Testosterone Levels Research Articles

Reconstructing the Stem Leydig Cell Niche via the Testicular Extracellular Matrix for the Treatment of Testicular Leydig Cell Dysfunction

AbstractTherapies involving the use of stem Leydig cells (SLCs), as testicular mesenchymal stromal cells, have shown great promise in the treatment of Leydig cell (LC) dysfunction in aging males. However, the outcomes of these therapies are not satisfactory. In this study, it is demonstrated that the aging microenvironment of the testicular interstitium impairs the function of SLCs, leading to poor regeneration of LCs and, consequently, inefficient functional restoration. The study develops a decellularized testicular extracellular matrix (dTECM) hydrogel from young pigs and evaluates its safety and feasibility as a supportive niche for the expansion and differentiation of SLCs. dTECM hydrogel facilitates the steroidogenic differentiation of SLCs into LCs, the primary producers of testosterone. The combination of SLCs with a dTECM hydrogel leads to a significant and sustained increase in testosterone levels, which promotes the restoration of spermatogenesis and fertility in an LC‐deficient and aged mouse model. Mechanistically, collagen 1 within the dTECM is identified as a key factor contributing to these effects. Notably, symptoms associated with testosterone deficiency syndrome are significantly alleviated in aged mice. These findings may aid the design of therapeutic interventions for patients with testosterone deficiency in the clinic.

Immediate and long-term consequences of coronavirus disease 2019 on fertility and androgenic status of men

BACKGROUND: The new coronavirus disease 2019 (COVID-19) recognized as a global pandemic, impacts many human organs and systems. In view of the coronavirus widespread and high incidence of the disease in young men of reproductive potential, It would be relevant to assess the immediate and long-term consequences of coronavirus disease on the reproductive system of men and their hormonal status AIM: To study of the effect of COVID-19 on the male reproductive system and hormonal status. MATERIALS AND METHODS: The study included the findings of examination and treatment of 62 men aged 22 to 45 years (mean age: 38.3 ± 3.2 years) who had COVID-19 confirmed by PCR testing within 3-6 months prior to the study. Sixteen (25.8%) men had severe disease, and 46 (74.2%) men suffered from moderate one. All patients enrolled in the study had spermogram parameters, mixed antiglobulin reaction (MAR) test findings and total plasma testosterone levels were within the reference values before the disease. These parameters were determined for all patients after recovery at 6 and 12 months. RESULTS: Six months after the disease, significant spermatogenesis disorders, manifested by a decreasing concentration and/or mobility and/or the number of normal forms of spermatozoa, leukospermia, were observed in 14 of 16 (87.5%) patients in the severe disease group and in 16 of 46 (34.7%) patients with moderate severity disease (p 0.05). Total plasma testosterone levels were decreased in all 16 (100%) patients in the severe group and in 32 of 46 (69.6%) patients in the moderate group (p 0.05). Within 12 months after the disease, significant disorders in the main spermogram parameters were observed in 5 of 16 (31.2%) patients with severe coronavirus disease, and in 4 of 46 (8.7%) patients with moderate coronavirus (p 0.05). A decrease in total plasma testosterone levels occurred in 10 of 16 (62,5%) men of the severe disease group and in 4 of 46 (8.7%) men with moderate disease (p 0.05). CONCLUSIONS: Our findings demonstrate the negative impact of COVID-19 on male fertility and hormonal status. The coronavirus severity mainly determines the rate, intensity and duration of spermatogenesis disorders and hypogonadism manifestations that occur after it.

Leptin fragment modulates the stimulatory effects of chorionic gonadotropin on testicular steroidogenesis in a model of diet-induced obesity in rats

