Asian journal of andrology最新文献

It is essential to use high-quality adipose-derived stem cells (ADSCs) for clinical applications. The functional characteristics of ADSCs differ in the presence of various health conditions. Specifically, recent studies of the therapeutic effects of ADSCs from individuals with diabetes and no erectile dysfunction (NED-ADSCs), ADSCs from those with diabetes and erectile dysfunction (ED-ADSCs), and normal ADSCs have generated conflicting results. Therefore, we aimed to provide evidence for the clinical utility of ADSCs. Diabetes mellitus (DM) was induced in rats by the intraperitoneal injection of streptozotocin (STZ; 40 mg kg-1) following 4 weeks of high-fat diet feeding. After 12 weeks, erectile dysfunction was confirmed using the apomorphine (80 µg kg-1) test, and those with diabetes mellitus-related erectile dysfunction (DMED) were randomly assigned to treatment groups. Each group was administered 1 × 106 allogeneic ADSCs by injection into the corpus cavernosum; then, erectile function and penile histology were evaluated 28 days later. Of the three ADSCs types injected, normal ADSCs exhibited the strongest proliferation and differentiation capabilities. Following ADSCs treatment, there was an increase in smooth muscle cell number and a higher muscle-to-collagen fiber ratio. The expression of neuronal nitric oxide synthase (nNOS) in the dorsal nerve significantly increased. In addition, proteomic analysis revealed that heat shock protein expression was very low in the diabetic rats, but upregulated by stem cell therapy, which may represent a mechanism for the beneficial effects of ADSCs. Therefore, men with diabetes should consider the early preservation of ADSCs to help prevent the onset of erectile dysfunction (ED).

Prostate cancer is a malignant tumor posing significant threats to the health of men worldwide. In advanced stages, it frequently progresses to castration-resistant prostate cancer, which is characterized by complex mechanisms and poor prognosis. In such cases, conventional treatments have limited effectiveness. However, the emergence of radionuclide therapy has provided new hope. Lutetium-177-labeled prostate-specific membrane antigen (177Lu-PSMA), currently the most promising radioligand in clinical research, received approval from the U.S. Food and Drug Administration (FDA) in 2022. This review comprehensively summarizes recent advancements, efficacy assessments, and safety evaluations of 177Lu-PSMA therapy. Additionally, we analyze its current limitations and suggest future research directions for PSMA-targeted radioligand therapy (RLT). Undoubtedly, 177Lu-PSMA-617 is transforming metastatic castration-resistant prostate cancer (mCRPC) treatment. However, challenges remain regarding its potential standardization for use in non-mCRPC cases, the optimal treatment sequence, standardized imaging/molecular biomarkers, and toxicity management, all of which require further prospective validation.

Lifestyle factors have been linked to decreased sperm quality and may influence the prevalence of Ureaplasma urealyticum infection. This study aims to clarify the relationships among Ureaplasma urealyticum infection, lifestyle factors, and semen quality. In this retrospective study, 2668 male partners of infertile couples who underwent fertility evaluation at the Center for Reproduction and Genetics of The First Affiliated Hospital of USTC (Hefei, China) between April 2020 and March 2023 were enrolled. Participants were assessed for semen parameters, clinical characteristics, and lifestyle factors. Of the 2668 participants, 659 (24.7%) participants were positive for Ureaplasma urealyticum . Body mass index (BMI), smoking, and sexual frequency (>2 times per week) were significantly higher in the Ureaplasma urealyticum -positive group than those in the Ureaplasma urealyticum -negative group. After adjustment for potential confounders, smoking (odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.02-1.49, P = 0.03) and sexual frequency (more than twice per week; OR = 1.41, 95% CI: 1.04-1.91, P = 0.03) remained associated with Ureaplasma urealyticum infection. Regarding semen parameters, ejaculate volume was significantly lower in the Ureaplasma urealyticum -positive group ( P = 0.002); however, the prevalence of abnormal semen quality did not differ between the two groups. Logistic regression and restricted cubic spline analysis revealed no significant associations between poor semen quality and Ureaplasma urealyticum infection. In conclusion, Ureaplasma urealyticum infection was associated with certain lifestyle factors but not with semen quality. Further research is required to elucidate the underlying mechanisms and to evaluate potential interventions.

