Testicular Function Research Articles

An Overview of the Mechanisms of Cadmium-induced Toxicity in the Male Reproductive System

Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.

SAT282 Hypogonadism In Men With Congenital Adrenal Hyperplasia. A Retrospective Longitudinal Analysis With A Special Focus On Testicular Adrenal Rest Tumors And 11-oxygenated Androgens

Abstract Disclosure: M.K. Auer: None. C. Lottspeich: None. M. Bidlingmaier: None. H.F. Nowotny: None. L. Tschaidse: None. R.J. Auchus: None. N. Reisch: None. Background: Hypogonadism is a common issue in men with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). While this is mostly resulting from extra-gonadal steroid production, testicular function may also be impaired due to the presence of testicular adrenal rest tumors (TART). In addition to their local compressive effects, it has recently been demonstrated that TART are a source of 11-oxygenated androgens that might impair testicular function. Little is known about the long-term course of testicular function in men with 21OHD in general and the role of potential influential factors such as presence of TART and 11-oxygenated androgen formation in particular. Methods: Retrospective single-center study in 30 men with classic 21OHD (N = 11 with TART, N = 16 without TART, N = 3 unknown TART status). Median age at baseline was 31.0 years (IQR 26-38). Median observation period was 12 years (IQR 8-13). The median number of outpatient visits and blood samplings per patient during this time was 8.5 (IQR 6-10). Testosterone (T), 17-hydroxyprogesterone (17-OHP), androstenedione (A4) and 11-oxygenated androgens were measured simultaneously from stored serum samples by LC-MS/MS. Results: On average, 43.2% (No TART) and 54.6% (TART) of all T measurements in each patient were below the reference range (n.s.). In most patients, gonadotropin levels were normal or suppressed. In univariate as well as multivariate mixed model analysis, including age, BMI, type of glucocorticoid (GC), GC-equivalence dosage and phenotype (salt wasting vs simply virilizing), T levels were comparable between men with and without TART. While T levels remained stable during the observation period in men without TART (Baseline 11.37 ± 1.52 nmol/l, last visit 12.1 ± 2.1 nmol/l) they increased in those with TART (Baseline 9.48 ± 1.68 vs. last visit 14.9 ± 2.3 nmol/l (Time*Group F1,7.247 = 7.558; p = 0.006). At baseline, the A4/T-ratio as a marker of adrenal T production was significantly higher in men with TART (1.39 ± 1.63) than in those without (0.27 ± 1.63), and there was a Time*Group interaction, again indicating a decrease in the A4/T-ratio in men with TART (F1,47.843 = 2.008; p = 0.04). This resulted in only a trend for the A/T-ratio being higher in men with TART (0.5 ± 1.6 vs 0.3 ± 1.5; p = 0.057) across the whole observation period. 11-ketotestosterone levels were higher in men with TART (1.8 ± 0.006 pg/ml) than in men without TART (0.68 ± 0.006 nmol/l) but remained unchanged over time in both groups. Conclusion: A normal serum T does not exclude hypogonadotropic hypogonadism in men with 21OHD, which is a common problem that appears to remain stable in the long run. The presence of TART does not have a negative effect on T-levels. In contrast, the detection of TART should prompt further assessment, including A4, gonadotropins, and 11-ketotestosterone, followed by treatment optimization to improve gonadal T production. Presentation: Saturday, June 17, 2023

SAT286 Effect of Tildacerfont On Gonadotropins And Testicular Steroidogenesis In Men With Classic 21-hydroxylase Deficiency

