Andrology最新文献

Objective: We aimed to investigate the association of a low serum testosterone concentration with the risk of abnormal glucose metabolism (i.e., prediabetes and type 2 diabetes) in men at a 15-year follow-up.

Study population and methods: In a population birth cohort, men with low testosterone (testosterone < 12.1 nmol/L, n = 136) and normal testosterone concentration (testosterone ≥ 12.1 nmol/L, n = 2555) at age 31 were followed up until age 46. Blood samples were drawn at ages 31 and 46, and an oral glucose tolerance test (n = 1409) was performed at age 46.

Results: Men with low testosterone had significantly greater body mass index and waist circumference than men with normal testosterone at ages 31 and 46 (p < 0.001 in all comparisons). In men with low testosterone, the association with abnormal glucose metabolism was mainly driven by adiposity (p = 0.4 after adjusting for waist circumference). However, the risk remained increased, independently of waist circumference, when comparing the lowest and highest quartiles of testosterone (odds ratio:1.8 [95% confidence interval 1.3-2.7]) or when using testosterone as a continuous variable (odds ratio: 0.97 [95% confidence interval 0.95-0.99]). Between ages 31 and 46, body mass index increased more in men with normal testosterone at age 31 and low testosterone at age 46 than in men with normal testosterone or low testosterone at both ages (p < 0.001). Higher sex hormone binding globulin levels were associated with a lower risk for abnormal glucose metabolism independently of waist circumference (p < 0.001).

Conclusion: Low levels of testosterone and sex hormone binding globulin at age 31 associated with an increased risk of developing abnormal glucose metabolism after 15 years' follow-up. This association was partly independent of adiposity but was linked to waist circumference and weight gain.

Background: Infertility is the inability of a couple to conceive after 12 months of unprotected intercourse. The µ-opioid receptor involved in mediating opioid effects and may be associated with male fertility. µ-Opioid receptors were expressed in testicular tissues and spermatozoa, where they may influence spermatogenesis and sperm motility. miR-339-3p was thought to suppress OPRM1 mRNA expression in neuronal cells following opioid exposure through post-transcriptional modulation. However, its role in male infertility remains unexplored.

Objectives: To investigate the relationship between miR-339-3p expression, OPRM1 mRNA expression, and µ-opioid receptor protein level in spermatozoa of infertile versus fertile men, and to assess their association with semen parameters, oxidative stress, and hormonal profile.

Materials and methods: This case-controlled study was conducted on 45 infertile men and 45 healthy fertile men recruited from andrology outpatient clinic, Mansoura University Hospital. Semen analysis, acrosin activity, oxidative stress markers, and serum hormones levels were evaluated. Relative quantification of miR-339-3p and OPRM1 mRNA expression was quantified using qRT-PCR. µ-Opioid receptor protein levels were measured by enzyme-linked immunosorbent assay technique. Correlation and receiver-operating characteristic analyses were performed.

Results: Infertile men exhibited significantly elevated levels of µ-opioid receptor protein (median: 6.41 ng/mL) compared to fertile controls (5.45 ng/mL, p < 0.001), alongside a marked upregulation of OPRM1 mRNA expression (relative quantification = 4.05 vs. 0.993, p < 0.001), representing approximately a 4.08-fold increase. In contrast, miR-339-3p expression was significantly reduced in the infertile group (relative quantification = 0.538 vs. 1.01, p < 0.001), indicating an approximate 0.53-fold change, or nearly 2-fold downregulation. A significant negative correlation was observed between miR-339-3p and OPRM1 mRNA levels (r_s = -0.704, p < 0.001). Receiver-operating characteristic analysis indicated excellent diagnostic accuracy for OPRM1 mRNA (AUC = 0.916) and miR-339-3p (AUC = 0.914) in differentiating infertile from fertile men.

