Decreased Serum Testosterone Levels Research Articles

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.

Serum testosterone levels and oxidative stress in type 1 diabetes, type 2 diabetes, and obesity.

Obesity, type 1 diabetes mellitus (T1DM), and type 2 diabetes mellitus (T2DM) are metabolic diseases that continue to be a global problem. Testosterone levels in men are affected by several factors, including obesity and DM. Although the relationship between diabetes and testosterone is not fully understood, oxidative stress is thought to play a major role. The aim of this study was to compare serum testosterone levels and oxidative stress markers [total antioxidant status (TAS), total oxidant capacity (TOS), oxidative stress index (OSI), and ischaemic modified albumin (IMA)] among the control group and experimentally induced obese, T1DM, and T2DM rats. The study included 28 male Sprague-Dawley rats divided into 4 groups: the obesity group were fed a high-fat diet (HFD), the T2DM group received a HFD plus a single dose of streptozocin (STZ), the T1DM group received only STZ, and there was a control group. Serum testosterone, TAS, TOS, OSI, and IMA were analysed. Serum testosterone levels were lower in the T1DM and T2DM groups compared to the control and obesity groups. The TOS levels were highest in the T2DM group, followed by the T1DM group, the obesity group, and finally the control group. No significant difference was found between the obesity group and the control group in terms of TOS levels. Regarding TAS levels, the order observed was control group > obesity group > T2DM > T1DM. Testosterone was positively correlated with TAS and negatively correlated with TOS and OSI. Increased oxidative stress in diabetes may be an important factor that decreases serum testosterone levels.

Male Menopause: Concept Challenges and Coping Strategies

Men’s health is globally in crisis and worsening due to limited healthcare policies, and under-developed societal awareness and education. Men frequently realize reproductive health services as being meant for females because of this they do not see a place for themselves in those services. Male menopause, or more accurately, testosterone deficiency syndrome (TDS) is one of the new issues which can affect the quality of life in older men. It is a natural phenomenon that occurs with age in men and is diagnosed by clinical manifestation and a decrease in serum testosterone levels; it affects the performance of many systems of the body from the head to toe. Moreover, age-related comorbid diseases such as diabetes, heart disease, renal disease, obesity, metabolic syndrome, and some medications such as glucocorticoids, cigarettes and alcohol also contribute to the decline in testosterone levels. There are numerous challenges faced by men in Africa during the climacteric period and they are accentuated by several intermediating factors which range from ignorance, to cultural taboos and even lack of adequate facilities to cater for their health needs. If these middle-aged men continue to experience the challenges of male menopause without effective coping strategies, their quality of life is at stake. This paper therefore stresses challenges of male menopause and recommends lifestyle changes, healthy emotion focused coping strategies and other relaxation techniques to improve the quality of life of elderly men experiencing male menopause.

Long noncoding RNA XIST inhibition promotes Leydig cell apoptosis by acting as a competing endogenous RNA for microRNA-145a-5p that targets SIRT1 in late-onset hypogonadism.

Leydig cell (LCs) apoptosis is responsible for decreased serum testosterone levels during late-onset hypogonadism (LOH). Our study was designed to illustrate the regulatory effect of lncRNA XIST on LCs and to clarify its molecular mechanism of action in LOH. The Leydig cells (TM3) was treated by 300μM H2O2 for 8h to establish Leydig cell oxidative stress model in vitro. The expression levels of lncRNA XIST in the testicular tissues of patients with LOH were measured using fluorescence in situ hybridization (FISH). The interaction between lncRNA XIST/SIRT1 and miR-145a-5p was assessed using starBase and dual-luciferase reporter gene assays. Apoptotic cells and Caspase3 activity were determined by flow cytometry (FCM) assay. Testosterone concentration was determined by ELISA. Moreover, histological assessment of testicles in mice was performed by using HE staining and the TUNEL assay was used to determine apoptosis. We found that the lncRNA XIST was downregulated in the testicular tissues of LOH patients and mice and in H2O2-induced TM3 cells. XIST siRNA significantly promoted apoptosis, enhanced Caspase3 activity and reduced testosterone levels in H2O2-stimulated TM3 cells. Further studies showed that the miR-145a-5p inhibitor reversed the effect of XIST-siRNA on H2O2-induced Leydig cell apoptosis. MiR-145a-5p negatively regulated SIRT1 expression, and SIRT1-siRNA reversed the effects of the miR-145a-5p inhibitor on H2O2 stimulated TM3 cells. The in vivo experiments indicated that silencing of the lncRNA XIST aggravated LOH symptoms in mice. Inhibition of lncRNA XIST induces Leydig cell apoptosis through the miR-145a-5p/SIRT1 axis in the progression of LOH.

