Andrology最新文献

Background: Ionizing radiation is widely used in medical diagnostics and cancer therapy, notably radioiodine therapy for thyroid carcinoma. While high or repeated ionizing radiation doses are known to impair male fertility, the impact of clinically relevant single-dose exposures on sperm functional and nuclear integrity is less understood.

Objectives: This study aimed to evaluate the in vitro effects of ionizing radiation doses corresponding to standard therapeutic and diagnostic exposures on human sperm parameters.

Materials and methods: Using a computed tomography scan, ejaculated sperm samples (n = 96) were exposed in vitro to 14 mGy of ionizing radiation (equivalent to single abdominal-pelvic computed tomography scan, n = 35), 70 mGy (five computed tomography scans, n = 39), and 140 mGy (one radioiodine therapy with 3.7 GBq of [131I]iodine, n = 86). For each of the three dose conditions, normozoospermic and non-normozoospermic samples (WHO 2021) were included. Functional (vitality, motility) and nuclear biomarkers (chromatin deprotamination, DNA fragmentation, and sperm telomere length), oxidative stress markers (MDA-TBARS), and capacitation parameters (AMPc concentration, phosphotyrosine profiles, velocity, and acrosome integrity) were assessed against paired controls.

Results: Exposure to 14, 70, and 140 mGy of ionizing radiation induced significant reductions in sperm vitality (p < 0.01 for 14 mGy and p < 0.001 for 70 and 140 mGy), as well as in total and progressive motility (p < 0.001 for 140 mGy). However, sperm vitality and motility values remained within the WHO 2021 reference ranges. Absorbed doses of 70 and 140 mGy increased deprotamination (p < 0.05 and 0.01, respectively). Effect sizes were mostly small, except for a medium to large effect for vitality at the highest dose. DNA fragmentation, telomere length, oxidative stress, and capacitation-associated markers remained unaffected. These effects were consistent across normozoospermic and non-normozoospermic samples.

Discussion and conclusion: Clinically relevant low-doses of ionizing radiation produced modest impairments in sperm functional and chromatin integrity without detectable DNA breakage or oxidative injury. These findings support the relative safety of low-dose therapeutic exposures on mature spermatozoa. This in vitro model also offers a platform for further exploration of sperm radiosensitivity.

Background: Oligoasthenozoospermia is a leading cause of male infertility and has been increasingly associated with the global surge in obesity and exposure to reproductive toxicants. Despite extensive research on each factor individually, their combined pathological effects remain poorly understood.

Objectives: This study aimed to investigate how obesity and reproductive toxicants independently and synergistically impair male reproductive function by establishing and comparing rat models of oligoasthenozoospermia induced by each factor and their combination.

Materials and methods: We constructed three etiologically distinct oligoasthenozoospermia male Sprague-Dawley rat models: a reproductive toxicity model induced by glycosides of Tripterygium wilfordii Hook. f. (GTW), a metabolic dysfunction model induced by a high-fat diet (HFD), and a combined model (HFD + GTW). Animals were randomly assigned and subjected to 12 weeks of treatment. Body weight, metabolic indices, serum sex hormone levels, sperm quality parameters, and histopathological analysis of the testes and epididymis, as well as gut microbiota composition and testicular transcriptome profiles, were systematically evaluated. We also performed quantitative real-time polymerase chain reaction.

Results: Both GTW and HFD independently impaired reproductive function, leading to decreased sperm count and motility, hormonal disturbances, and moderate testicular damage. The combined model exhibited significantly exacerbated reproductive impairment, including extensive spermatogenic cell loss, disrupted testicular architecture, and the lowest sperm quality indices. Multiomics analysis revealed coordinated alterations in gut microbiota composition and testicular transcriptomes, suggesting crosstalk between metabolic and inflammatory signaling pathways. Quantitative real-time polymerase chain reaction confirmed these transcriptomic patterns, showing upregulation of Ahnak, C1r, S1pr1, and Steap4, alongside downregulation of Alkbh7, Tbpl1, Tent5b, and Ldhal6b in the models.

Conclusion: This study successfully establishes reliable rat models that mimic both individual and combined etiologies of oligoasthenozoospermia. The interaction between obesity and GTW-induced reproductive toxicity aggravates testicular injury through metabolic disruption and inflammatory pathways, offering an integrative platform for mechanistic and therapeutic research.

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.

Background: Microdissection testicular sperm extraction is the preferred method for sperm retrieval in men with non-obstructive azoospermia. However, the effects of sperm retrieval quantity and freezing on intracytoplasmic sperm injection outcomes remain incompletely understood.

Objectives: To evaluate the impact of sperm quantity and freezing status on fertilization and cumulative live birth rate following intracytoplasmic sperm injection using microdissection testicular sperm extraction spermatozoa in non-obstructive azoospermia patients.

