Decreased Serum Testosterone Research Articles

Effects of pharmacological doses of niacin on subacute glucocorticoid-induced testicular damage in rats.

Glucocorticoid excess adversely affects male reproduction. This study evaluates effects of pharmacological doses of niacin on testicular structure and function in dexamethasone-treated rats. Adult rats (48) were randomly assigned to 6 equal groups: (1) Negative control (NC): normal rats; (2) Positive control (PC): dexamethasone at 7 mg/kg/day by intraperitoneal injections for 7 days; groups 3-6 (N50, N100, N200, and N400): dexamethasone and concomitant treatment with niacin at 50, 100, 200, and 400 mg/kg/day by oral gavages. Testicular weight and volume of PC rats were significantly lower than the NC group (p < .05). Testicular volume of rats in the N50 and N200 groups was statistically similar to the NC group. Significant decreases in serum testosterone with a slight LH increase were detected in the PC group. Nacin at 50 mg/kg reversed serum testosterone to NC levels and increased serum LH concentration. Niacin only slightly increased epididymal spermatozoa number while all groups of niacin-treated rats had significantly higher percentages of motile spermatozoa compared with the PC group. Hypospermatogenesis, germ cell degeneration and depletion, epithelial vacuolization, and degenerated Leydig cells were observed in PC rats. Lesions were relatively milder in niacin-treated rats. Johnsen scores were also significantly higher in niacin-treated rats. Niacin reduced apoptosis as shown by TUNEL assay. In conclusion, niacin administration at pharmacological doses dose-dependently ameliorates the destructive effects of dexamethasone on sperm motility, Johnsen score, and testicular cell apoptosis in rats with the latter can be considered a decisive mechanism for its positive effects on testis.

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 &lt; 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.

Evidence of the protective role of D-Aspartate in counteracting/preventing cadmium-induced oxidative stress in the rat testis

Cadmium (Cd), by producing oxidative stress and acting as an endocrine disruptor, is known to cause severe testicular injury, documented by histological and biomolecular alterations, such as decreased serum testosterone (T) level and impairment of spermatogenesis. This is the first report on the potential counteractive/preventive action of D-Aspartate (D-Asp), a well-known stimulator of T biosynthesis and spermatogenesis progression by affecting hypothalamic-pituitary-gonadal axis, in alleviating Cd effects in the rat testis. Our results confirmed that Cd affects testicular activity, as documented by the reduction of serum T concentration and of the protein levels of steroidogenesis (StAR, 3β-HSD, and 17β-HSD) and spermatogenesis (PCNA, p-H3, and SYCP3) markers. Moreover, higher protein levels of cytochrome C and caspase 3, together with the number of cells positive to TUNEL assay, indicated the intensification of the apoptotic process. D-Asp administered either simultaneously to Cd, or for 15 days before the Cd-treatment, reduced the oxidative stress induced by the metal, alleviating the consequent harmful effects. Interestingly, the preventive action of D-Asp was more effective than its counteractive effect. A possible explanation is that giving D-Asp for 15 days induces its significant uptake in the testes, reaching the concentrations necessary for optimum function. In summary, this report highlights, for the first time, the beneficial role played by D-Asp in both counteracting/preventing the adverse Cd effects in the rat testis, strongly encouraging further investigations to consider the potential value of D-Asp also in improving human testicular health and male fertility.

Testosterone propionate and Swarna Bhasma treatment modulated D-galactose induced reproductive alterations in male Wistar rats: An experimental study.