Conclusions: Downregulation of miR-339-3p and overexpression of µ-opioid receptor are associated with impaired semen quality and oxidative imbalance in infertile men. These molecular markers may serve as potential diagnostic indicators in male infertility, pending further validation.

Background: Lycium barbarum polysaccharide (LBP) has long been recognized as having a wide range of beneficial properties for improving proliferation. However, the protective effects and specific mechanisms of d-galactose-induced testicular dysfunction in reproductively senescent rats are not fully understood.

Materials and methods: A d-galactose-induced senescence model in male rats and a d-galactose-induced TM3 cell model were used to investigate the effects of LBP. The protective effect on testicular spermatogenic function was assessed by histological analysis and SA-β-gal staining. In addition, key calcium signaling pathway alterations involved in LBP were assessed using a multi-omics approach and validated by tissue. Single-cell sequencing data were used to further analyze the cellular heterogeneity of calcium signaling.

Results: LBP significantly improved testicular structure, increased the number of spermatogonia in the seminiferous tubules, and significantly attenuated oxidative stress and testicular apoptosis. In addition, LBP restored the expression of key steroidogenic enzymes, as well as elevated levels of testosterone, follicle-stimulating hormone (FSH), and estradiol (E2), and decreased levels of luteinizing hormone (LH). Mechanistically, LBP regulates key signaling pathways, including calcium homeostasis, Hippo and mTOR pathways, which play important roles in cell growth, apoptosis, and tissue regeneration. Single-cell sequencing data show that calcium signaling is more active in the elderly compared to the young, mainly in Leydig cells, Round Spermatids, and Smooth Muscle Cells. In TM3 cell experiments, the LBP reduced SA-β-gal activity, downregulated aging markers (p16, p21, p53), and restored steroid production function. In addition, LBP regulated the Ca²⁺/CaM/CaMKII signaling pathway, improved calcium homeostasis, and reduced apoptosis in rats and cells.

Conclusion: LBP improves d-galactose-induced testicular spermatogenesis mainly by regulating calcium signaling and metabolic pathways and is closely related to elongating spermatids, round spermatids.

Background: Drug-induced hypogonadism is an underrecognized but significant adverse effect of various medications, contributing to male sexual dysfunction and infertility. Despite its clinical significance, comprehensive studies systematically identifying high-risk drugs remain limited.

Objectives: This study aimed to investigate the potential drugs associated with hypogonadism from FDA Adverse Event Reporting System.

Materials and methods: This study analyzed adverse drug events reported from FDA Adverse Event Reporting System covering the period from the first quarter of 2004 to the third quarter of 2024. Cases related to hypogonadism were identified using standardized Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analyses were conducted using the reporting odds ratio and the Bayesian confidence propagation neural network. Drugs were classified according to Anatomical Therapeutic Chemical classification system and clinical applications. This study utilized FDA Label to determine whether adverse drug events related to male hypogonadism are mentioned on their labels.

Results: We identified 10 classes including 42 drugs that showed positive signals for both reporting odds ratio and Bayesian confidence propagation neural network: anesthetics and analgesics, psychiatric and neurological medications, antineoplastic agents, urological medications, hormonal agents, cardiovascular medications, gastrointestinal medications, bone metabolism modifiers, antiretroviral agents, and other drugs. According to the Bayesian confidence propagation neural network algorithm, 6 drugs were considered to have a high risk of causing hypogonadism, and 11 drugs had medium risk. In addition, 20 drugs did not mention adverse drug events related to male hypogonadism, of which 3 were identified as high risk using the Bayesian confidence propagation neural network algorithm.

Conclusions: This research summarized a list of potential drugs associated with hypogonadism. A clear understanding of the risk and frequency of drug-induced hypogonadism can reduce the likelihood of patients developing the condition.

Background: Current treatments for diabetic erectile dysfunction, such as phosphodiesterase type 5 inhibitors, penile injection, or vacuum erection devices, primarily offer symptomatic relief and do not address the underlying pathophysiology, which involves neural, vascular, and smooth muscle degeneration.