Materials and methods: We retrospectively analyzed 1394 microdissection testicular sperm extraction-intracytoplasmic sperm injection cycles performed between 2017 and 2022 at a single tertiary center. Sperm retrieval yield was stratified into three groups: sufficient sperm count (> 10 spermatozoa/100 fields), low sperm count (6-10/100), and extremely low sperm count (1-5/100). Fertilization rate (two pronuclei) and cumulative live birth rate were compared across sperm retrieval yield and freezing subgroups. Multivariable regression and interaction models assessed the independent and combined effects of sperm quantity and freezing status.

Results: Fertilization and cumulative live birth rate declined significantly with reduced sperm counts (two pronuclei: 53.6%→32.2%; cumulative live birth rate: 49.8%→21.8%; p < 0.001). Frozen spermatozoa yielded comparable outcomes to fresh spermatozoa overall, but in the extremely low sperm count group, frozen spermatozoa were associated with a significantly lower cumulative live birth rate than fresh spermatozoa (12.3% vs. 29.3%; p = 0.015). Interaction analysis confirmed this adverse effect (OR = 0.39; 95% CI 0.16-0.95; p = 0.038). No significant freezing effect was observed in the other groups.

Conclusion: Sperm retrieval quantity is an important predictor of intracytoplasmic sperm injection success in men with non-obstructive azoospermia. Freezing generally does not affect outcomes, but may significantly reduce live birth rates when sperm availability is extremely limited. Prioritizing the use of fresh spermatozoa in such cases may improve clinical outcomes.

Background: Erectile dysfunction (ED) and acute coronary events are closely linked, yet the trajectory of ED following percutaneous coronary intervention (PCI) remains incompletely understood. The residual SYNTAX score (RSS) quantifies incomplete revascularization and is an established prognostic tool in cardiology; however, its role in erectile function recovery after myocardial infarction (MI) is unclear.

Objectives: To evaluate whether RSS predicts recovery of erectile function after MI treated with PCI.

Materials and methods: In this prospective cohort study, 82 men aged 40-70 years who underwent PCI for MI were evaluated. ED was assessed using the International Index of Erectile Function-5 (IIEF-5) at baseline (after recovery from PCI, reflecting erectile functions before MI), and at 3 and 6 months. ED was defined as an IIEF-5 score ≤21. Patients were stratified according to RSS (<8 vs. ≥8). Anxiety (sexual-fear subscale) and depressive symptoms (BDI-II) were also assessed.

Results: ED was present in 57.3% of patients at baseline, increased to 68.7% at 3 months, and decreased to 37.3% at 6 months. At 6 months, mean IIEF-5 scores improved significantly in men with RSS <8 (from 17.9 to 21.2; p < 0.001), but not in those with RSS ≥8 (from 17.2 to 16.3; p = 0.314). While severe ED remained largely unchanged over time, mild-to-moderate ED demonstrated the greatest improvement. Anxiety independently predicted ED at 3 months (OR 1.223, p = 0.049). At 6 months, RSS ≥8 independently predicted persistent ED (OR 3.22, p = 0.033), with moderate discriminatory accuracy (AUC 0.72).

Conclusion: RSS ≥8 may identify men at increased risk for persistent ED after MI. The differential recovery patterns suggest that reversible functional impairment may predominate in milder forms of ED, whereas persistent severe ED may reflect more extensive systemic and penile vascular disease. Early recognition of anxiety and targeted sexual counseling may support erectile recovery following PCI.

Background: Testicular germ cell cancer (TGCC) is the most frequent malignancy in young men of reproductive age. According to guidelines, semen cryopreservation should be performed prior to orchiectomy. Lack of time and local facilities as well as mental pressure are challenges in terms of fertility preservation before surgery.

Objective: This study aims at comparing semen parameters before and after orchiectomy in TGCC patients.

Materials and methods: We prospectively recruited 25 patients with TGCC who performed semen cryopreservation at our Centre. Study participation included a pre-surgery cryopreservation (T0) and post-surgery visits within 8 weeks (T1) before any further gonadotoxic therapies. Testicular ultrasound, hormone values, and total sperm count (TSC), sperm concentration, sperm motility and vitality were included for analysis. The primary endpoint was the change in TSC (ΔTSC) from T0 to T1. p < 0.05 was considered statistically significant.

Results: Histopathology of the 25 patients revealed 16 seminomas and nine non-seminomas. Median age was 30 years (interquartile range [IQR]: 28-35; mean age ± standard deviation [SD] 30.96 ± 5.86). TSC was higher at T1 compared with T0 in seven patients, while 18 patients showed a lower TSC at T1. Median TSC for all patients was 52.8 Mill/ejac. (IQR: 26.8-88.8) before-and 26.5 Mill/ejac. (IQR: 4.4-82.6) after orchiectomy showing an overall decrease. Wilcoxon signed rank test however did not result in a statistically significant decrease in TSC (p = 0.083). There was a decline in sperm concentration (p = 0.004) and in motility (a+b) (p = 0.004).