Abstract Disclosure: R. Charlton: Employee; Self; Spruce Biosciences, Inc. A. Khattab: Consulting Fee; Self; Antares Pharma, Inc. R.J. Auchus: Grant Recipient; Self; Spruce Biosciences, Inc. Research Investigator; Self; Spruce Biosciences, Inc. Impaired testicular function is a common comorbidity of classic 21-hydroxylase deficiency (21OHD). Testicular adrenal rest tumors (TART) can disrupt testicular architecture and cause primary hypogonadism. Both supraphysiologic glucocorticoid doses and adrenal-derived androgens and estrogens can suppress gonadotropins and cause secondary hypogonadism. We conducted a post-hoc analysis of gonadal axis function in men with 21OHD participating in SPR001-201 and SPR001-202, two phase 2 studies of tildacerfont, a once-daily oral corticotrophin-releasing factor receptor 1 (CRFR1) antagonist, designed to reduce ACTH and adrenal steroid production, including androstenedione (A4). Study 201 included 3 cohorts: Cohort A, 5 men who received tildacerfont in a 6-week dose escalation - 2 weeks at 200 mg QD, 2 weeks at 600 mg QD, and 2 weeks at 1000 mg QD without washout between doses; Cohort B, 1 man who received tildacerfont for 2 weeks at 200 mg BID; and Cohort C, 4 men who received tildacerfont for 2 weeks at 100 mg BID. Study 202 included 4 men who received tildacerfont 400 mg QD for 12 weeks. Participants continued their previously prescribed glucocorticoid ± mineralocorticoid replacement without dose adjustments. Geometric means were used to describe hormone levels due to the small participant numbers. Mean and median ages were 46/32y in Study 201 and 32/35y in Study 202 (range 18-54 in both studies). All participants reported race as white except one who identified as white and Asian. Four reported ethnicity as Hispanic or Latino. At baseline, testosterone (T) levels were normal except for four 201 participants that had T <300 ng/dL. At baseline, 6/11 (55%) had suppressed LH (including the four with low T), and 11/14 (79%) had A4/T ratios >1, indicating a predominantly adrenal origin of T. In Study 201, mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, mean T levels were 448.4 ng/dL at baseline and 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4) (normal 1.8-8.6IU/L). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Of the four men who had low T and suppressed LH (hypogonadotropic hypogonadism), LH rose in all 4 and normalized in 3/4 (75%). Mean A4/T ratios decreased across both studies. In Study 201, the mean declined from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T ratio decreased from baseline of 2.44 to 0.68 at week 12. All the hypogonadal men experienced reductions in A4/T ratios, and 3/4 (75%) achieved A4/T <1. This post-hoc analysis highlights that gonadal axis disruption is common in men with 21OHD and suggests that modulation of adrenal androgen production via CRFR1 antagonism may improve testicular function. Presentation: Saturday, June 17, 2023

THU098 Gonadotropin Secreting Pituitary Tumor Presenting As Primary Hypogonadism

Abstract Disclosure: J.N. Shapiro: None. T.X. Lu: None. J. Eapen: None. J.G. Karam: None. Gonadotroph adenomas are the most common subtype of nonfunctional pituitary adenomas, with 35 percent secreting enough LH or FSH to raise serum gonadotropin levels, but clinical syndromes due to hypersecretion of gonadotropins are rare. A low testosterone level with high FSH or LH can mislead to a diagnosis of concomitant primary hypogonadism rather than a secreting pituitary adenoma. We present a case of a patient with an FSH-secreting pituitary macroadenoma presenting with low testosterone levels. The patient is a 67-year-old man incidentally found to have a pituitary macroadenoma measuring 12 x 13 x 12 millimeters, impinging upon the optic chiasm on MRI of the brain obtained for headaches. Visual field tests revealed abnormalities compatible with glaucoma, but not chiasm compression. He has no symptoms of hormonal excess or deficit, although his wife reported decreased erectile function. Physical examination was unremarkable except for an atrophic left testicle. Pituitary hormone function tests (ACTH, AM cortisol, IGF-1, prolactin, thyroid function tests, and 24-hour urine free cortisol) were within normal range, except for an elevated FSH 14.8-18.1 mIU/mL and decreased testosterone in range of 185-256 ng/dL, with normal LH at 7.0 mIU/mL, for which he was referred for urology for evaluation of primary hypogonadism. The patient underwent transsphenoidal resection of the pituitary adenoma. Postoperative pathology revealed a pituitary adenoma, gonadotroph cell type, with immunohistochemical staining scattered positive FSH, and rare positive LH. Postoperative MRI showed post-surgical changes with no residual nodular enhancement. Following surgery, the patient suffered from severe clinical hypogonadism with episodes of profuse diaphoresis and extreme fatigue. Postoperative laboratory values revealed panhypopituitarism with undetectable testosterone level, and low LH and FSH levels. The patient was successfully treated with hydrocortisone, levothyroxine, and testosterone, with resolution of his symptoms. Our patient presented with a pituitary macroadenoma, low testosterone, and high FSH suggestive initially of primary hypogonadism, but found ultimately to have an FSH-secreting adenoma. He likely had underlying hypogonadism, primary or secondary, and although his adenoma secreted FSH, it was not enough to maintain testosterone level in normal range, possibly in part due to biologically inactive FSH molecules or to primary testicular failure. The extremely low testosterone levels postoperatively suggest that his testicular function was mostly stimulated by the adenoma secreted FSH and was therefore drastically lost after surgery. This case increases awareness to consider a gonadotropin-secreting tumor in the differential diagnosis of a pituitary adenoma with high FSH or LH, even when testosterone level is unexpectedly low. Presentation: Thursday, June 15, 2023