The male reproductive system undergoes several adverse age-related changes like decreased hormone synthesis, sperm count, and testicular alteration that can impact on fertility. The study aims to investigate the effects of testosterone propionate (TP), and ayurvedic formulation Swarna Bhasma (SB) on D-galactose (D-gal) induced reproductive aging in male Wistar rats. 60 male Wistar rats were divided into 10 groups of 6 animals. Reproductive aging was induced by D-gal (150 mg/kg Bwt) exposure for 60 days. The rats were then treated by post and combination treatment with TP (2 mg/kg Bwt) and SB (6.75 mg/kg Bwt). Then sperm parameters, reproductive hormones, inflammatory markers, testicular antioxidant enzymes, steroidogenic enzymes, and histological manifestation of testis were evaluated. Exposure of D-gal caused significant (p 0.001) decrease in serum testosterone (T), testicular steroidogenic, and antioxidant enzymes. Administration of TP increased the serum T level, testicular antioxidant enzymes, and spermatogenic profile at a significant level of (p 0.001) compared to D-gal. Further, the SB treatment significantly (p 0.001) elevated the serum T level, sperm count, testicular antioxidant enzymes, steroidogenic enzymes, when compared to D-gal. Both the treatment of TP and SB treatments recovered the reproductive impairments caused by D-gal. However, exogenous T supplementation via TP administration is associated with various side effects during long-term use. SB is an Ayurvedic formulation having a long history of usage in India. The current findings suggest that the SB may be used as a good alternative for potentiating reproductive function in aging males.

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.

Green Synthesized Zinc Oxide Nanoparticles Using Moringa olifera Ethanolic Extract Lessens Acrylamide-Induced Testicular Damage, Apoptosis, and Steroidogenesis-Related Gene Dysregulation in Adult Rats

This study assessed the possible protective role of green synthesized zinc oxide nanoparticles using Moringa olifera leaf extract (MO-ZNPs) in acrylamide (ACR)-induced reproductive dysfunctions in male rats. ACR (20 mg/kg b.wt/day) and/or MO-ZNPs (10 mg/kg b.wt/day) were given orally by gastric gavage for 60 days. Then, sperm parameters; testicular enzymes; oxidative stress markers; reproductive hormones including testosterone, luteinizing hormone (LH)-estradiol, and follicle-stimulating hormone (FSH) concentration; testis histology; steroidogenesis-related gene expression; and apoptotic markers were examined. The findings revealed that MO-ZNPs significantly ameliorated the ACR-induced decline in the gonadosomatic index and altered the pituitary-gonadal axis, reflected by decreased serum testosterone and FSH with increased estradiol and LH, and sperm analysis disruption. Furthermore, a notable restoration of the tissue content of antioxidants (catalase and reduced glutathione) but depletion of malondialdehyde was evident in MO-ZNPs+ACR-treated rats compared to ACR-exposed ones. In addition, MO-ZNPs oral dosing markedly rescued the histopathological changes and apoptotic caspase-3 reactions in the testis resulting from ACR exposure. Furthermore, in MO-ZNPs+ACR-treated rats, ACR-induced downregulation of testicular steroidogenesis genes and proliferating cell nuclear antigen (PCNA) immune-expression were reversed. Conclusively, MO-ZNPs protected male rats from ACR-induced reproductive toxicity by suppressing oxidative injury and apoptosis while boosting steroidogenesis and sex hormones.

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.

Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats

ObjectiveThis study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats. MethodsThirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed. ResultsBBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250–500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05). ConclusionBBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.The graphical abstract is available on the website www.besjournal.com.

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.

Effectiveness of Withania frutescens root extract on testicular damage induced by lead acetate in adult albino rats