Leptin, secreted by adipose tissue, indirectly stimulates the activity of GnRH-producing neurons of the hypothalamus and thus regulates the functional activity of the hypothalamic-pituitary-testicular (HPT) axis. As is known, the obesity is accompanied by systemic hyperleptinemia and impaired leptin transport in the central nervous system, which limits the use of full-length leptin as a drug. It was previously shown that intranasally administered leptin fragment MA-[D-Leu4]-OB3 (LF) enhances the steroidogenic effect of human chorionic gonadotropin (hCG) in rats fed a standard diet. An even more urgent task is to assess its effect on testicular steroidogenesis in conditions of obesity, which reduces reproductive functions in men. The aim of the work was to study the ability of LF (200 μg/kg, intranasally, 3 days) to modulate the effect of hCG (10 IU/rat, subcutaneously, once) on testicular steroidogenesis in rats with obesity induced by a high-fat/high-carbohydrate diet (HFHCD), and also to evaluate influence of the GnRH receptor antagonist cetrorelix (ANT, 75 µg/kg, subcutaneously, 3 days) on the effects of LF. Male Wistar rats were used for the study and received HFHCD for 20 weeks. In obese rats, the level of the luteinizing hormone (LH) receptor in the testes was reduced and the expression of the Cyp11a1 gene, encoding the steroidogenic enzyme cytochrome P450scc, was compensatory increased. LF administration enhanced the effect of hCG on the testosterone level in the blood and the expression of the Star gene, encoding the cholesterol transport protein StAR, which indicates the ability of LF to positively modulate the activity of the HPT axis in obesity. Co-administration of ANT and LF, on the contrary, reduced the stimulating effect of hCG on testosterone levels and Star gene expression, which may be due to the testicular effects of LF. Our data indicate the ability of LF to influence various components of the male gonadal axis under conditions of diet-induced obesity.

Impact of adalimumab on erectile dysfunction, sperm parameters and hormonal profile in male psoriasis patients: a six-month observational study.

Psoriasis, a chronic inflammatory skin disease, is associated with systemic complications that extend beyond cutaneous lesions, including cardiovascular risks and sexual dysfunction. Erectile dysfunction (ED) is notably more prevalent in male psoriasis patients, likely driven by both systemic inflammation and psychological stress. Adalimumab (ADA), a tumor necrosis factor-alpha (TNF-α) inhibitor, has been shown to effectively reduce psoriasis severity, but its effects on sexual and reproductive health remain underexplored. This study investigates the impact of ADA on erectile function, sperm parameters, and hormonal profiles in male psoriasis patients. This six-month prospective observational study included 33 biologic-naïve male patients aged 18-50 years with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] > 10). Patients received ADA according to standard clinical protocols. Erectile function was assessed using the International Index of Erectile Function (IIEF-5). Sperm parameters, including ejaculate volume, sperm concentration, total sperm count, motility, vitality, and morphology, were analyzed following World Health Organization (WHO) 2010 criteria. Hormonal profiles (testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and prolactin) were measured via standardized assays. Statistical analyses were performed using paired t-tests or Wilcoxon signed-rank tests, with p-values < 0.05 considered significant. ADA significantly improved erectile function, as the mean IIEF-5 score increased from 21.3 ± 2.2 to 22.2 ± 1.9 (p = 0.03). The percentage of patients with ED decreased from 51.5% at baseline to 36.4% post-treatment (p < 0.001). Progressive sperm motility and vitality showed statistically significant improvement post-treatment (p = 0.02 and p = 0.04, respectively), while other sperm parameters remained unchanged. Total testosterone levels significantly increased from 3.4 ± 0.4 ng/ml to 3.5 ± 0.4 ng/ml (p = 0.02), while LH, FSH, estradiol, and prolactin levels showed no significant changes. The anti-inflammatory properties of adalimumab, through the inhibition of TNF-α, not only reduce psoriasis severity but also appear to exert positive effects on male sexual and reproductive health. Our study demonstrated significant improvements in erectile function, sperm motility, vitality, and testosterone levels in male psoriasis patients after adalimumab therapy. These findings suggest that beyond its role in controlling psoriatic skin lesions, adalimumab may help mitigate the systemic inflammatory burden that contributes to sexual dysfunction and impaired spermatogenesis. Future long-term studies are essential to further explore the sustained impact of TNF-α inhibition on male fertility and reproductive outcomes.

Assessment of Sex Hormones (FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone) of Pulmonary Tuberculosis Patients