OR25-02 Hunting The Magic Bullet In Treating Male Secondary Hypogonadism Associated With Metabolic Syndrome: Results Of a Prospective Study Comparing Liraglutide Vs. Gonadotropins

Abstract Disclosure: S. La Vignera: None. R.A. Condorelli: None. A.E. Calogero: None. R. Cannarella: None. E. Greco: None. A. Aversa: None. Background: Previously, we hypothesized a role for glucagon-like peptide-1 (GLP1) analogs in the treatment of male infertility (DOI: 10.1111/andr.13015), although no studies have so far investigated this issue. Purpose: To prospectively investigate the effects of treatment with liraglutide, a GLP1 analog, on reproductive and sexual function in men with functional hypogonadism of childbearing age. Patients and Methods: 110 obese men of childbearing age (18-35 years) with functional hypogonadism were enrolled and divided into three groups based on their desire to have children. Group A consisted of men actively seeking paternity, Group B of men who did not seek paternity, and Group C of men who had already fathered a child. Group A was treated with gonadotropins [urofollitropin 150 IU three times a week and human chorionic gonadotropin (hCG) 2000 IU twice a week], Group B with liraglutide (3 mg daily), and Group C with transdermal testosterone (60 mg daily). The following endpoints were measured at enrolment and after 4 months: anthropometric and metabolic parameters, gonadotropins, total testosterone, conventional sperm parameters (Group A and B only), the score of the International Index of Erectile Function 5 Items (IIEF5), and frequency of phosphodiesterase type 5 inhibitors (PDE5i) use. Results: The groups did not differ on any of the baseline endpoints. Weight, body mass index, and waist circumference significantly decreased after treatment in Group B, but not in the other Groups. Liraglutide significantly increased LH (3.2±0.2 IU/L vs. 2.0±0.3 IU/L; p<0.01), FSH (2.6±0.2 IU/L vs. 1.6±0.3 IU/L; p<0.01), total testosterone (4.1±0.5 ng/mL vs. 1.4±0.6 ng/mL; p<0.05), and sex hormone-binding globulin (36.0±4.0 nmol/L vs. 14.0±3.0 nmol/L) levels from baseline, while no improvement was observed in the other Groups. Liraglutide increased sperm concentration (16±4 mil/ml vs. 6±2 mil/ml; p<0.05), progressive motility (34±4 % vs. 14±2 %; p<0.01), and morphology (10±2 % vs. 4±2 %; p<0.05), while treatment with gonadotropins only increased sperm progressive motility (19±2 % vs. 12±3 %; p<0.05) compared to baseline. The IIEF-5 score improved after liraglutide treatment (4±2 vs. 21±4; p<0.05), while no significant changes were observed in the other Groups. Similarly, PDE5i use decreased significantly in Group B (31%), compared with Groups A (48%) and C (45%). Conclusions: Liraglutide is an effective weight loss drug, which also improves serum gonadotropin and total testosterone levels, sperm conventional parameters, and sexual function in obese patients with functional hypogonadism seeking parenthood. This is the first study documenting the efficacy of liraglutide on the testicular function of these patients. Presentation Date: Saturday, June 17, 2023

Would It be Possible for a SARS-CoV-2 Infection to Affect the Male Reproductive System?

The male reproductive system may be affected by the systemic infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The precise mechanisms of male reproductive impairment are not well known. There are two possible mechanisms for the effect of SARS-CoV-2 on the male reproductive system either directly through the impact of the angiotensin-converting enzyme 2 (ACE2) receptor on testicular tissue or indirectly through the effect of the secondary autoimmune response on testicular functions. The second mechanism is more likely. Extensive studies need to be conducted on the impact of SARS-CoV-2 on the functional characteristics of sperm and the results of natural fertilization or assisted reproductive technology.