Effects of the adsorption behavior of polyamide microplastics on male reproductive health by reduction of testosterone bioavailability

Microplastics (MPs) are global environmental pollutants with potential toxicity concerns, and their effects on the reproductive system have attracted increasing attention. This study investigated the interaction between MPs and mammalian biomolecules, focusing on the relationship between the testosterone adsorption behavior of MPs and male reproductive health. The adsorption capacity of different types of MPs for testosterone was evaluated in vitro experiments. Polyamide (PA)-MPs exhibited stronger adsorption, while polymethyl methacrylate (PMMA)-MPs displayed the weakest adsorption. Sorption equilibrium between PA-MPs and testosterone was achieved within 6 h, fitting the Pseudo-2nd-order model and Langmuir isotherm. The effects of MPs on male reproduction in mice was determined in vivo experiments. Male mice were treated with 0.1 and 0.5 mg/d PA-MPs/PMMA-MPs by gavage once per day for 28 days. The results showed that only 0.5 mg/d PA-MP exposure induced decreased serum testosterone levels, increased testicular testosterone levels compared to the control, and more severe damage to seminiferous tubule structure, sperm motility and sperm morphology compared to the PMMA-MPs group. Meanwhile, PA-MPs could reduce intracellular nuclear translocation of androgen receptor (AR) mediated by testosterone, while PMMA-MPs had no impact. The study revealed that PA-MP adsorption reduced testosterone bioavailability and caused sperm quality to decline, offering new insights into the combined toxicity mechanism of MPs in male mammals.

Curcumin-loaded chitosan-protamine nanoparticles: A promising approach to ameliorate nicotine-induced reproductive disorders in male rats

Nicotine (NIC) exposure has been shown to impair male fertility, affecting sperm quality and motility. Curcumin (CUR) has been shown to have anti-inflammatory and antioxidant properties and has demonstrated potential in treating a range of health conditions, including infertility. The current study aimed to investigate the effects of curcumin encapsulated in chitosan-protamine nanoparticles (CUR-CPNPs) against nicotine-induced reproductive dysfunction in male rats. CUR-CPNPs were chemically prepared and characterized by TEM imaging, Zetasizer, and FT-IR spectroscopy. eight groups (6 rats per each) of male rats were used: first & second groups acted as control, third group received CUR-CPNPs (250 mg/kg), fourth group received CUR (250 mg/kg), fifth group received CPNPs (250 mg/kg), sixth group received 0.6 mg/kg nicotine (NIC). Finally, seventh and eighth groups are received NIC + CUR, NIC + CUR-CPNPs, respectively. After the end of the treatment period, the rats were anesthetized then the relative weight of the reproductive organs, semen analysis, testosterone levels and oxidative stress biomarkers were assessed, and finally a histopathological analysis of the testicular tissue was performed.The impacts of NIC administration resulted in a significant reduction in relative reproductive organs weights, exacerbated oxidative stress, decreased serum testosterone level, and negatively impacted semen count, motility, and viability. Testicular histopathology revealed extensive degenerative alterations. On the other hand, the ameliorative role of CUR-CPNPs clearly reversed the devastating effect caused by nicotine.