Withania frutescens was used previously in traditherapy against poisoning, gastric ulceration, and dysentery treatments. Because no previous studies reporting on its therapeutic effects on male reproductive system and fertility disorders, this study aims to examine its effect on lead induced testicular damages as well as sperm count and hormonal status in rats. The present study is performed to determine their phytochemical compositions using GC-MS analysis, their antioxidant and anti-inflammatory activities in-vitro using spectrophotometry and then to estimate testosterone levels, sperm count, histopathological features, as well as spermatogenesis (TDI) and spermiogenesis (SPI) indices. The experiment is conducted for three months using four groups (Group A: control rats; Group B: exposed rats to lead-acetate; Group C: exposed rats to lead-acetate and 200 mg/kg of W. frutescens extract; Group D: treated rats with 200 mg/kg of W. frutescens extract). The obtained results show a total of 10 identified components from GC-MS analysis. Whereas a total phenolic content of 63.23 ± 3.82 GAE/g of extract, 25.16 ± 1.21 µg/mL of anti-free radical activity, and reducing power of 163.19 ± 6.01 µg/mL. A high anti-inflammatory activity is determined by hemolysis inhibition (IC50 =12.71 ± 1.06 µg/mL) and protein denaturation inhibition (IC50 =6.8 ± 1.23 µg/mL). Besides, lead exposure causes histological alterations in testis and decreases serum testosterone level, sperm count, and TDI and SPI indices. W. frutescens treated and co-treated animals showed no toxic effects throughout the experiment. However, it is found to improve testosterone level, increase sperm count, attenuate the testicular histopathological effect of lead, and increase TDI and SPI. These findings . these findings suggest that W. frutescens is a better source of bioactive compounds, which play an effective role against lead testicular damages. Furthermore, this natural extract can be utilized potentially in pharmaceutical and medicinal applications.

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.

Molecular Hydrogen Reduces Electromagnetic Pulse-Induced Male Rat Reproductive System Damage in a Rodent Model.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.

Effects of diet-induced obesity and its correction on sex hormone levels and behavioral featurеs of male Wistar rats

Obesity causes a wide range of pathophysiological consequences in the body, affecting the sphere of hormonal and psycho-emotional regulation. The aim of the study is to investigate the effect of a high-calorie diet on the development of obesity, reproductive status hormone levels and behavioral features of male Wistar rats, as well as the possibility of normalizing the identified shifts with non-medicinal options for obesity correction. Experiments were performed on 80 sexually mature male Wistar rats for 16 weeks and included 6 groups of animals, taking into account the diet (standard vivarium diet, highcalorie diet and transition from a high-calorie diet to a standard diet at the 2nd stage of the experiment) with or without the moderate physical activity in the form of treadmill running at the 2nd stage – the last 8 weeks of the experiment. A longterm high-caloric diet (16 weeks) caused visceral obesity, elevated glucose, cholesterol and triglyceride levels, dramatically decreased serum testosterone and estradiol levels, and depression manifestations in the Porsolt test in male Wistar rats. Successful correction of obesity, metabolic shifts and depressive behavior in rats was achieved by switching to a balanced diet during the last 8 weeks of the experiment. Normalization of testosterone and estradiol levels against the background of an increased serum luteinizing hormone level occurred in rats receiving a high-calorie diet (16 weeks) with the connection of physical exercise during the last 8 weeks of the experiment. Complex correction of obesity, which included the transition to a standard diet and exercise during the last 8 weeks of the experiment, led to a dramatic 2-fold increase in testosterone levels compared to control and a hyperactive phenotype in male Wistar rats. There is a close relationship between the depression development and testosterone levels in obesity and its correction.

Increased risk of primary ovarian insufficiency by high-fructose diet consumption: a 90-day study in female rats.

There is ambiguous evidence that high-fructose diet can induce toxicity in different organ systems but its endocrine disrupting effects by abnormal changes in female reproductive organs is poorly evidenced. This study aimed to address the reproductive safety of high fructose diet through clinical, biochemical, hormonal, histopathological, and immunohistochemical analysis. For this purpose, 5-6weeks mature female Wistar rats were divided in three groups and each five animals/group exposed to standard chow + water + HFCS-55, standard chow + water + sucrose 75%w/v and standard chow + water for 90days. Remarkable increase in most lipid profile factors and total body weights of HFCS-55 fed rats and sucrose fed rats were detected in similar pattern compared to control. At the same time, a battery of differential signs and symptoms in HFCS-fed groups including squamous metaplasia in the uterine tissue and ovarian congestion, significant increase in FSH and LH levels, meaningful decreased serum testosterone and 17β-estradiol levels, and strong androgen receptor expression in ovaries and uterine of HFCS group of animals were recorded compared to other two study groups. These thought-provoking signs and signals of fructose induced reproductive toxicity in this model emphasis the contribution of HFCS-55 to deteriorated ovarian and endometrial health and increased risk primary ovarian insufficiency (POI) in women.