Background: Tuberculosis (TB) is a one of the major global health problems ranking as the eighth leading cause of death in low- and middle-income countries. This study was carried out to evaluate the Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Prolactin, Estrogen, Progesterone and Testosterone of pulmonary tuberculosis patients in Edo State. Objectives: The objectives of the study are to assess the FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone levels of Pulmonary Tuberculosis (PTB) patients compared with control, hormonal levels of PTB patients of new case, 2 months and 6 months therapy compared with control, hormonal levels of PTB patients in relation to gender and hormonal levels of PTB patients in relation to age. Material and methods: A total of 120 samples were used in this study comprising PTB new cases (30), PTB 2 months therapy (30), PTB 6 months therapy (30) and Control (30) respectively. FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone were measured by Enzyme-Linked Immunoassay Test (ELISA). The results were presented using tables as mean ± standard deviation. Statistical analysis was done using one-way Analysis of Variance (ANOVA) and the student’s t-test. Significant difference was accepted at p&lt;0.05. Results: The results obtained showed that the FSH (mIU/ml) of new case subjects, 2 months on therapy, 6 months on therapy and control were 13.42±3.58, 11.38±3.04, 6.52±2.57 and 8.71±3.15; LH (mIU/ml) was 10.43±2.95, 8.32±2.44, 5.21±2.23 and 6.05±2.44; prolactin (µg/L) was 10.17±4.04, 9.47±2.56, 10.11±6.74 and 12.96±7.09; estrogen (pg/ml) was 35.97±9.27, 41.50±12.65, 57.60±17.46 and 64.97±29.24, progesterone (ng/ml) was 0.18±0.05, 0.25±0.06, 0.40±0.10 and 0.37±0.08; and testosterone (ng/ml) was 2.49±0.95, 2.48±1.46, 4.00±2.92 and 4.32±3.84 respectively. Conclusion: In conclusion, there was significant difference (p&lt;0.05) in the FSH, LH, Prolactin, Estrogen, Progesterone and Testosterone of the subjects in the different groups compared with control. FSH, LH, Prolactin, Estrogen and Progesterone were significantly higher (p&lt;0.05) in female subjects compared with male subjects, while Testosterone was non-significantly (p&gt;0.05) higher in male subjects compared with female subjects.

Assessing the Impact of Ghee, Olive Oil and Margarine on Male Rabbit Fertility and Reproductive Hormones.

In the present investigation, the impact of natural ghee, olive oil and synthetic margarine on the fertility parameters of male rabbits was evaluated by examining semen quality, fertility hormones, antioxidant markers, lipid profile, and liver and kidney functions. Eighty male rabbits were randomly allotted into four groups (20 rabbits each, four replicates/group). The basal diet supplemented the control group; the margarine group was fed a 10% margarine diet, the ghee group was fed a 10% ghee diet, and the olive oil group was fed a 10% olive oil diet. In the margarine group, the semen quality parameters, total testosterone levels, free testosterone, luteinizing hormone (LH) and antioxidant enzyme levels as catalase showed a significant reduction compared to other groups. At the same time, they were enhanced in ghee and olive oil groups. A substantial increase of triglyceride (TAG), low-density lipoprotein (LDL) and cholesterol, with a decrease of high-density lipoprotein (HDL) levels, were observed in the margarine group contrasted to ghee and olive oil groups. The ghee and the olive oil-treated group showed strong immunoreactions of androgen, FSH, LH receptors and mild caspase 3 in testicular tissue compared to the margarine-treated group. Finally, histopathological examination of rabbit testicular tissue showed proliferation of basal spermatogenic cells, increased luminal spermatid of seminiferous epithelium, and proliferation of interstitial cells in normal interstitial tissue in the ghee and olive oil treated group. Still, it showed severe vacuolation and necrosis in the basal luminal seminiferous epithelium and congestion of blood vessels in the margarine group. This present study revealed that the health influence of olive oil and ghee is better than margarine on male fertility parameters.

High 11-ketotestosterone linked to shorter time to castration resistance in recurrent non-metastatic prostate cancer.

The contribution of 11-oxygenated androgens to the progression of lethal prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the androgen receptor agonist 11-ketotestosterone (11KT), could serve as a potential predictor of the onset of castration resistant prostate cancer (CRPC). We used mass spectrometry to quantify 11-oxygenated androgens in post-operative plasma samples acquired from 145 patients who subsequently received androgen deprivation therapy (ADT) for biochemical recurrence (BCR) and achieved castrated testosterone (T) levels. Kaplan-Meier survival analyses and multivariable Cox models were used to investigate relationships between steroids and CRPC. Of 145 patients, 31 developed CRPC with a median time to CRPC of 57 months. 11-oxygenated androgens levels were unaffected by ADT, which stands in contrast to the observed changes in T and other steroids. 11KT was the most abundant androgen but was not linked to clinical features. Kaplan-Meier analysis revealed that 11KT levels above the median of 273 pg/mL were associated with a shorter time to CRPC (P = 0.03). In multivariable analyses, this was supported with an adjusted hazard ratio of 2.17 (95% confidence interval (CI) 0.99-4.71; P = 0.05). 11KT is a key component of the hormonal profile predictive of earlier onset of CRPC. Enhancing our understanding of the specific role of 11KT in the progression to CRPC could help optimize hormonal therapy for castration sensitive PCa and CRPC patients.