Exposure to bromoxynil octanoate herbicide induces oxidative stress, inflammation, and apoptosis in testicular tissue via modulating NF-кB pathway.

Bromoxynil octanoate (BO) is a herbicide necessary for plant growth and production. However, it may cause damage to environment and humans. This study aimed to investigate the potential testicular toxicity of BO and its possible underlying mechanisms. Male Albino (Sprague Dawley) rats were administered BO in different doses (5, 10, 20, and 40mg/kg/BW; P.O.) daily for 21 days. Testicular function was evaluated by determining count and viability of epididymal sperm, and testosterone. In addition, the following parameters were assessed; MDA, NO, and H2O2 as oxidative stress markers; SOD, CAT, GPx, GST, and GSH as antioxidant markers; NF-ĸB-P65 and IL-18 as inflammatory markers; caspase-9 and caspase-3 as apoptotic markers; gene expression of NF-ĸB-P65, TNF-α, BAX, Bcl-2, and caspase-3; and histopathological examination of epididymis and testis sections. The results showed a significant (P<0.05) increase in MDA, NO, H2O2, IL-18, and caspase-9 content, NF-ĸB-P65, TNF-α, Bax, and Caspase-3 expression as compared to control. Furthermore, the count and viability of epididymal sperm, testosterone level, SOD, CAT, GPx, GST, and GSH content, and Bcl-2 expression showed a significant (P<0.05) decrease as compared to control. In conclusion BO-induced testicular damage by altering oxidation, inflammation, and apoptosis.

Physiological responses of rabbit buck fed diets supplemented with varied levels of nutmeg seed meal, clove leaf meal, and their composite mix

Abstract Fifty-six Hyla breeds of 12-week-old rabbit bucks were randomly distributed across 7 diet groups comprising the control, 0.25% nutmeg seed meal (NSM), 0.50%, 0.25% clove leaf meal (CLM), 0.50% CLM, 0.25% composite nutmeg and clove leaf meal mix (CNCM), and 0.50%CNCM. At the end of the 8 weeks of the experiment, 3 bucks per diet group were sacrificed. The growth performance, haematology, serum biochemical indices, and testicular morphometry of the buck were assessed. The different diet groups significantly increased (P&lt;0.05) the feed intake, weight gained, and feed conversion ratio compared to the control. The highest weight gained and best feed conversion ratio were observed among bucks fed 0.25% CNCM. Dietary supplementation of NSM, CLM, and CLCM at 0.25 and 0.50% levels did not affect (P&gt;0.05) the blood parameters, serum proteins, enzymes, and metabolites except for serum glutathione and catalase activity which revealed that the phytochemicals in NSM and CNCM could effectively combat free scavenging radicals. Testicular weight and densities were positively influenced (P&lt;0.05) by dietary supplements which are indicative of better testicular functions compared to the control. Hence, the synergetic effect of NSM and CLM at 0.25% supplementation level could be incorporated into Bucks’ diet for better productivity.

Pathological, biochemical and hormonal changes associated with prolonged administration of methanol extract of &lt;i&gt;Garcinia kola&lt;/i&gt; seed in adult male Wistar rats.

Garcinia kola (GK) seed is believed to possess aphrodisiac properties hence its traditional use to manage erectile dysfunctions in man. However, there has been conflicting reports of its long-term effects on the male reproductive organs. In this study, the effect of varying doses of methanol extract of GK on testicular function and structure in Wistar rats was evaluated. Forty adult male rats (350-360g) were randomly divided into 4 groups. Groups 1, 2 and 3 received oral doses of 600mg/kg, 400mg/kg and 100mg/kg of the extract daily, respectively for 70 days while group 4 (control group) received normal saline (0.9% NaCl). Blood samples were collected fortnightly from each rat for serum chemistry and testosterone analysis. At termination, the testes, epididymides and livers were harvested, weighed and fixed in 10% neutral buffered formalin and processed for histopathology. The results were presented as mean ± standard error of mean (SEM) and analyzed using one way analysis of variance (ANOVA) at P&lt; 0.05. Dose-related pathological changes were observed in the testes and epididymides. Testicular weight decreased significantly (p&lt;0.05) in 400mg/kg and 600mg/kg groups compared to the control group. There was testicular necrosis associated with distortion of the seminiferous tubular wall and reduced seminiferous tubular diameter. Seminiferous tubules had reduced germinal epithelial thickness along with an absence of viable spermatids and spermatozoa. Serum testosterone levels decreased progressively (p &lt; 0.01) in groups 1 and 2 while those of groups 3 and 4 remain unchanged. The results established that ingestion of methanol extracts of GK seed at the dose of 400mg/kg and 600mg/kg produced significant gonadal pathology in adult male Wistar rats despite the absence of remarkable hepatic biochemical and structural changes.