Exposure of carbon nanotubes affects testis and brain of common carp

Carbon nanotubes production has been rapidly increasing for many potential applications, however, the environmental impact of this nanomaterial needs to be comprehended. The present work focused on unraveling the effects of single-walled carbon nanotubes (SWCNT) in the common carp, Cyprinus carpio. The physicochemical properties of SWCNT were analyzed with X-ray diffraction, Fourier transforms infra-red, UV-Vis absorption, transmission electron microscopy (TEM), and Raman spectroscopy before testing for exposure impact. The effects of SWCNT, were investigated by exposing to two doses viz., 10 and 50 μg/L, for 7 days in adult common carp, in vivo. Expression of key steroidogenic and transcription factor genes related to testis and brain were downregulated after the treatment. The concomitant decreases in serum testosterone and 11-ketotestosterone levels revealed the impact of SWCNT after exposure. Further, SWCNT exposure induced antioxidant enzymes namely glutathione-S-transferases, superoxide dismutase, and catalase in both testis and brain. Concurrently, histological and TEM analysis of testis revealed structural disarray. In addition, SWCNT treatment, in testicular and brain primary cell cultures decreased cell viability with an increase of reactive oxygen species levels, leading to a significant elevation of apoptotic cells. In line with this, low mitochondrial membrane potential and DNA damage were also observed during post SWCNT treatment. Taken together, transient exposure of SWCNT causes toxic effects and alters testicular and brain function in the common carp. Thus, the discharge of carbon nanotubes poses a greater risk to the aquatic environment warranting regulatory measures.

Obstructive sleep apnea and serum total testosterone: a system review and meta-analysis.

Testosterone deficiency (TD) negatively affects male sexuality, reproduction, general health, and quality of life. In recent years, decreased serum testosterone levels have been reported to be caused by obstructive sleep apnea (OSA). However, these results are controversial and lack the support of a large number of high-quality studies. Hence, we performed a meta-analysis to assess the association between OSA and serum testosterone levels. To identify eligible studies, we conducted a systematic retrieval in the electronic databases (PubMed, Web of Science, the Cochrane Library, EMBASE) from their inception to September 2021. We chose studies with definitive diagnoses of OSA, including effects of OSA on testosterone level. Random effect model was used for analysis. This meta-analysis included 24 case-control studies with 1389 patients (1268 male patients) and 845 controls (745 male control). The serum testosterone levels in the male OSA group were significantly lower than that of control group [SMD = - 0.97, 95% CI (- 1.47, - 0.47)], while there was no difference in female patients withOSA and control [SMD = 0.06, 95% CI (- 0.22, 0.33)]. Subgroup analysis showed that race, age, body mass index (BMI), and detection method were the reason for high heterogeneity (I2 = 94.9%). The results indicated that OSA is significantly correlated with the decrease in serum testosterone levels in men. Male patients with OSA should be alerted to secondary diseases caused by low testosterone levels.

Cadmium exposure induces pyroptosis in testicular tissue by increasing oxidative stress and activating the AIM2 inflammasome pathway