Resveratrol improves follicular development in PCOS rats by inhibiting the inflammatory response and pyroptosis of granulosa cells.

Chronic inflammation is a key characteristic of polycystic ovary syndrome (PCOS) and is associated with follicular dysplasia in PCOS. PCOS patients treated with 1000mg resveratrol (RES) daily for 3months showed significant improvement in menstrual cycle regularity compared to the placebo group. This investigation explores potential impact of RES on a rat model of PCOS. Sprague-Dawley (SD) rats were subjected to a 30-day letrozole/high-fat diet interventions for PCOS model establishment, followed by RES intervention (20mg/kg/d) for an additional 30days. RES intervention mitigated obesity, estrous cycle irregularities, and ovulation disorders while decreasing serum testosterone and lipopolysaccharide (LPS) levels in PCOS rats. Concurrently, inflammatory markers (TNF-α, NLPR3, IL-6,) and pyroptosis-related markers (GSDMD, cleaved-Caspase-1, IL-1β, IL-18) were downregulated. Additionally, KGN cells (a human granulosa-like cell line) were treated with LPS and RES for in vitro assays. It was observed that RES (15μM) significantly reduced ROS production and downregulated inflammatory cytokine expression in LPS-intervened KGN cells. Additionally, RES downregulated the expression levels of pyroptosis-related factors (GSDMD and cleaved-Caspase-1) and attenuated IL-18 and IL-1β secretion in LPS-induced KGN cells. Furthermore, RES intervention improved the pyroptosis-associated morphology of KGN cells after LPS treatment. In conclusion, RES may restore follicular development in PCOS rats by inhibiting inflammation and NLRP3/GSDMD/Caspase-1-mediated pyroptosis of ovarian granulosa cells, providing new insights into potential therapeutic approaches for PCOS.

Precocious Puberty in Boys with NR0B1 Variants

Precocious puberty (PP) requires appropriate management to prevent short adult height, psychosocial issues, and other adverse outcomes. Genetic diagnosis potentially improves the management of PP. Pathogenic NR0B1 variants, which typically cause X-linked adrenal hypoplasia congenita, can also affect gonadal function. While boys with NR0B1 variants usually exhibit hypogonadotropic hypogonadism during adolescence, previous reports have suggested that minipuberty, a physiological transient activation of the hypothalamic–pituitary–gonadal axis during infancy, occurs in these patients and can persist beyond a typical duration. In rare cases, NR0B1 variants cause PP. PP associated with NR0B1 variants has unique features such as early onset and high serum testosterone levels that are often disproportionate to testicular size. Three underlying mechanisms have been proposed for the association between PP and NR0B1 variants: (1) adrenocorticotropic hormone (ACTH)-dependent, (2) gonadotropin-dependent, and (3) ACTH- and gonadotropin-independent mechanisms. The factors contributing to PP vary among cases. Determining the underlying mechanisms is crucial for adopting appropriate therapeutic strategies to control PP. However, as the detailed molecular networks mediating these mechanisms are largely unclear, further research is needed to pave the way for a more effective and personalized management of patients with PP associated with NR0B1 variants.

Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility

Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Conclusion: Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol’s impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol’s effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis.

Long-term effects of sub-chronic exposure to L-NAME on reproductive system of male rats.