Discussion: Because we found an overall decrease in sperm quality post-surgery, we suggest that semen cryopreservation in TGCC patients should always be performed before orchiectomy. However, in some patients higher TSC was observed after orchiectomy. Thus, an individualized additional potential for cryopreservation in selected patients post-surgery can be discussed. We consider our findings a starting point for a prospective multicenter study to validate the obligation for pre-surgical cryopreservation and to identify subgroups who might benefit from additional post-surgery cryopreservation.

Background: The most prevalent solid tumors in young men are testicular germ cell tumors (TGCTs), and embryonal carcinoma is the most common subtype among non-seminomatous germ cell tumors (NSGCTs). Despite the excellent cure rates of cisplatin-based chemotherapy, resistance develops in 15%-30% of patients with metastatic cancer, which results in a poor prognosis. The overexpression of the High Mobility Group A2 (HMGA2) protein has been linked to treatment resistance and cancer aggressiveness. It is well known that this protein promotes carcinogenesis.

Objective: The purpose of this work was to investigate the functional role of HMGA2 in EC cell migration, survival, and proliferation, focusing on its role as a potential therapeutic target in cisplatin-resistant ECs.

Materials and methods: We employed human EC cell lines EP2102 and GCT27, as well as the cisplatin-resistant (CisR) versions of these cell lines that were produced by prolonged drug treatment. siRNA transfection was used to suppress HMGA2 expression. Growth curve and colony formation tests were used to measure cell proliferation. Apoptosis was assessed by Annexin V staining followed by flow cytometry, cell cycle distribution was analyzed by flow cytometry, and cell migration was detected by Boyden Chamber Assays.

Results: In both parental and resistant EC cell lines, HMGA2 knockdown markedly decreased proliferation. After HMGA2 knockdown, flow cytometric analysis revealed S phase arrest. Apoptosis was significantly elevated, especially in cells that were resistant to cisplatin. In addition, all HMGA2-depleted cell lines showed decreased migration. These impacts were true for both the GCT27 and EP2102 models.

Discussion: The data suggest that HMGA2 is necessary to preserve the EC cells' malignant characteristics. Its silencing interferes with several cancer-related functions, including motility, survival, and cell cycle progression. These results indicate HMGA2's participation in chemoresistance mechanisms and are consistent with its role in other solid cancers.

Conclusion: Our results indicate a role of HMGA2 in the EC, because its inhibition reduces cell malignant characteristics, and may represent a viable therapeutic target to improve the prognosis of CisR TGCTs.

Introduction: 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.

Material and methods: Thirty-eight men with stable PD underwent two PRP injections (≈8 mL each), 4 weeks apart. PRP was prepared using either double or single centrifugation (2-cycle vs. 1-cycle group). All patients initiated tadalafil 5 mg daily and penile stretching with a vacuum device (5-15 min/day) 1 week 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).

Results: 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.

Conclusions: 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.

Background: The extracellular calcium concentration is important for sperm function, maturation, and survival, however, studies exploring the link between seminal calcium and reproductive function have reported inconsistent findings.

Objectives: To investigate the association between seminal calcium levels and semen quality in both healthy and infertile men.

Materials and methods: A total of 301 young men from the general Danish population who participated in a study of semen quality, and 228 infertile men who were supplemented with calcium (500 mg) + cholecalciferol (300,000 IU bolus followed by 1400 IU daily), or placebo in a randomized controlled trial were included. Each man underwent a physical examination, routine semen analysis, analysis of calcium concentrations in the seminal fluid, and blood sampling for assessment of PTH, testosterone, estradiol, inhibin B, and AMH.

Results: In young men from the general population, sperm concentration was higher in those within the highest seminal calcium quartile (Q4: 9.0-19.2 mmol/L) compared with the lowest (Q1: 1.3-4.7 mmol/L; 53.0 million/mL vs. 31.0 million/mL, p = 0.010). Accordingly, infertile men in Q1 had the lowest sperm concentration (e.g., 6.6 vs. 22.5 million/mL in Q3), but also fewer progressively motile spermatozoa (p = 0.030). Supplementation with calcium and cholecalciferol did not affect seminal calcium concentration (p = 0.33), however, infertile men who experienced an increase in their seminal calcium concentrations > 30% at the end of intervention had a higher sperm concentration (p = 0.048) and total sperm count (p < 0.001) compared with baseline. There was a weak positive correlation between longitudinal changes of seminal calcium and serum estradiol (r = 0.17, p = 0.016).

Conclusions: Lower seminal calcium concentration is associated with poorer semen quality but was not influenced by calcium supplementation. Future research should focus on uncovering possible regulators, for instance, estrogens.

Trial registration: ClinicalTrials.gov no. NCT01304927 (registered February 28, 2011).