Objectives: This study aimed to evaluate the therapeutic potential of amniotic fluid-derived stem cells in a rat model of diabetic erectile dysfunction by assessing their impact on erectile function and penile tissue regeneration.

Methods: Male Sprague‒Dawley rats were divided into control, diabetic, and amniotic fluid-derived stem cell-treated diabetic groups. Diabetes was induced using streptozotocin (60 mg/kg). Five weeks after intracavernous injection of amniotic fluid-derived stem cells (1 × 10⁶ cells per rat), erectile function, penile nerves, endothelial cells, and smooth muscle cells were evaluated through intracavernous pressure measurements, histological analyses, and cellular senescence assessments using class III β-tubulin (TUBB3), rat endothelial cell antigen, and α-smooth muscle actin markers, respectively, along with β-galactosidase staining.

Results: Amniotic fluid-derived stem cell treatment significantly improved erectile function in diabetic rats, as evidenced by increased intracavernous pressure/mean arterial pressure ratios than untreated diabetic rats (p = 0.0307). Immunofluorescence revealed restoration of neuronal and endothelial markers, while α-smooth muscle actin expression increased and β-galactosidase activity decreased, indicating enhanced smooth muscle integrity and reduced cellular senescence.

Conclusion: Intracavernous amniotic fluid-derived stem cell therapy effectively restores erectile function and mitigates tissue damage in diabetic rats by promoting neurovascular regeneration and reducing senescence, highlighting amniotic fluid-derived stem cells as a promising regenerative therapy for diabetic erectile dysfunction and supporting further pre-clinical and clinical investigations.

Background: Non-obstructive azoospermia (NOA) affects approximately 10% of infertile men and represents a major challenge in assisted reproductive technology (ART). A model that includes histological variants could be helpful in predicting sperm retrieval rate (SRR) after microdissection testicular sperm extraction (mTESE) in patients affected by NOA and without genetic abnormalities OBJECTIVES: To develop and validate a predictive nomogram integrating clinical and histopathological variables to estimate SRR in NOA patients undergoing microTESE.

Material and methods: A multi-center retrospective/prospective cohort study was conducted between 2022 and 2024, enrolling 333 men diagnosed with NOA across six academic centers. Preoperative data, including age, body mass index (BMI), hormonal profile (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone), genetic analysis, and ultrasound-measured testicular volume, were collected. MicroTESE was performed under microscopic guidance with histopathological evaluation. Predictive factors for successful sperm retrieval were analyzed through logistic regression, and a predictive nomogram was constructed and internally validated using bootstrapping techniques. Multi-variate logistic regression was performed to identify independent variables associated with SRR in patients with available final pathology. Therefore, a predictive nomogram was developed and validated using 1000 bootstrap samples.

Results: The overall SRR was 52.55%. Multi-variate analysis identified FSH levels (odds ratio [OR]: 0.97; p = 0.049), maturation arrest (OR: 0.04; p < 0.01), and Sertoli cell-only syndrome (SCOS; OR: 0.03; p < 0.01) as independent predictors of SRR. The predictive nomogram demonstrated good accuracy, with a C-index of 0.75, sensitivity of 73%, specificity of 82%, and overall accuracy of 77% at a cutoff of 0.33.

Discussion: Using preoperative and histology data, we developed a nomogram to predict SR outcomes in patients with NOA undergoing mTESE. Our findings demonstrate that integrating hormonal and histopathological data enhances predictive accuracy of the model, thus providing a valuable tool for preoperative counseling and clinical decision-making in couples presenting with infertility.

Conclusion: This validated nomogram effectively predicts sperm retrieval outcomes in NOA patients undergoing microTESE, facilitating improved patient counseling, informed clinical decisions, and optimized patient selection. Prospective external validation and further model refinement are recommended to enhance generalizability and clinical applicability.