Nω-nitro-l-arginine methyl ester (L-NAME) has been utilized as a nitric oxide synthase antagonist for many years in both basic and clinical research settings to assess its therapeutic potential. Though a number of studies have shown the effect of L-NAME on testicular function, the information regarding the reversibility of these effects upon L-NAME withdrawal is limited. In the present study, male rats (68-80days old) divided randomly into three groups received different doses of L-NAME, i.e. 20mg/kg bw (L20) and 10mg/kg bw (L10) in drinking water, and drinking water only (control) through oral gavage daily for three weeks. The rats were monitored for and sacrificed after 60days of L-NAME treatment termination. The animals had a significantly higher (p < 0.01) mean blood pressure compared to control. Aberrant histological changes were observed in the testes of L-NAME-treated rats. A significant reduction (p < 0.05) in the sperm count and an increase in abnormal sperm morphology (p < 0.05) was observed in L-NAME treated rats. Moreover, the spermatogenic cycle was found to be altered in L-NAME treated rats. No change was observed in serum estradiol levels, while serum testosterone levels were significantly increased (p < 0.05) in L10 and L20 animals. The intra-testicular testosterone was increased significantly (p < 0.01) in L20 animals. A significant decrease (p < 0.05) in superoxide dismutase activity was observed in L20 animals. The sub-chronic exposure to L-NAME resulted in higher mean arterial blood pressure and long-term testicular tissue damage, affecting sperm quality and spermatogenesis.

Testosterone mediates life-history trade-offs in female mammals.

Hormones mediate life-history trade-offs. In female mammals, such trade-offs have been studied predominantly in the contexts of oestrogen, progesterone and prolactin. We evaluate the hypothesis that prenatal and postnatal testosterone levels structure and regulate trade-offs in females involving components of reproduction and survival. This hypothesis is predicated on the observation that testosterone confers competition-related and survival-related benefits, but also reproduction-related costs, to female mammals. The hypothesis is supported by field and laboratory data from diverse non-human animals, and data from healthy women. Most broadly, relatively low testosterone level in females has been associated with earlier, faster and higher offspring production, greater attractiveness to males, and reduced dominance or competitiveness, whereas higher testosterone level is associated with delayed and reduced reproduction but increased dominance, status, aggression, and resource accrual. The magnitude of testosterone-mediated trade-offs is expected to depend upon the strength of female-female competition, which represents some function of species-specific ecology, behaviour and mating system. Testosterone-associated trade-offs have, until now, been virtually ignored in studies of female life history, reproductive physiology, evolutionary endocrinology, and female-limited disease, probably due to researcher biases towards conceptualizing androgens as hormones with effects mainly restricted to males.

Lactobacillus Helveticus Improves Controlled Cortical Impact Injury-Generated Neurological Aberrations by Remodeling of Gut-Brain Axis Mediators.

Considerable studies augured the potential of gut microbiota-based interventions in brain injury-associated complications. Based on our earlier study results, we envisaged the sex-specific neuroprotective effect of Lactobacillus helveticus by remodeling of gut-brain axis. In this study, we investigated the effect of L. helveticus on neurological complications in a mouse model of controlled cortical impact (CCI). Adult, male and female, C57BL/6 mice underwent CCI surgery and received L. helveticus treatment for six weeks. Sensorimotor function was evaluated via neurological severity score and rotarod test. Long-term effects on anxiety-like behavior and cognition were assessed using the elevated-zero maze (EZM) and novel object recognition test (NORT). Brain perilesional area, blood, colon, and fecal samples were collected post-CCI for molecular biology analysis. CCI-operated mice displayed significant neurological impairments at 1-, 3-, 5-, and 7-days post-injury (dpi) and exhibited altered behavior in EZM and NORT compared to sham-operated mice. However, these behavioral changes were ameliorated in mice receiving L. helveticus. GFAP, Iba-1, TNF-α, and IL-1β expressions and corticotrophin-releasing hormone (CRH) levels were elevated in the perilesional cortex of CCI-operated male/female mice. These elevated biomarkers and decreased BDNF levels in both male/female mice were modified by L. helveticus treatment. Additionally, L. helveticus treatment restored altered short-chain fatty acids (SCFAs) levels in fecal samples and improved intestinal integrity but did not affect decreased plasma levels of progesterone and testosterone in CCI mice. These results indicate that L. helveticus exerts beneficial effects in the CCI mouse model by mitigating inflammation and remodeling of gut microbiota-brain mediators.

Protective effects of Juglans regia oil on lead acetate-induced reprotoxicity in rats: an antioxidant, histological and computational molecular study.