Association of Extracelluar Matrix Protien 1 with Semen Parameters and Testosterone Concentration in Male Infertility

Background: Extracellular matrix protein 1 (ECM1) is a glycoprotein that interacts with extracellular proteins into semen predominantly by epididymis, supports considering the role of the epididymis in sperm maturation. Testosterone is a steroid hormone from the androgen group is primarily secreted in the testes. Objectives: The aim of this study is to assess the concentration of ECM1 and serum by (ELISA) kit with semen parameters in fertile and infertile men in Najaf City, Iraq. Material and Methods: A total of 90 participants (45 infertile and 45 fertile men) were mean age (40.02) control fertility male, while the mean age as infertile (40.22) years included in the current study. The patients were sub-grouped into: 45 infertile with semen abnormal oligozoospermia, azoospermia, asthenozoospermia and teratozoospermia patients, it used for measuring the concentration and parameters ECM1and serum testosterone by Elisa kit. Results: Statistical analysis showed highly significant differences between the two groups show (p < 0.05). The level of ECM in the infertile group was lower in concentration than the control group with statistically significant differences (p < 0.0001*). The difference between the totals was highly significant by a criterion (p < 0.0001*) 45 in all group that studied a positive person correlation highly significant between serum testosterone (IU/mL) and seminal ECM1, (pg/mL) in all age groups of 45 male infertility at a (p < 0.001*). Conclusion: The decrease in serum testosterone levels with the decrease in the level of seminal plasma ECM1 in infertile men provide evidence that levels can be used as reliable markers in the diagnostic criteria of male infertility. This study’s results suggest that concentration ECM1.

Nickel-induced oxidative stress causes cell death in testicles: implications for male infertility.

Aligarh region is well known for its lock industry. This lock industry utilises nickel for electroplating. There have been informal reports of infertility in men and women living near the lock industry. We analysed field water samples to investigate this link, and the results showed considerable nickel contamination. To further validate our results, we exposed male rats to relevant nickel levels in drinking water. This experimental exposure resulted in abnormal sperm morphology, decline in sperm count, significant change in activities of antioxidant enzymes, pronounced oxidative stress in the rat spermatocytes and decrease in serum testosterone level, as well as damage in the hypothalamus and pituitary (in all cases, the changes were most significant at the highest concentration used i.e 2.5 mg/l). The breeding experiments showed decline in live birth rate, while pups did not survive post birth in cages where males were given 2 and 2.5 mg/l concentrations of nickel in drinking water prior to mating. Our data strongly indicate a link between industrial nickel exposure and male infertility.

Knockdown of ZnT4 Induced Apoptosis, Inhibited Proliferation and testosterone synthesis of TM3 cells.

Zinc deficiency has a huge impact on male reproduction. The zinc transporter (ZnT) family is involved in the maintenance of zinc homeostasis and testosterone synthesis. However, the underlying mechanisms remain to be investigated. Therefore, in this study, we aimed to determine the effect of zinc transporter 4 (ZnT4) on testosterone synthesis in male Kunming mice and mouse Leydig cells. The results of this study showed that compared with the zinc normal diet group (Con group), the zinc-deficient diet group (ZnD group) had decreased zinc content and increased ZnT4 expression in testicular tissues, and decreased serum testosterone levels, suggesting that ZnT4 may be involved in Leydig cell injury resulting from a zinc-deficient diet. Subsequently, mouse Leydig cell line TM3 cells were used to analyze the effect of ZnT4 downregulation on TM3 cell proliferation and apoptosis, on testosterone synthesis, and its underlying mechanisms. Here, we show that knockdown of ZnT4 can induce the accumulation of zinc, inhibit the viability, and induce apoptosis in TM3 cells. In addition, knockdown of ZnT4 downregulated testosterone concentration and expression of testosterone synthesis-related proteins steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) in TM3 cells, while hCG could rescue their levels. We show that it is ZnT4 that plays a role in testosterone production through a mediated PI3K/Akt/mTOR autophagy pathway, whereas mTORC1 complex inhibitor (Rapa) blocks the decrease in testosterone levels caused by ZnT4 downregulation. In conclusion, the above results indicate that ZnT4 plays an important role in regulating testosterone synthesis.