As immunotherapy continues to push the envelope, it has had transformative success in malignancies such as melanoma and lung cancer. However, in contrast to these cancers, implementing immunotherapy in prostate cancer (PCa) still presents considerable difficulties. PCa itself is not sensitive to immunotherapy. The low response rate of PCa to immunotherapy cannot be attributed to a single mechanism. Instead, it results from the interplay of multiple adverse factors. These include the tumor's inherently low immunogenicity and the highly immunosuppressive properties of its tumor microenvironment. Taken together, these features create a "perfect storm" that severely limits the efficacy of immunotherapy. In this review, we comprehensively assess the latest advances in PCa immunotherapy, encompassing cancer vaccines, immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cell (CAR-T) therapy, and various combination regimens. We also summarize their limited efficacy observed in clinical practice to date. Furthermore, we explore the underlying mechanisms contributing to the limited effectiveness of immunotherapy in PCa, with a focus on intrinsic molecular features, the immunosuppressive microenvironment, and key signaling pathways. Through an in-depth review of previous studies, we aim to provide a theoretical foundation and strategic guidance to enhance the effectiveness of immunotherapy for PCa and to facilitate the development and translation of more targeted and effective immunotherapeutic interventions.

Male obesity-associated secondary hypogonadism (MOSH) affects metabolic and reproductive health. We evaluated the efficacy of laparoscopic sleeve gastrectomy (LSG) on the remission of MOSH and testosterone concentrations and examined the association between weight loss and changes in testosterone concentrations. In this retrospective study, 304 male patients with obesity who underwent LSG at the Center for Obesity and Hernia Surgery, Huashan Hospital, Fudan University (Shanghai, China) between October 2022 and December 2024 were screened. Metabolic and hormonal parameters were evaluated at baseline and at 6 months, 12 months, and 24 months post-LSG. The primary outcome was the remission of MOSH. Secondary outcomes were changes in total testosterone concentrations and free testosterone concentrations, and their correlations with the percentage of total weight loss (TWL%). Among 304 screened patients, 212 were diagnosed with MOSH and 186 were included (mean ± standard error [s.e.]; age: 33.1 ± 0.6 years; body mass index: 43.0 ± 0.5 kg m -2 ). MOSH remission rates at 6 months, 12 months, and 24 months post-LSG were 81.4%, 79.7%, and 89.5%, respectively, accompanied by a substantial increase in total testosterone and free testosterone concentrations. TWL% (mean ± s.e.) reached 28.2% ± 0.9%, 34.4% ± 1.2%, and 32.3% ± 2.2% at the respective time points. Linear mixed models showed significant positive correlations between TWL% and total testosterone and free testosterone concentrations after surgery (both P < 0.001). LSG induced the remission of MOSH and restored testosterone concentrations. Sustained weight loss is pivotal in driving endocrine recovery, suggesting that LSG is effective for managing MOSH.

Hypospadias is a common congenital malformation of the male external genitalia, with severe cases presenting considerable surgical and long-term challenges. Despite the clinical importance of severe hypospadias demonstrated by prolonged hospital stays, repeated surgeries, and substantial costs, the genetic etiology of severe hypospadias remains incompletely understood, particularly in diverse populations. To determine the molecular basis, we performed whole-exome sequencing (WES) on 30 Chinese patients from southeastern China with confirmed 46,XY karyotypes. Our analysis identified clinically relevant genetic variants, including single-nucleotide variants (SNVs) and copy number variations (CNVs), with subsequent phenotypic correlation. Clinically relevant genetic variants were identified in 33.3% (10/30) of cases, including novel SNVs in gonadal regulators (nuclear receptor subfamily 5 group A member 1 [NR5A1] c.1344dupC/c.244+1G>T and SRY-box 3 [SOX3] c.1273G>C), morphogenetic modulators (GLI family zinc finger 3 [GLI3] c.4731delA and aristaless-related homeobox [mARX] c.644C>G), and syndromic genes (patched domain containing 1 [PTCHD1] c.667G>A and euchromatic histone lysine methyltransferase 1 [EHMT1] c.3081C>T). Additionally, recurrent CNVs at 22q12.3 and a novel CNV exon 18 deletion in myelin regulatory factor (MYRF) and 18q11.2 were identified. Mutation carriers showed a significantly higher frequency of cryptorchidism (40.0% vs 5.0%, P < 0.01) and a higher prevalence of ≥3 associated malformations (80.0% vs 35.0%, P < 0.05) than non-carriers, highlighting genotype-phenotype correlations. The 33.3% diagnostic yield tripled conventional estimates, demonstrating WES efficacy in identifying SNVs and CNVs in severe phenotypes. These findings reveal the genetic heterogeneity of severe hypospadias and support WES utility in uncovering novel variants and structural genomic alterations.