Lead (Pb) is a metal that affects many body systems, primarily the male reproductive system. This study aimed to examine the phytochemical profiling and beneficial effects of Juglans regia oil (JRO) in alleviating lead-induced reprotoxicity-associated oxidative injury in rats. Adult male Wistar rats were randomly divided into four groups as follows: control group received no treatment, Pb group was exposed to 0.344 g kg-1 bw of Pb acetate, Pb + JRO group was co-treated with Pb plus walnut oil (0.9 g kg-1 bw) and JRO group received walnut oil only. Pb-treated rats showed significantly decreased gonado-somatic index, count and viability of sperm. Testosterone levels decreased in Pb-treated animals. Besides, Pb disrupted the oxidative/antioxidative status, the plasmatic lipase activity and testicular Pb content. Furthermore, Pb produced testis histopathological features, especially cell degeneration, atrophy and tubular disarrangement. Co-treatment with JRO was found to be effective for recovering the increased testicular oxidative damage-associated histological features in the Pb group. This was supported by the in silico modeling results. The in silico analyses revealed that JRO compounds bound androgen receptor and RAC-alpha serine/threonine kinase with high affinities, which together with pharmacokinetic properties and molecular interactions satisfactorily support the beneficial in vivo findings in the Pb + JRO group of rats. © 2024 Society of Chemical Industry.

Abstract A007: Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients

Abstract Background: Prostate cancer (PCA) is the second most prevalent cancer globally and the fifth leading cause of cancer-related mortality. However, effective prognostic biomarkers for metastatic PCA remain lacking. Recent research highlights the role of microRNAs (miRNAs) in regulating cancer stem cells (CSCs) and influencing tumour progression across various cancers. Therefore, in this we investigated the effects of miR-141 and miR-145 expression on the metastatic PCA of CSCs and assessed their potential role as biomarkers for metastatic PCA prognosis. Methods: The expression levels of miR-141 and miR-145 were quantified using real-time qPCR. Flow cytometry was employed to assess the levels of prostate cancer stem cells (PCSCs) in tissue samples from patients with localized (non-metastatic) and metastatic PCA. Results: Our findings revealed a significant increase in miR-141 expression, accompanied by elevated levels of CD44^high/CD24^low and CD133^high, in metastatic PCA compared to localized PCA. Conversely, reduced miR-145 expression was associated with enhanced stemness characteristics, as indicated by increased CD44^high/CD24^low and CD133^high levels, in metastatic PCA compared to localized PCA. Additionally, prostate-specific antigen (PSA) and testosterone levels exhibited a significant rise (p&amp;lt;0.001), while apoptosis rates decreased in both localized and metastatic PCA compared to localized PCA. Conclusions: The collective findings of this study suggest that miR-141 and miR-145, in conjunction with CSC markers, hold promise as diagnostic and prognostic tools for PCA. They may also be valuable for detecting minimal residual disease and improving therapeutic strategies for managing metastatic PCA. Citation Format: Kamla Kant Shukla, Gautam Ram Choudhary. Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A007.

Effects of time-of-day resistance training on muscle strength, hormonal adaptations, and sleep quality during Ramadan fasting

ObjectivesWe investigated the timing of resistance training (RT) during Ramadan fasting (RF) on muscle strength, hormonal adaptations, and sleep quality.MethodsForty healthy and physically active male Muslims (age = 25.7 ± 5.6 years, body mass = 85.1 ± 17.5 kg, height = 175 ± 9 cm, BMI = 28.3 ± 5.7 kg/m2) were enrolled in this study and 37 completed pre and post-tests. Subjects were randomly allocated into two experimental groups. Group 1 (FAST, n = 20) completed an 8-week whole-body RT in the late afternoon (between 16 h and 18 h) while fasting. Group 2 (FED, n = 20) completed the similar RT protocol compared with FAST at night (between 20 h and 22 h). The following parameters were analyzed at various time-points: 2 weeks before the start of RF (T0), on the 15th day of Ramadan (T1), on the 29th day of Ramadan (T2), and 21 days after the last day of RF (T3) where both groups were in a fed state. One-repetition maximum tests (1-RM) were conducted for the squats (1-RMSQ), the deadlift (1-RMDL) and the bench press (1-RMBP). Sleep quality was assessed using the full Pittsburgh Sleep Quality Index (PSQI). Blood samples were taken to determine cortisol, testosterone and IGF-1 levels. Additionally, acute hormonal responses were evaluated before (BF), immediately after (AF), and 30 min after a RT session (AF-30 min) at T0, T1, T2, and T3.ResultsSignificant group-by-time interactions were identified for 1-RMSQ (p = 0.001; effect size [ES] = 0.43) and 1-RMDL (p = 0.001; ES = 0.36). Post-hoc tests indicated significant 1-RMSQ (p = 0.03; ES = 0.12) and 1-RMDL (p = 0.04; ES = 0.21) improvements from T0-T2 for FED. Additionally, significant group-by-time interactions were observed for the chronic effects on cortisol (p = 0.03; ES = 0.27) and testosterone levels (p = 0.01; ES = 0.32). Post-hoc tests indicated significant increases of cortisol levels among FAST at T1 and T2 compared to T0 (p = 0.05; ES = 0.41, p = 0.03; ES = 0.34) and a significant increase in cortisol levels in FED at T1 (p = 0.05; ES = 0.29) and T2 (p = 0.04; ES = 0.25). However, the observed increase was lower compared to FAST. Post-hoc tests also indicated significant increases of testosterone only among FED at T2 (p = 0.04; ES = 0.31). A significant group-by-time interaction was found for the acute effect of exercise on cortisol level (p = 0.04; ES = 0.34). The cortisol level immediately after RT was higher in FAST only at T1 (p = 0.03; ES = 0.39) and T2 (p = 0.05; ES = 0.22) compared with T0. No significant group-by-time interactions were identified for sleep quality (p = 0.07; ES = 0.43).ConclusionMuslims can safely practice RT during RF. However, training in a fed state during Ramadan might be more effective than during fasted state for the enhancement of maximal strength with better hormonal responses observed.