Impact of Cushing's syndrome on the gonadotrope axis and testicular functions in men.

Does Cushing's syndrome (CS) differently affect the gonadotrope axis and testicular functions (GA/TF) according to the hypercortisolism intensity and underlying etiology? Endogenous cortisol excess caused by CS leads to varying degrees of hypogonadotropic hypogonadism (HH) with more severe GA/TF impairment and altered spermatogenesis in men with intense hypercortisolism associated with paraneoplastic/ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS). CS is very rarely studied in men due to its lower prevalence in men than in women. In a few old reports focusing exclusively on a limited number of men with Cushing's disease (CD), the occurrence of hypogonadism was reported. However, a detailed assessment of the impact of CS on the GA/TF in a significant series of patients has not been performed. Yet, hypogonadism could worsen CS-associated comorbidities such as osteoporosis and myopathy. To date, the full spectrum of GA/TF impairment in men with CS of different etiologies and intensity remains unknown. In this monocentric study, 89 men with CS diagnosed at a tertiary endocrine university center (Bicêtre, Paris Saclay) between January 1990 and July 2021 were evaluated and compared to 40 normal men of similar age. The CS patient cohort of 89 men included 51 with CD, 29 with EAS and 9 with CS of adrenal origin i.e. (ACTH-independent CS (AI-CS)). They all had frank hypercortisolism, with increased 24 h-urinary-free cortisol (24 h-UFC) in two separate samples. A case-control study was performed focusing on pituitary gonadotrope function and testicular sex steroids and peptides. An additional set of six CS men had an evaluation including semen analysis. In a subgroup of 20 men with available data after CS remission, a longitudinal analysis was conducted to assess the reversibility of GA/TF defects. Compared to controls, men with CS had significantly lower total testosterone (TT), bioavailable TT, and free TT (P < 0.0001). Hypogonadism, defined as serum TT levels <3.0 ng/ml, was present in 83% of men with EAS, in 61% of men with CD, and in 33% of men with AI-CS. Low-normal LH concentrations in the included men with hypercortisolism indicated HH. Serum sex hormone-binding globulin levels were moderately decreased in men with CD (P = 0.01 vs controls). Among the CS men, those with EAS had significantly lower TT, LH, and FSH levels than those with CD or AI-CS. When compared to controls, patients with EAS were the only group exhibiting a significant decrease in both serum FSH (P = 0.002) and the testicular peptides inhibin B (P < 0.0001) and anti-Müllerian hormone (P = 0.003). Serum INSL3 levels were significantly lower in men with CD than in the controls (P = 0.03). Of note, 24 h-UFC and ACTH were inversely and significantly associated with the majority of reproductive hormones including LH, FSH, TT, and inhibin B. Following successful curative therapy, reproductive assessment at a mean of 6.0 ± 4.3 years showed a significant increase in serum TT (P < 0.0001) and plasma LH (P = 0.02) levels, indicating a reversal of HH in 75% of the affected males. Among the six patients with available semen analysis, the two EAS cases exhibited a decrease in Sertoli cell peptides associated with a severe oligozoospermia, which completely normalized following removal of the source of hypercortisolism. The potential bias due to the retrospective design is counteracted by the analysis of the largest male CS cohort to date as well as the use of stringent inclusion and exclusion criteria. Due to the low number of patients with semen analysis in this study, further research is needed to unravel the full spectrum of spermatogenesis defects in men with CS. This work reveals the variable spectrum of reproductive impact in men with CS. We demonstrate that GA/TF impairment depends on the intensity of hypercortisolism which in turn is related to the underlying etiology. The causal link between hypercortisolism and GA/TF impairment was attested by its reversibility in most patients after CS remission. The wider implications of our findings lie in the potential generalization to a much commoner entity, iatrogenic CS due to chronic exposure to exogenous glucocorticoids. Several research grants were attributed to J.Y.: (i) a grant from Programme Hospitalier de Recherche Clinique (PHRC # P081212 HYPOPROTEO); (ii) a grant from the French Association of Patients with Adrenal Diseases ('Association surrénales'); and (iii) independent Investigator Research Grants from HRA Pharma, Novartis and Recordati Pharma. A SICPA Foundation grant (Lausanne, Switzerland) allowed protected research time for G.E.P. The above sponsors were not involved in any part of the study. The authors have no competing or other conflicts of interest to declare. N/A.