Endocrine disrupting chemicals and their effects on the reproductive health in men

Endocrine Disrupting Chemicals (EDCs) are harmful compounds that enter the environment naturally or through anthropogenic activities and disrupt normal endocrine functions in humans, adversely affecting reproductive health. Among the most significant sources of EDC contaminants are the pharmaceutical, cosmetic, and packaging industries. EDCs have been identified to have a deteriorating effect on male reproductive system, as evidenced by the increasing number of male infertility cases. A large number of case studies have been published in which men exposed to EDCs experienced testicular cancer, undescended testicles, a decrease in serum testosterone levels, and poor semen quality. Furthermore, epidemiological evidence suggested a link between prenatal EDC exposure and cryptorchidism or undescended testicles, hypospadias, and decreased anogenital distance in infants. The majority of these findings, however, are incongruent due to the lack of long-term follow-up studies that would demonstrate EDCs to be associated with male reproductive disorders. This review aims to provide an overview on recent scientific progress on the association of EDCs to male reproductive health with special emphasis on its toxicity and possible mechanism of EDCs that disrupt male reproductive system.

Cardiovascular comorbidities and cardiovascular events in patients with metastatic prostate cancer.

e18851 Background: Prostate cancer (PCa) is globally the second most frequently diagnosed cancer in men. Patients with metastatic disease require cancer treatment for several months or even years. These treatments can have different side effects including adverse cardiac effects because of decreased serum testosterone levels. Methods: We conducted an observational study of men who were diagnosed with metastatic PCa from January 1, 2013, through December 31, 2018, with follow-up through December 31, 2022. We documented comorbid conditions, medications, tumor characteristics, type and duration of systemic treatment received. We also documented fasting glucose, total cholesterol, HDL, LDL and triglyceride levels at diagnosis. A cardiovascular event was defined as the first occurrence of hypertension, myocardial infraction, atrial fibrillation, heart failure, sudden cardiac death, acute thrombo-embolism and stroke. Cox proportional hazards models were used to assess association between cancer treatment and incident cardiovascular disease (CVD). Results: The cohort included One hundred and twenty one men who were diagnosed with metastatic prostate adenocarcinoma with a mean age at diagnosis of 68.9 years. 84.2% had bone-only metastasis. 69.4% had at least one CVD-Risk Factor. 53.4% Hypertension, 28.2% Dyslipidemia, 12.3% Diabetes. 15 men (12.3%) had pre-existing CVD. 3.3% stroke, 4.1% myocardial infraction, 2.4% heart failure, 2.4% atrial fibrillaton. 24.2% were under statin therapy and 22.0% under aspirin. Androgen deprivation therapy (ADT) was used for all patients, including 9.9% goserelin, 3.3% leuprolide and 86.8 triptorelin. 70.2 % had received concomitant treatment: 22.3% bicalutamide, 60.3% abiraterone, 68.8% docetaxel, 4.1% cabazitaxel. Men were observed for a median of 5.6 years (range = 33 days to 10 years). Cardiovascular adverse events occurred in 14 patients (11.5%) on ADT alone and in 23 (19.0%) on combination therapy. 26 (21.4%) Hypertension, 1 (0.8%) myocardial infraction, 1 (0.8%) atrial fibrillation, 2 (1.6%) had heart failure, 1 (0.8%) sudden cardiac death, 5 (4.1%) acute thrombo-embolism, 1 (0.8%) stroke. In subgroup-analyses of different combination treatments, Cardiovascular events were found to be significantly associated with combination of abiraterone with ADT (HR = 1.31, 95 % CI: 1.13 to 1.37; P < 0.001). For men with a history of pre-existing CVD, CV events were more pronounced, 23.9% vs. 6.6% for men without pre-existing CVD. Conclusions: Metastatic prostate cancer patients often have pre-existing CVD and CVD-Risk Factors. Addition of abiraterone to ADT increase the risk of cardiovascular events. Physicians should monitor their patients in order to early detect any abnormality, and should encourage them to adopt a healthier lifestyle.

The Effects of Glutathione on Clinically Essential Fertility Parameters in a Bleomycin Etoposide Cisplatin Chemotherapy Model.

