Diagnosis and prognosis of testicular cancer remain challenging due to lack of reliable diagnostic markers. While lipidomic alterations have been explored in other cancers, their application to testicular cancer is limited. Lipidomics may offer valuable insights, as lipid changes in blood can reflect tumor development. The goal was to assess the lipid profile changes in testicular tissue (with and without tumor) and plasma, from testicular cancer patients compared with healthy controls, to identify key differences. In this study, untargeted C18 RP-LC-MS lipidomics approach was used to assess the plasticity of lipid profile in testicular tissue (with and without tumor) and plasma, from testicular cancer patients. Principal component analysis revealed a clear discrimination of the samples. Malignant tissue showed significant upregulation of several phosphatidylcholine (PC) and lyso-phosphatidylcholine (LPC) species mainly esterified to saturated and monounsaturated fatty acids (FAs), while phosphatidylinositol, phosphatidylserine, and phosphatidylglycerol species containing polyunsaturated FA were downregulated when compared with nontumor tissues from the same patients. Plasma samples from patients with testicular cancer showed increased levels of PC, LPC, and some sphingomyelin (SM) species, and decreased triacylglycerol (TG) and diacylglycerol (DG) species when compared with healthy controls. Five lipid species, TG 52:6, TG 56:7, phosphatidylethanolamine (PE) P-40:3/PE O-40:4, PC 42:3, and PC P-37:2, showed consistent differential expression across both tissue and plasma. These findings highlight the modification of lipid metabolism in testicular cancer, offering novel insights into the disease's pathophysiology and supporting the potential of lipids as diagnostic markers for its detection and monitoring.

Erectile dysfunction (ED) is a prevalent condition with important vascular and systemic implications. Although air pollution has been linked to multiple chronic diseases, its association with ED remains insufficiently explored. To investigate the association between long-term exposure to multiple ambient air pollutants and the risk of ED among Taiwanese men. We conducted a retrospective nationwide cohort study using the National Health Insurance Research Database from 2000 to 2013. Ten-year cumulative exposures to 11 pollutants-sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), particulate matter <10 µm (PM10), particulate matter <2.5 µm (PM2.5), nitrogen oxides (NOX), nitrogen monoxide (NO), nitrogen dioxide (NO2), total hydrocarbons (THC), nonmethane hydrocarbons (NMHC), and methane (CH4)-were estimated by linking residential postal codes. The outcome was incident ED (Ninth Revision of the International Classification of Diseases, Clinical Modification 302.72 or 607.84). Cox regression models adjusted for demographics, comorbidities, medications, ambient temperature, season, and short-term pollutant levels were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During follow-up, 4936 participants (1.16%) developed ED. Each 1-SD increase in SO2, CO, O3, PM10, PM2.5, NOX, NO, NO2, THC, NMHC, and CH4 was associated with increased ED risk (adjusted HRs 1.45-2.65; p < 0.001 for all). Conversely, O3 exposure was inversely associated with ED (HR 0.45; 95% CI 0.44-0.46). These associations remained consistent across age strata. Our findings suggest that chronic exposure to most ambient air pollutants may contribute to ED, potentially through vascular, endocrine, and inflammatory pathways, while O3 may exhibit paradoxical protective effects. Long-term exposure to multiple air pollutants is associated with an elevated risk of ED among Taiwanese men, highlighting air pollution as a potential modifiable environmental risk factor for men's sexual health.

Erectile dysfunction (ED) significantly impacts quality of life. For patients unresponsive to conservative treatments, penile prosthesis implantation represents an effective solution with high satisfaction rates. However, the complexity and sensitive nature of the procedure often generate multiple patient concerns. Artificial intelligence (AI) chatbots such as ChatGPT are increasingly used for medical information, although concerns remain regarding accuracy and misinformation. This study aimed to evaluate the clarity, accuracy, and clinical appropriateness of ChatGPT's responses to frequently asked questions (FAQs) on penile prosthesis surgery. Fifteen representative FAQs were identified from patient forums and educational platforms. Questions were submitted to ChatGPT (GPT-4, November 2024) in a single session. A panel of seven expert urologists evaluated responses using a four-point Likert scale across four domains: clarity, medical accuracy, relevance, and risk of misinformation. All responses achieved mean scores above 3, indicating overall clinical acceptability. The highest ratings were observed for relevance (3.40 ± 0.54) and clarity (3.37 ± 0.57). Slightly lower scores were reported for medical accuracy (3.19 ± 0.67) and risk of misinformation (3.18 ± 0.59). A strong positive correlation was found between clarity and relevance (ρ = 0.80), while medical accuracy correlated with lower misinformation risk (ρ = 0.77). ChatGPT provides generally clear, relevant, and clinically acceptable responses for patient education in penile prosthesis surgery, although minor clarifications are often required. It may serve as a supportive tool to complement traditional counseling but cannot replace physician-patient communication, which remains essential for individualized care and informed decision-making.