Ameliorative effect of hesperidin against high dose sildenafil-induced liver and testicular oxidative stress and altered gene expression in male rats

BackgroundThe clinical use of sildenafil citrate (Viagra), a drug used to treat erectile dysfunction, is limited because of its many side effects on tissues. In this context, we aimed to investigate the protective effects of hesperidin, a citrus flavonoid, on hepatic and testicular damage induced by a high dose of sildenafil citrate in male rats. Rats were randomly divided into four groups. The first group was used as the control group. The second group was orally administered sildenafil citrate at a high dose of 75 mg/kg thrice a week. In the third group, hesperidin was administered orally at a dose of 50 mg/kg/day. The fourth group was administered 75 mg/kg sildenafil citrate three times a week with 50 mg/kg hesperidin daily. The experiment lasted for 28 days.ResultsIn the sildenafil-treated groups, blood indices were altered, liver function tests were deranged, and serum testosterone levels were reduced. In the liver and testicular tissue, sildenafil citrate treatment resulted in significant reductions in catalase and total antioxidant capacity; as well as increased malondialdehyde, reactive oxygen species, and nitrous oxide levels. In addition, sildenafil citrate treatment caused abnormal histopathological patterns in both the liver and the testes. Liver vascular endothelial growth factor and testicular steroidogenic acute regulatory protein gene expression were upregulated.ConclusionsHesperidin attenuated the harmful effects of intensive sildenafil citrate treatment on liver and testicular functions, alleviated oxidative stress and normalized blood indices. Therefore, hesperidin could be protective against sildenafil citrate-induced oxidative damage that may develop over the long term.

Omega-3 fatty acid ameliorates bisphenol F-induced testicular toxicity by modulating Nrf2/NFkB pathway and apoptotic signaling.

Bisphenol F (BPF) has been shown to disrupt testicular functions via perturbation of testicular redox balance, while omega-3 fatty acid (O3FA) has been established to exert antioxidant and anti-inflammatory activities. Therefore, this study focused on the role and associated molecular mechanism of O3FA in BPF-induced testicular dysfunction in male Wistar rats. Twenty-four (24) rats were randomly grouped after two weeks of acclimatization into four (4) groups (n=6/group); the vehicle-treated control group, BPF treated group received 30 mg/kg of BPF, and the intervention groups received 30 mg/kg BPF + 100 mg/kg O3FA (BPF+O3FA-L) and 30 mg/kg BPF + 300 mg/kg of O3FA (BPF+O3FA-H). All treatment lasted for 28 days. Low and high doses of O3FA ameliorated BPF-impaired sperm quality, and induced hormonal imbalance, accompanied by a distortion in testicular histology and elevated testicular injury markers. Furthermore, co-administration of BPF with both doses of O3FA blunted BPF-induced redox imbalance, inflammatory response, and apoptosis. In conclusion, our present findings show that O3FA improves testicular functions in BPF-treated rats by improving sperm quality and reproductive hormones via the maintenance of testicular redox balance.