Chemotherapeutic agents used in the treatment of testicular cancer cause damage to healthy tissues, including the testis. We investigated the effects of glutathione on sperm DNA integrity and testicular histomorphology in bleomycin etoposide cisplatin (BEP) treated rats. Twelve-week-old male rats of reproductive age (n = 24) were randomly divided into three groups, the (i) control group, (ii) BEP group, and (iii) BEP+ glutathione group. Weight gain increase and testes indices of the control group were found to be higher than that of the BEP group and BEP+ glutathione group. While the BEP treatment increased sperm DNA fragmentation and morphological abnormalities when compared to the control group, GSH treatment resulted in a marked decrease for both parameters. Moreover, BEP treatment significantly decreased serum testosterone levels and sperm counts in comparison to the control group, yet this reduction was recovered in the BEP+ glutathione treated group. Similarly, seminiferous tubule epithelial thicknesses and Johnsen scores in testicles were higher in the control and BEP+ glutathione groups than in the BEP-treated group. In conclusion, exogenous glutathione might prevent the deterioration of male reproductive functions by alleviating the detrimental effects of BEP treatment on sperm quality and testicular histomorphology.

Citrinin inhibits the function of Leydig cells in male rats in prepuberty

Citrinin, a mycotoxin existing in fruits, has nephrotoxicity, hepatotoxicity and embryotoxicity. The effects of citrinin on Leydig cell development in prepuberty remains unclear. Male Sprague-Dawley rats were gavaged with 0, 1, 2.5, and 5 mg/kg citrinin from postnatal days 21–28. Citrinin at 5 mg/kg significantly decreased serum testosterone levels, while increasing serum LH and FSH levels. Citrinin at 1–5 mg/kg markedly downregulated Hsd17b3 and HSD17B3 expression, while upregulating Srd5a1 (SRD5A1) and Akr1c14 (AKR1C14) expression at 2.5 and/or 5 mg/kg. Citrinin at 5 mg/kg also significantly increased PCNA-labeling index in Leydig cells. Citrinin at 5 mg/kg significantly raised testicular MDA amount, whiling at 2.5 and 5 mg/kg downregulating SOD1 and SOD2 expression. Citrinin at 5 mg/kg markedly decreased the ratio of Bcl2 to Bax, in consistent with the increased apoptosis in Leydig cells judged by TUNEL assay. Enzymatic assay revealed that citrinin inhibited rat testicular HSD3B1 activity at 100 µM and HSD17B3 activity at 10–100 μM. Citrinin at 50 μM and higher also induced reactive oxygen species (ROS) and apoptosis of R2C cell line. In conclusion, citrinin inhibits Leydig cell development at multiple levels via different mechanisms and oxidative stress partially plays a role.

Cisplatin-induced azoospermia and testicular damage ameliorated by adipose-derived mesenchymal stem cells

BackgroundThe testes are highly susceptible to the adverse effects of chemotherapy and radiation at all stages of life. Exposure to these threats mainly occurs during cancer treatment and as an occupational hazard in radiation centers. The present study investigated the regenerative ability of adipose-derived mesenchymal stem cells (ADMSCs) against the adverse effects of cisplatin on the structure and function of the testes.MethodsNew Zealand white rabbits (N = 15) were divided into three groups of five: a negative control group (no treatment), a cisplatin group (single dose of cisplatin into each testis followed three days later by a PBS injection), and a cisplatin + ADMSCs group (cisplatin injection followed three days later by an ADMSC injection). On day 45 post-treatment, serum testosterone levels were evaluated, and the testes and epididymis were collected for histology, oxidative stress examination, and epididymal sperm analysis.ResultsCisplatin caused damage to the testicular tissue and decreased serum testosterone levels, epididymal sperm counts, and oxidants. An antioxidant imbalance was detected due to increasing malondialdehyde (MDA) and reduced glutathione (GSH) levels in testicular tissue. The ADMSC-treated group displayed a moderate epididymal sperm count, adequate antioxidant protection, suitable hormone levels, and enhanced testicular tissue morphology.ConclusionsADMSCs treatment repaired damaged testicular tissue, enhanced biochemical parameters, and modified pathological changes caused by cisplatin.