The role of anti-aging approaches in managing hypogonadism in sedentary older males

IntroductionWith thirty percent of the world’s population not getting enough exercise, Worldwide, physical inactivity ranks as one of the most common causes of premature mortality. Rapid drops in physical activity, decreased mobility, and early morbidity are aging characteristics. As the population over 80 continues to rise, aging raises the danger of age-related illnesses and changes in hormone release.AimUnderstanding the aging process is useful in developing pharmacological therapies and identifying therapeutic targets for age-related testosterone deficiency. Therefore, this study’s purpose is to present a thorough evaluation of the effects of anti-aging strategies on testosterone levels in older, inactive men.MethodsA literature search was completed for clinical and preclinical studies published in English between 2014 and 2024 related to age, sedentary life, testosterone, and anti-aging strategies.ResultsA sedentary lifestyle and low testosterone are linked to a vicious cycle. A sedentary lifestyle lowers testosterone levels, which leads to depression, exhaustion, low energy, and weakened bone and muscle strength. These effects exacerbate the detrimental consequences of aging and physical inactivity. Anti-aging techniques can prevent and treat age-related diseases, including calorie restriction, a balanced diet, regular exercise, weight control, diabetes management, and quitting smoking. Regular exercise raises total testosterone, free testosterone, and muscle steroidogenesis. In older men, testosterone replacement treatment increases bone density, cholesterol, protein synthesis, strength, erectile function, sexual desire, and general cognitive performance. However, some studies suggest dehydroepiandrosterone supplementation may provide health improvements without negative effects, potentially reversing arterial aging and reducing cardiovascular disease risk.ConclusionThis article evaluates the prospects for anti-aging procedures to assist in reducing the adverse effects of aging and physical inactivity in men.

BS O02 - Impact of Bariatric surgery on Obesity Indices and Reproductive Hormones: A Prospective Study in Morbidly Obese Women