Impacts of elevated temperature on morphology, oxidative stress levels, and testosterone synthesis in ex vivo cultured porcine testicular tissue

Heat stress has been recognized as a major environmental factor affecting reproductive performance in livestock. However, the underlying mechanisms through which high temperature impairs testicular function remain elusive. This study aimed to investigate the effects of high temperature on morphology, oxidative stress levels, and testosterone synthesis in porcine testicular tissue in vitro. Testicular tissue samples from boars were subjected to different temperature conditions: control (37 °C) and heat stress (39 °C) for 4 h. The morphology of the testicular tissue was assessed using histological analysis, while oxidative stress levels were evaluated by measuring reactive oxygen species (ROS) production and antioxidant enzyme activities. Additionally, the expression of key enzymes involved in testosterone synthesis was examined using quantitative real-time polymerase chain reaction (qRT-PCR). Our results revealed that exposure to high temperatures significantly altered testicular tissue morphology. Histological analysis demonstrated degeneration and disorganization of seminiferous tubules, reduction in germ cell populations, and disruption of the blood-testis barrier. Moreover, high-temperature exposure significantly increased ROS production and decreased the activities of antioxidant enzymes (p < 0.05), indicating elevated oxidative stress levels in the testicular tissue. Furthermore, qRT-PCR analysis showed that high-temperature exposure suppressed the expression of key enzymes involved in testosterone synthesis, including steroidogenic acute regulatory protein and cytochrome P450 family 11 subfamilies A member 1. These findings suggest high temperature impairs testicular function by disrupting testicular morphology, inducing oxidative stress, and inhibiting testosterone synthesis. In conclusion, our study demonstrates that high-temperature exposure adversely affects morphology, oxidative stress levels, and testosterone synthesis in porcine testicular tissue. These findings provide insights into the potential mechanisms underlying heat-induced reproductive dysfunction in male pigs and highlight the importance of heat stress management in swine production to maintain optimal reproductive performance. Further investigations are warranted to elucidate the precise molecular pathways involved in the heat-induced testicular impairments observed in this study.

Magnetic resonance imaging based deep-learning model: a rapid, high-performance, automated tool for testicular volume measurements.

Testicular volume (TV) is an essential parameter for monitoring testicular functions and pathologies. Nevertheless, current measurement tools, including orchidometers and ultrasonography, encounter challenges in obtaining accurate and personalized TV measurements. Based on magnetic resonance imaging (MRI), this study aimed to establish a deep learning model and evaluate its efficacy in segmenting the testes and measuring TV. The study cohort consisted of retrospectively collected patient data (N = 200) and a prospectively collected dataset comprising 10 healthy volunteers. The retrospective dataset was divided into training and independent validation sets, with an 8:2 random distribution. Each of the 10 healthy volunteers underwent 5 scans (forming the testing dataset) to evaluate the measurement reproducibility. A ResUNet algorithm was applied to segment the testes. Volume of each testis was calculated by multiplying the voxel volume by the number of voxels. Manually determined masks by experts were used as ground truth to assess the performance of the deep learning model. The deep learning model achieved a mean Dice score of 0.926 ± 0.034 (0.921 ± 0.026 for the left testis and 0.926 ± 0.034 for the right testis) in the validation cohort and a mean Dice score of 0.922 ± 0.02 (0.931 ± 0.019 for the left testis and 0.932 ± 0.022 for the right testis) in the testing cohort. There was strong correlation between the manual and automated TV (R2 ranging from 0.974 to 0.987 in the validation cohort; R2 ranging from 0.936 to 0.973 in the testing cohort). The volume differences between the manual and automated measurements were 0.838 ± 0.991 (0.209 ± 0.665 for LTV and 0.630 ± 0.728 for RTV) in the validation cohort and 0.815 ± 0.824 (0.303 ± 0.664 for LTV and 0.511 ± 0.444 for RTV) in the testing cohort. Additionally, the deep-learning model exhibited excellent reproducibility (intraclass correlation >0.9) in determining TV. The MRI-based deep learning model is an accurate and reliable tool for measuring TV.

Testicular schistosomiasis: a clinico-pathological presentation of three pediatric cases and review of literature

Schistosomiasis is an important communicable disease in developing countries and an important cause of morbidity in the tropics and subtropics. It is a very rare cause of painless testicular swelling that tend to mimic malignancy and cause a diagnostic dilemma. Though histopathologic analysis confirms diagnosis, a high index of suspicion is required especially for patients presenting from endemic areas. We aim to present the clinicopathological features of three pediatric cases of Testicular Schistosomiasis (TS) and to highlight the role of high index of suspicion, incisional biopsy and histopathologic diagnosis in prevention of unwarranted orchiectomy and preservation of testicular function. We report three cases of TS in patients aged 5 years, 12 years and 14 years, who presented with progressive testicular swellings. The diagnoses were made by histopathological analysis and the patients were treated with oral praziquantel. TS should always be considered an important differential in all male children and adults presenting with testicular masses especially when they live in endemic regions. Incisional biopsy, proper histopathologic evaluation and treatment could prevent unwarranted orchiectomy and thus preserve testicular function.