Male hypogonadotropic hypogonadism is a complex condition with a multifactorial etiology. Although testosterone replacement therapy (TRT) is the only approved treatment for male hypogonadism, clomiphene citrate (CC) is often used as an off-label treatment. The present study was conducted to objectively compare clinical outcomes, including adverse effects in patients receiving clomiphene citrate and testosterone replacement therapy. This is a retrospective study of data collected through the Veterans Administration Informatics and Computing Infrastructure. We identified 364,976 patients with hypogonadisma or infertility. After one-to-one propensity matching, we identified 2518 individuals in both clomiphene citrate and testosterone replacement therapy treatment groups. Outcomes included new diagnoses of fractures, osteoporosis, polycythemia, thrombosis, hypertension, pulmonary embolism, coronary artery disease, and cerebrovascular accidents, which were evaluated relative to the two treatments. Survival was plotted for both treatments and analyzed by Kaplan‒Meier statistics. The incidence of various complications was significantly lower after clomiphene citrate relative to testosterone replacement therapy treatment, including new-onset hypertension (6.04%vs. 10.48%), cerebrovascular accident (0.52%vs. 1.43%), coronary artery disease (1.51%vs. 2.26%), polycythemia (1.07%vs. 2.22%), and osteoporosis (1.15%vs. 2.07%). All-cause mortality was also significantly lower in the clomiphene citrate group (1.83%) relative to testosterone replacement therapy group (10.13%). CC increased testosterone levels relative to baseline in a physiological manner. TRT was associated with increased mortality relative to CC. Rates of stroke, coronary artery disease, hypertension, osteoporosis, and polycythemia were also greater in patients receiving TRT. Our results also indicate that CC increased testosterone levels relative to baseline in a physiological manner.

Male infertility is a prevalent clinical condition, with approximately one-third of cases classified as idiopathic, frequently stemming from impaired spermatogenesis because of dysregulated gene expression. Chromodomain helicase DNA-binding (CHD) proteins are central chromatin remodelers that orchestrate this epigenetic regulation. For instance, smoking-induced hypermethylation of the CHD5 gene promoter is associated with impaired semen parameters. This review aims to summarize the roles and mechanisms of CHD proteins in spermatogenesis, explore their relationship with male infertility, and discuss their potential as diagnostic and therapeutic targets. A comprehensive literature review was conducted to synthesize current findings on the expression and function of CHD proteins across different stages of spermatogenesis. Research has shown that CHD proteins are expressed in the testis and play crucial roles in multiple stages of spermatogenesis, from spermatogonial stem cell (SSC) maintenance to spermatid maturation, making them promising targets for understanding and treating male infertility. CHD proteins represent important epigenetic regulators in spermatogenesis and may serve as valuable biomarkers or therapeutic targets for male infertility.

The main functions of testes are sperm production and androgen secretion in testicular befitting microenvironment. Excessive level of the reactive oxygen species (ROS) from metabolism and cellular events can lead to oxidative stress (OS) and ferroptosis, which injure the functions of mitochondria and endoplasmic reticulum (ER) of testicular cells, leading to the impaired spermatogenesis and spermiogenesis, as well as insufficient androgen. Our previous studies have shown that peroxiredoxin 4 (Prdx4) is a vital ER-located protector against endoplasmic reticulum stress (ERS) in ovarian granulosa cells. In this study, we explored whether Prdx4 played a beneficial role in testes, and the potential application value in male reproduction. Prdx4 knockout mice and Prdx4-/y Leydig cells were established using CRISPR/Cas9 system, the natural adult (9 weeks) mice, aging (9 months) mice, and wild-type MLTC-1 cells were used as control. To further investigate the protective effect of Prdx4 in the adult mice, the testicular 43°C water-bath was used to induce an OS model. The male Prdx4-/y mice aged over 9 months showed the age-related pathology of seminiferous tubule, the increased OS and ERS, and the decreased fertility. The adult Prdx4-/y mice under heat stress manifested increased levels of OS, including almost 1.5-fold rise in 4-hydroxynonenal (4-HNE) and 8-hydroxy-2'- deoxyguanosine (8-OHdG), higher ferroptosis, and poorer fertility. Prdx4-/y Leydig cells showed a higher level of ferroptosis after hydrogen peroxide treatment. ACSL4 increased by 18.6% while COX2 increased by 13.5%, and the expressions of GPX4 and SLC7A11 decreased by 49.2% and 24.3%, respectively. Increased levels of ferroptosis in MLTC-1 leads to mitochondria-derived OS and apoptosis, which can be partially restored by deferoxamine and overexpressing SLC7A11. We concluded that Prdx4 as a protective factor plays a critical role in preserving spermatogenesis by alleviating testicular OS and ferroptosis, and that Prdx4 may be known as a potential target in mitigating the adverse effects of natural aging and OS injury.

