancy on the testes and sperm of adult male offspring. Female mice were intraperitoneally inoculated with a Brazil strain of ZIKV during the 5.5th day of embryonic gestation. The offspring were evaluated 12 weeks after birth to analyze cellular and molecular changes in the testes and sperm. A novel approach combining variable-angle spectroscopic ellipsometry and machine learning modeling was also introduced for sperm sample analysis. The study revealed the presence of ZIKV protein in the testis parenchyma of adult male offspring born to infected mothers. It was shown that the testes exhibited altered steroidogenesis and inflammatory mediators, in addition to significant issues with spermiogenesis that resulted in sperm with DNA fragmentation, head defects, and protamination failure. Additionally, sperm dielectric properties and artificial intelligence showed potential for rapid identification and classification of sperm samples from infected mice. These findings provide crucial insights into the reproductive risks for men born from ZIKV-infected pregnant women.