The impact of vincristine on testicular development and function in childhood cancer

The impact of vincristine on testicular development and function in childhood cancer

Ameliorative Effects of Zinc Oxide, in Either Conventional or Nanoformulation, Against Bisphenol A Toxicity on Reproductive Performance, Oxidative Status, Gene Expression and Histopathology in Adult Male Rats

Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats’ reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.

Reproductive markers of testicular function and size during puberty in boys with and without a history of cryptorchidism

Reproductive markers of testicular function and size during puberty in boys with and without a history of cryptorchidism

Cloning, expression analysis and localization of DAZL gene implicated in germ cell development of male Hezuo pig

Deleted in azoospermia-like (DAZL) is essential for mammalian testicular function and spermatogenesis. To explore the molecular characterization, expression patterns, and cellular localization of the DAZL in Hezuo pig testes, testicular tissue was isolated from Hezuo pig at five development stages including 30 days old (30 d), 90 days old (90 d), 120 days old (120 d), 180 days old (180 d), and 240 days old (240 d). DAZL cDNA was first cloned using the RT-PCR method, and its molecular characterization was analyzed using relevant bioinformatics software. Subsequently, the expression patterns and cellular localization of DAZL were evaluated using quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemistry. The cloning and sequence analysis showed that the Hezuo pig DAZL cDNA fragment contained 888 bp open reading frame (ORF) capable of encoding 295 amino acid residues and exhibited high identities with some other mammals. The qRT-PCR and Western blot results indicated that DAZL was specifically expressed in Hezuo pig testes, and DAZL levels of both mRNA and protein were expressed at all five reproductive stages of Hezuo pig testes, with extremely significant higher expression levels in 90 d, 120 d, 180 d, and 240 d than those in 30 d (p < 0.01). Additionally, immunohistochemistry results revealed that DAZL protein was mainly localized in gonocytes at 30 d testes, primary spermatocytes, and spermatozoon at other developmental stages, and Leydig cells throughout five development stages. Together, these results suggested that DAZL may play an important role by regulating the proliferation or differentiation of gonocytes, development of primary spermatocytes and spermatozoon, and functional maintenance of Leydig cells in testicular development and spermatogenesis of Hezuo pig. Nevertheless, the specific regulatory mechanisms underlying these phenomena still requires further investigated and verified.

Transcriptome Studies Reveal the N6-Methyladenosine Differences in Testis of Yaks at Juvenile and Sexual Maturity Stages.

Studying the mechanism of spermatogenesis is key to exploring the reproductive characteristics of male yaks. Although N6-methyladenosine (m6A) RNA modification has been reported to regulate spermatogenesis and reproductive function in mammals, the molecular mechanism of m6A in yak testis development and spermatogenesis remains largely unknown. Therefore, we collected testicular tissue from juvenile and adult yaks and found that the m6A level significantly increased after sexual maturity in yaks. In MeRIP-seq, 1702 hypermethylated peaks and 724 hypomethylated peaks were identified. The hypermethylated differentially methylated RNAs (DMRs) (CIB2, AK1, FOXJ2, PKDREJ, SLC9A3, and TOPAZ1) mainly regulated spermatogenesis. Functional enrichment analysis showed that DMRs were significantly enriched in the adherens junction, gap junction, and Wnt, PI3K, and mTOR signaling pathways, regulating cell development, spermatogenesis, and testicular endocrine function. The functional analysis of differentially expressed genes showed that they were involved in the biological processes of mitosis, meiosis, and flagellated sperm motility during the sexual maturity of yak testis. We also screened the key regulatory factors of testis development and spermatogenesis by combined analysis, which included BRCA1, CREBBP, STAT3, and SMAD4. This study indexed the m6A characteristics of yak testicles at different developmental stages, providing basic data for further research of m6A modification regulating yak testicular development.