Abstract Background Obesity, defined by a BMI of 30 kg/m² or higher, is influenced by genetics, socio-economic, and cultural factors. Genetic predispositions affect metabolism and energy regulation, while environmental factors like sedentary lifestyles and poor food environments worsen obesity. Obesity disrupts hormonal balances, impacting sex hormone levels and menstrual cycles, leading to infertility in women. This hormonal imbalance affects oocyte quality and ovulation. Bariatric surgery offers significant weight loss and metabolic improvements, enhancing reproductive hormone profiles and insulin sensitivity. Our study explores how sleeve gastrectomy affects BMI and hormone levels, aiming to understand its impact on obesity management and reproductive health. Method This prospective observational study examines the effects of laparoscopic sleeve gastrectomy on reproductive hormones and ovarian function in 32 morbidly obese women, adhering to Helsinki Declaration ethics. Participants, aged 18-50 with no menopause or chronic illness, consented to the study. Exclusions included those with polycystic ovary syndrome, recent reproductive organ surgery, or recent infertility medications. The study assessed changes in BMI, antral follicles, anti-Müllerian hormone, and reproductive hormones before surgery and at 6 and 12 months post-surgery. Blood samples and transvaginal ultrasounds were conducted preoperatively and at 6 and 12 months postoperatively to monitor outcomes. Results The study involved participants with an average age of 33 and a mean BMI of 42.12. Significant changes were observed post-sleeve gastrectomy at 6 and 12 months (p &amp;lt; 0.001). At 6 months, BMI decreased by 9.24 units, AMH levels dropped from 3 to 2.5 ng/mL, and antral follicle counts in both ovaries declined. By 12 months, BMI decreased by 16.47 units, AMH levels fell to 2 ng/mL, and antral follicle counts further reduced. Hormonal changes included increases in FSH, LH, and estradiol, while SHBG levels rose, and free testosterone levels decreased significantly. Conclusion Individual hormone responses to weight loss and surgery necessitate personalized obesity treatments. Tailoring surgical approaches and care to hormonal profiles can optimize outcomes and reduce complications. Monitoring AMH levels post-surgery can offer insights into reproductive effects, aiding clinical management and counseling for women with obesity-related infertility. We highlight the significant impact of sleeve gastrectomy on physiological parameters in obese individuals, especially regarding reproductive health and metabolic regulation. The findings enhance understanding of the changes associated with bariatric surgery and its potential benefits for metabolic and reproductive health.

Poor semen quality is associated with impaired antioxidant response and acute phase proteins and is likely mediated by high cortisol levels in Brucella-seropositive dromedary camel bulls.

Brucellosis in dromedary camel bulls leads to either temporary or permanent loss of fertility. Camel brucellosis is associated with both orchitis and epididymitis. However, the clinical signs of camel brucellosis are not clear as those in cattle. Therefore, this study aimed to diagnose camel brucellosis based on a serological screening using Rose Bengal plate test (RBPT) followed by competitive ELISA. To understand the impact of brucellosis on camel bull fertility, this study aimed to examine the semen characteristics, evaluate the testicular histopathology, examine hormonal profile, antioxidants and acute phase proteins (APP). A total of 150 mature bulls were used in this study. Blood samples were collected for serological, hormonal, and biochemical analysis. This study revealed that 6.6% and 7.3% of the examined bulls were Brucella-seropositive using RBPT and competitive ELISA, respectively. The Brucella-seropositive dromedary bulls showed poor semen quality, pathological changes orchitis, and lower testosterone. Moreover, our findings showed a higher cortisol level, and significant impairments in the measured APP and antioxidants in Brucella-seropositive bulls. In conclusion, the Brucella-seropositive dromedary bulls showed lower fertility due to poor semen quality and lower testosterone levels. Such lower fertility is likely mediated by high cortisol levels, and impaired APP and antioxidants' defense response.

Post-pubertal management of undescended testes from the malignancy risk point of view: a systematic review

Background Undescended testes (UDT) is a condition where one or both testes is absent in the scrotum. The general age recommendation in which the treatment should be performed is before 18 months old due to the infertility risk and malignancy in later life. In post-pubertal UDT, the current guideline recommends orchiectomy; however, the strength rating of this recommendation is weak. Therefore, this study aimed to provide a systematic review of post-pubertal UDT treatment, focusing on the malignancy risk point of view. Methods A systematic search was performed using PubMed, Wiley Online Library and the Cochrane Library up to 5 March 2023. Any study with either post-pubertal orchiectomy or orchidopexy in patients with UDT and reporting the testicular malignancy was included. The exclusion criteria were studies with lack of information of UDT correction time, no history of correction and the full text wasn’t available. The data collected were the occurrence of testicular malignancy in post-pubertal UDT patients corrected with any method. Quality and bias assessment was assessed with Newcastle-Ottawa scale and Joanna Briggs Institute tools. Results Seven articles (three case reports and four observational studies) were reviewed with a total of 42 patients who underwent post-pubertal correction of either unilateral or bilateral UDT. The correction age ranged from 13 to 34 years old, with follow-up of 48.7–252 months. Among those who developed malignancies, the most common were seminoma, teratoma and carcinoma in situ of the testes. In addition, this study was able to propose an algorithm for post-pubertal UDT treatment strategy. Conclusions The scarce resource was the main limitation of this study. Nevertheless, this review showed that post-pubertal UDT management should be tailored individually. Several factors that should be considered include the condition of the contralateral descended testis, UDT location, serum testosterone level, patient’s age, comorbidities, and interest in fertility.