High doses of cadmium (Cd) cause irreversible injury to the reproductive system, especially testicular tissue. Studies have shown that pyroptosis is involved in Cd-induced tissue damage, but whether pyroptosis is involved in damage to testicular tissue following Cd exposure remains unclear. To investigate the mechanism of pyroptosis in testicular injury induced by Cd exposure, we used 8-week-old male C57BL/6J mice subjected to consecutive 7 days of intraperitoneal injection of cadmium chloride (CdCl2) at concentrations of 0, 1.0 and 3.0 mg/kg. The results indicated that 3.0 mg/kg CdCl2 significantly decreased serum testosterone levels, sperm concentration and sperm motility, while increased LDH and IL-1β levels. Testicular HE staining indicated that Cd exposure damaged the interstitial cells and increased the atypical residual bodies. Fluorescence results indicated that 3.0 mg/kg CdCl2 increased ROS levels, DNA damage, and the number of TUNEL-positive seminiferous tubule cells in testicular tissue. Transcriptome analysis showed that Cd exposure mainly induced inflammatory and chemokine signaling pathways in testicular tissue, with upregulated mRNA levels of Aim2, and reduced mRNA levels of Nlrp3. Further analysis showed that 3.0 mg/kg CdCl2 increased the expression of testicular HO-1, SOD2, γH2AX and PARP-1, as well as the pyroptosis-related factors GSDMD, GSDME, Caspase-1, ASC and IL-1β. In conclusion, our results provide a possible mechanism by which Cd exposure activates the AIM2 pathway by increasing oxidative stress injury to induce pyroptosis in testicular tissue. This provides a new perspective on testicular damage caused by Cd exposure.

Allium Cepa (Onion) Extract Enhances and Protects Testicular Function and Architecture against Paraquat Induced Oxidative Damage.

Allium cepa (A. cepa) is consumed for its health benefits. This study investigated the therapeutic potentials of ethanolic extract of A. cepa bulbs against paraquat-induced testicular toxicity in animal model. Thirty Wistar rats were split into control and five test groups (n=5). Group A (Control) received feed and water; test groups (B-F) were treated orally as follows: group B (20 mg/kg b.w. of paraquat for 4weeks); group C (1000 mg/kg b.w. of A. cepa extract for 4weeks); group D (a co-administration of 20 mg/kg b.w. of paraquat and 100 mg/kg b.w. of A. cepa extract for 4weeks); group E (a co-administration of 20 mg/kg b.w. of paraquat and 1000 mg/kg b.w. of A. cepa extract for 4weeks); and group F (1000 mg/kg b.w. of A. cepa extract for 2weeks before co-administration with 20 mg/kg b.w. of paraquat for 2weeks). In the end, sperm count, morphology, motility, sera testosterone levels, malondialdehyde (MDA) and superoxide dismutase (SOD) levels as well as histology of the testes were assessed. Paraquat administration caused significantly (P&lt;0.05) reduced sperm count, motility, alteration in sperm morphology and induced cell death. Oral gavage of paraquat also caused significant (P&lt;0.05) decrease in serum testosterone and SOD levels with concomitantly elevated MDA levels. However, following the co-administration with ethanolic extract of A. cepa to experimental rats, there was an improvement in sperm parameters (count, motility and morphology) as well as in sera testosterone and SOD levels. It can be concluded that A. cepa exerts strong antioxidant effects in a dose-dependent manner in ameliorating testicular toxicity induced by paraquat in animal models.

Gestational diabetes mellitus suppresses fetal testis development in mice

The prevalence of gestational diabetes mellitus (GDM) is increasing rapidly. In addition to the metabolic disease risks, GDM might increase the risks of cryptorchidism in children. However, its mechanism involved in abnormalities of the male reproductive system is still unclear. The purpose of this study was to study the effects of GDM on the development of mouse fetal Leydig cells (FLCs) and Sertoli cells (SCs). Pregnant mice were treated on gestational days 6.5 and 12.5 with streptozotocin (100mg/kg) or vehicle (sodium citrate buffer). Leydig cell and SC development and functions were evaluated by investigating serum testosterone levels, cell number and distribution, genes, and protein expression. GDM decreased serum testosterone levels, the anogenital distance, and the level of desert hedgehog in SCs of testes of male offspring. FLC number was also decreased in testes of GDM offspring by delaying the commitment of stem Leydig cells into the Leydig cell lineage. RNA-seq showed that FOXL2, RSPO1/β-catenin signaling was activated and Gsk3β signaling was inhibited in GDM offspring testis. In conclusion, GDM disrupted reproductive tract and testis development in mouse male offspring via altering genes related to development.