Although genetic factors contribute significantly to male infertility, the underlying mechanisms remain incompletely understood. Coiled-coil domain-containing protein 113 (CCDC113) encodes a coiled-coil domain-containing protein critical for the assembly of cilia and flagella. Using whole-exome sequencing, we identified biallelic CCDC113 mutations in two unrelated families affected by oligoasthenoteratozoospermia. The mutations (c.901A>C; p.K301Q and c.404A>C; p.E135A) cosegregated with infertility phenotypes and were associated with defective sperm flagella. Functional analyses demonstrated that these mutations led to less stable CCDC113 protein and severely disrupted axonemal structures in spermatozoa from our three human patients. We generated Ccdc113 knockout mice, which recapitulated the human infertility phenotypes, including abnormal sperm morphology, impaired motility, and defective spermatogenesis. Importantly, one patient achieved successful pregnancy by intracytoplasmic sperm injection, highlighting the translational potential of genetic diagnostics. These findings suggest that CCDC113 is essential for male fertility and contribute to the understanding of the genetic landscape of infertility, offering novel insights into its diagnosis and management.

Currently, there are limited data to support the association between sulfur dioxide (SO2) exposure and semen quality. Here, we analyzed nine elements including vanadium (V), chromium (Cr), iron (Fe), copper (Cu), cobalt (Co), nickel (Ni), manganese (Mn), selenium (Se), and strontium (Sr) in seminal plasma of 738 participants using inductively coupled plasma mass spectrometry (ICP-MS). Each participant was assigned an average SO2 exposure of 0-90 days preceding semen collection. Associations were determined using multivariable linear models, susceptible exposure windows were identified via distributed lag nonlinear models (DLNM), and indirect effects and effect modification were examined based on mediation and interaction analyses. Notably, SO2 exposure was negatively associated with sperm concentration (β: -0.07; 95% confidence interval [CI]: -0.13 to -0.01; P = 0.02), total sperm count (β: -0.09; 95% CI: -0.15 to -0.03; P < 0.01), progressive motility (β: -0.04; 95% CI: -0.07 to -0.01; P = 0.02), and total motility (β: -0.03; 95% CI: -0.07 to -0.01; P < 0.01), but positively associated with sperm abnormal morphology (β: 0.27; 95% CI: 0.12 to 0.42; P < 0.01). DLNM identified a susceptibility window during spermiogenesis (lags 37-69 days). Se was positively associated with sperm concentration (β: 0.34; 95% CI: 0.23 to 0.45; P < 0.01) and total sperm count (β: 0.28, 95% CI: 0.16 to 0.40; P < 0.01), mediating 23.6% and 14.6% of the effects of SO2, respectively. A significant interaction between SO2 and Ni was detected in sperm abnormal morphology (β: 0.28; 95% CI: 0.05 to 0.51; P = 0.02). These results indicate that SO2 exposure may reduce semen quality, and this effect may be mediated by Se and modified by Ni.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis significantly associated with urethral stricture disease (USD), particularly affecting the genitalia in both sexes. While topical corticosteroids remain the first-line therapy for LS, their efficacy for deep urethral involvement is limited. Surgical intervention, primarily urethroplasty utilizing buccal mucosa grafts or lingual mucosa grafts, is often required for LS-associated USD but is associated with risks of recurrence and complications. This review explores the etiology, highlighting the roles of immune dysregulation, genetic factors, and the resulting fibrosis. Furthermore, we emphasize the emerging potential of urethral tissue engineering, which uses scaffolds seeded with progenitor or stem cells, as a promising approach for reconstructing complex LS-related strictures, although clinical translation remains limited. Future research should focus on optimizing tissue engineering solutions.