Derivation of benchmark doses for male reproductive toxicity in a subacute low-level Pb exposure model in rats

The objectives of the study were to simulate low-level Pb exposure scenario in an animal model and to examine reproductive adverse effects. Based on obtained data, we have performed Benchmark dose (BMD)-response modelling. Male Wistar rats were randomized in seven groups (n = 6): one control and six treated with: 0.1, 0.5, 1, 3, 7, and 15 mg Pb/kg body weight, daily for 28 days by oral gavage. The rats were sacrificed and the blood and testes were used for further analysis of testosterone levels in serum, testicular essential metal levels and histological analysis. The Pb treatment led to a dose-dependent decrease of serum testosterone levels with a negative trend (BMDI 0.17–6.13 mg Pb/kg). Increase of Zn (dose-dependent, BMDI 0.004–19.7 mg Pb/kg) and Cu and a decrease of Mn testicular levels were also detected with unscathed histology of the testes. The presented results might be used in further evaluation of the point of departure in human health risk assessment for Pb.

Attenuation Effect of Recovery Sleep for Impaired Reproductive Function in Male Rats by Sleep Deprivation.

The aim of the present study was to test the hypothesis that recovery sleep could counteract the detrimental effects of sleep deprivation (SD) on male rats' fertility. Twenty-two rats were housed in groups of six per cage with unrestricted access to food and water in a room. The modified multiple platform method was used to induce SD in rats over a 96-hour period. We examined the effect of SD on semen quality, reproductive hormones, and testicular histology in adult male rats. Then, we investigated the effect of 7 days recovery sleep on impaired reproductive function induced by SD. After the acclimation period, 22 rats were randomly separated into three experimental groups (SD, recovery sleep, and the control groups). Ninety-six hours of SD resulted in a significant decrease in sperm motility (24.33±10.93 vs. 48.20±8.55, p<0.001) and the number of morphologically normal sperm (9.68±2.77 vs. 26.21±14.60, p<0.01) in rats, accompanied by a decrease in testosterone levels (1.53±0.55 vs. 4.44±0.56, p<0.001) and destruction of testicular tissue structure compared with control group. After 7 days of recovery sleep, semen quality, especially sperm motility, was improved and testosterone levels were significantly higher compared to post-SD (3.70±0.53 vs. 1.53±0.55, p<0.05), but remained low compared to the control group. In conclusion, 96 hours of SD deteriorated the parameters of sperm motility and the number of morphologically normal sperm in rats, probably due to the decrease in serum testosterone levels and the disruption of testicular tissue structure when compared to the control group. After 7 days of recovery sleep, semen parameter, especially sperm motility and testosterone levels did not return to baseline levels compared to the control group.

Stress-related testicular changes in Wistar and Sprague-Dawley rats following oral administration of an interleukin-8 inhibitor

We describe testicular changes in Wistar and Sprague-Dawley rats following oral administration of DF2156A, a novel allosteric inhibitor of the CXCR1/CXCR2 receptors of interleukin-8. These testicular changes, which were associated with clinical signs, modifications of body weight parameters (decrease of body weight and weight gain) and a decrease of testosterone serum levels, were not considered to be a direct toxic effect of the test substance but secondary to a likely induced stress resulting from the oral administration of a high dose (200 mg/kg/day) of the test substance to male rats for a period of six weeks. Testicular changes consisted of seminiferous tubules atrophy and germinal cell degeneration and only occurred in animals presenting clinical signs of transient visible weight loss, ruffled fur and/or weakened condition, and/or decreased body weight and weight gain. A decrease in serum testosterone levels was only observed in those Sprague-Dawley rats affected by decreased body weight, weight gain and testicular changes. Only a single Wistar rat with testicular changes exhibited relevant reduced levels of circulating testosterone. Sperm analysis in terms of motility, morphology and number of sperm cells was altered in males presenting with morphological changes in the testes. Sprague-Dawley rats with testicular changes were more numerous and with more pronounced lesions than were Wistar rats.