The influence of paternal Hepatitis B virus infection on reproductive outcomes after in vitro fertilization or intracytoplasmic sperm injection is still debated. While differences in sperm-oocyte interaction duration and intensity between in vitro fertilization and intracytoplasmic sperm injection may lead to divergent viral exposure effects. Nevertheless, research specifically examining these differences remains limited. To evaluate how various insemination techniques influence the effects of paternal Hepatitis B virus infection on reproductive outcomes in couples during in vitro fertilization/intracytoplasmic sperm injection treatments. This retrospective study analyzed 37,088 initial frozen-thawed embryo transfer cycles among women without Hepatitis B virus infection from February 2007 to August 2023. Patients were grouped into two categories based on paternal Hepatitis B virus surface antigen status: paternal Hepatitis B virus surface antigen positive (Hepatitis B virus surface antigen [+]) and negative (Hepatitis B virus surface antigen [-]) categories. Further stratified analyses were performed according to the insemination method. The primary endpoints were measures of pregnancy and neonatal results. An analysis using logistic regression was conducted to explore the independent link between paternal Hepatitis B virus infection and the specified outcomes. In in vitro fertilization-derived embryos, paternal Hepatitis B virus infection was significantly associated with an elevated risk of miscarriage (adjusted odds ratio 1.55, 95% confidence interval 1.22-1.96), small for gestational age (adjusted odds ratio 1.70, 95% confidence interval 1.12-2.59), and very small for gestational age (adjusted odds ratio 3.07, 95% confidence interval 1.64-5.76) by comparison with controls. No such associations occurred with intracytoplasmic sperm injection-derived embryos. Prior studies have shown inconsistent findings on the effects of paternal Hepatitis B virus infection on these outcomes. This study provides evidence that paternal infection with the Hepatitis B virus independently elevates the risks of miscarriage, small for gestational age, and very small for gestational age births following in in vitro fertilization, but not intracytoplasmic sperm injection. This discrepancy might be due to differences in the extent and duration of oocyte exposure to the Hepatitis B virus. Male Hepatitis B virus infection independently increases the risk of miscarriages and the birth of small for gestational age and very small for gestational age infants after in vitro fertilization embryo transfer, but not after intracytoplasmic sperm injection.

Sperm quality in TGCT patients showed marked variability. Non-seminoma diagnosis appeared less detrimental than seminoma, yet BEP chemotherapy severely impaired sperm parameters, especially in non-seminoma cases. These results highlight the importance of individualized post-chemotherapy monitoring using standard semen analysis, cytometry-based qualitative assessments, and epigenetic profiling of histone modifications to optimize fertility preservation and guide optimal treatment strategies by andrologists.

Testicular germ cell tumors (TGCTs) are the most common malignancies in young men. The clinical management largely relies on classical serum tumor markers. However, these markers offer limited sensitivity and specificity, underscoring the need for more reliable biomarkers. In recent years, members of the miR-371∼373 microRNA (miR) cluster, particularly miR-371a-3p, have emerged as superior alternatives, showing excellent diagnostic performance in various clinical settings. While most of the research efforts regarding miR-371∼373 have focused on its clinical utility, recent studies suggest that miR-371a-3p is more than just a diagnostic marker. In this narrative mini-review, we highlight five recent studies all of which provide novel insights into its broader biological roles. The key issues are as follows: (1) the release of miR-371a-3p from cancer cells is accomplished via extracellular vesicles; (2) the miRNA plays an important role in intercellular communication between tumor cells and the tumor microenvironment. (3) There are strong analogies between the human miR-371∼373 cluster and the murine miR-290∼295 cluster, which support the relevance of the gPAK mouse model for preclinical research. (4) miR-371a-3p contributes to cisplatin resistance in TGCTs, and antagomir-based inhibition of this miRNA might be an emerging potential therapeutic strategy. (5) The detection of miR-371a-3p in serum of pregnant women suggests a functional role in feto-maternal signaling. This concise review aims to bridge the gap between clinical and experimental research, positioning miR-371a-3p as both a superior biomarker and a pivotal molecule in TGCT biology with potential therapeutic implications.

Platelet-rich plasma (PRP) injection into penile plaques is an emerging, investigational approach for treating acquired penile curvature in men with stable-phase Peyronie's Disease (PD). We report preliminary findings from a two-center prospective pilot study. Thirty-eight men with stable PD underwent two PRP injections (≈8mL each), 4weeks apart. PRP was prepared using either double or single centrifugation (2-cycle vs. 1-cycle group). All patients initiated tadalafil 5mg daily and penile stretching with a vacuum device (5-15min/day) 1week after the first injection. Baseline and 3-month follow-up assessments included dynamic penile color doppler-duplex ultrasound (CDDU), International Index of Erectile Function (IIEF), and Peyronie's disease questionnaire (PDQ). Twenty-two patients (57.9%) received 2-cycle PRP; 16 (42.1%) received 1-cycle PRP. Baseline penile curvature was 45° (37-70) in the 2-cycle group and 60° (50-66) in the 1-cycle group, decreasing to 40° (30-50) and 50° (40-56), respectively (p=0.002 and p=0.008). Overall, median curvature decreased from 55° (45-70) to 45° (30-55), with a median reduction of 10° (0-15) (p<0.001). PDQ scores improved significantly in both groups (p≤0.006), while IIEF-EF and CDDU parameters remained unchanged. Plaque diameter showed a non-significant reduction. No treatment-emergent adverse events occurred. PRP injections appear safe and may modestly improve penile curvature and PDQ scores in men with stable-phase PD. However, the observed curvature reduction is insufficient to infer clinically meaningful long-term outcomes. Larger controlled studies are warranted.