МОРФОФУНКЦИОНАЛЬНЫЕ ИЗМЕНЕНИЯ СЕМЕННИКОВ КРЫСПРИ ПРЕЖДЕВРЕМЕННОМ СТАРЕНИИ, ВЫЗВАННОМ ТЕМНОВОЙ ДЕПРИВАЦИЕЙ

The rapid development of technology has a significant impact on the daily life of a person. Light, sound, information pollution leads to sleep disturbance, which has a negative impact on the physical condition. Even short-term sleep disturbance caused by dark deprivation leads to a decrease in serum testosterone levels. The imbalance of male sex hormones, the synthesis of which is under the control of the hypothalamic-pituitary system, negatively affects the morphofunctional state of the testes. The effect of exogenous melatonin on the morphological and functional state of the spermatogenic epithelium of the testes, Leydig cells in white outbred male rats of 4 months of age was studied on the model of premature aging caused by 30-day dark deprivation, and the Klotho protein level in blood serum was assessed by enzyme immunoassay. It was found that the morphological changes in the testes were characterized by a decrease in the thickness of the spermatogenic epithelium by 30 days after darkdeprivation and a decrease in the level of the Klotho protein, which is a marker of premature aging. The introduction of exogenous melatonin had a protective effect on the morphological and functional status of the testes of animals, accompanied by the restorationof the spermatogenic epithelium, an increase in the Klotho protein to the level of thenegative control group

Dopamine D2 receptors in the dorsomedial prefrontal cortex modulate social hierarchy in male mice.

Social hierarchy greatly influences behavior and health. Both human and animal studies have signaled the medial prefrontal cortex (mPFC) as specifically related to social hierarchy. Dopamine D1 receptors (D1Rs) and D2 receptors (D2Rs) are abundantly expressed in the mPFC, modulating its functions. However, it is unclear how DR-expressing neurons in the mPFC regulate social hierarchy. Here, using a confrontation tube test, we found that most adult C57BL/6J male mice could establish a linear social rank after 1 week of cohabitation. Lower rank individuals showed social anxiety together with decreased serum testosterone levels. D2R expression was significantly downregulated in the dorsal part of mPFC (dmPFC) in lower rank individuals, whereas D1R expression showed no significant difference among the rank groups in the whole mPFC. Virus knockdown of D2Rs in the dmPFC led to mice being particularly prone to lose the contests in the confrontation tube test. Finally, simultaneous D2R activation in the subordinates and D2R inhibition in the dominants in a pair switched their dominant-subordinate relationship. The above results indicate that D2Rs in the dmPFC play an important role in social dominance. Our findings provide novel insights into the divergent functions of prefrontal D1Rs and D2Rs in social dominance, which may contribute to ameliorating social dysfunctions along with abnormal social hierarchy.

Identification of endocrine-disrupting chemicals targeting the genes and pathways of genital anomalies in males

Hypospadias and cryptorchidism are the most common congenital malformations in male neonates, both of which are also the important clinical manifestations of testicular dysgenesis syndrome and share a same origin. Many studies have suggested that prenatal exposure to endocrine-disrupting chemicals (EDCs) is associated with hypospadias and cryptorchidism development. However, the consistent mechanisms remain unclear. To identify the key EDCs, genes and biological networks related to the development of hypospadias and cryptorchidism respectively and commonly, we conduct the present study and found a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals. Transcriptome profiles were obtained from the Comparative Toxicogenomics Database (CTD). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses and protein-protein interaction (PPI) network were applied for integrative analyses. The rat model and molecular docking were applied to furtherly verifying the findings of the integrative analyses. Besides the highly related genes, most enriched pathways and chemicals for hypospadias and cryptorchidism respectively, we found hypospadias and cryptorchidism share many same highly associated EDCs (e.g., dibutyl phthalate) and genes (e.g., androgen receptor and estrogen receptor 1) through comparing highly related chemicals or genes of hypospadias and cryptorchidism respectively. GO and KEGG analysis showed that these same interactive genes were mainly enriched in steroidogenesis, response to steroid hormone and nuclear receptor activity. PPI network analysis identified 15 biological hub genes. Furtherly, hypospadias and cryptorchidism were induced by prenatal dibutyl phthalate exposure. Decreased serum testosterone level, downregulation of nuclear androgen-dependent and upregulation of cytoplasmic estrogen-dependent pathways may lead to hypospadias and cryptorchidism. This study proposed a new method for predicting the correlation between the interactive genes of hypospadias/cryptorchidism and chemicals and found that hypospadias and cryptorchidism share many same highly associated EDCs and genes.