Andrology最新文献

Background: 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.

Objectives: 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.

Material and methods: 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.

Results: 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.

Discussion: 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.

Conclusions: 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.

Background: Advanced paternal age is associated with reduced male fertility and testicular dysfunction. Among the molecular regulators involved in aging, SIRT1, a NAD⁺-dependent deacetylase, plays a pivotal role in maintaining oxidative balance and cellular homeostasis. Although the age-associated decline in SIRT1 levels is well established, the extent to which this reduction underlies testicular dysfunction and the specific proteomic alterations linked to it remain to be elucidated.

Objective: This study aimed to determine whether testicular SIRT1 insufficiency contributes to testicular aging by promoting changes in the proteomic landscape and impairing male reproductive function.

Materials and methods: We employed a Sirt1⁺/^- mouse model that mimics the partial SIRT1 decline observed during aging. Comparative analyses were conducted across wild type, aged wild type, and Sirt1⁺/^- males. We assessed reproductive performance, testicular histology, sperm quality, and embryo development. In parallel, we performed proteomic profiling of testicular tissue to identify molecular pathways affected by aging and SIRT1 insufficiency.

Results: Sirt1⁺/^- males exhibited marked reproductive impairments, including reduced fertility, compromised embryo development, sperm morphological abnormalities, and increased testicular tubule degeneration. Proteomic analysis revealed substantial remodeling in both aged and Sirt1⁺/^- testes, with overlapping alterations affecting proteins involved in oxidative stress responses, proteostasis, and chromatin regulation. Moreover, several proteins with recognized anti-aging functions were undetectable in both aged and Sirt1⁺/^- models yet consistently expressed in wild-type testes. This deregulation reinforces the notion that testicular SIRT1 insufficiency recapitulates key features of the aging testis.

Discussion: Our findings indicate that partial loss of SIRT1 is sufficient to trigger proteomic and functional hallmarks of testicular aging. In particular, we identified specific proteomic signatures linked to subfertility, including the loss of key capacitation-related proteins regulated by SIRT1 in the testis, a pattern also observed in aged animals, which may represent a mechanistic model of SIRT1-governed fertilization failure.

Background: Testicular germ cell tumours (TGCTs) are the most common type of tumour diagnosed in young men, and reliable non-invasive biomarkers are crucial for clinical management. MicroRNAs (miRNAs) from the miR-371-373 cluster have recently been identified as novel and more sensitive serum biomarkers than the conventional protein-based markers. However, few studies have looked at the expression of the miR-371-373 cluster in tumour tissue.

Objectives: To investigate the expression of miR-371a-3p and miR-373-3p in testicular tumour tissue and compare it with matched serum levels.

Materials and methods: We used single-molecule in situ hybridisation (smISH) on tumour tissue from 33 patients-30 with TGCT and three with the precursor lesion, germ cell neoplasia in situ (GCNIS)-of whom 20 had paired pre-orchiectomy serum samples. We validated the smISH using RT-qPCR on tumour tissue from 12 patients.

Results: Both miR-371a-3p and miR-373-3p were positive in all tumour tissue samples except for teratoma. Also, patients with TGCT that were negative in serum for either miR-371a-3p (n = 4) or miR-373-3p (n = 6) showed positive expression in their tumour tissue. The expression levels varied across tumours, with miR-373-3p generally showing higher expression than miR-371a-3p. All samples with GCNIS were positive, both when adjacent to tumour tissue (n = 6) and without an invasive component (n = 3).

Discussion: Although our study only included 33 cases, we covered all TGCT components. In situ expression patterns indicate that miR-373-3p has a diagnostic value independent of miR-371a-3p.

Conclusion: All non-teratomatous TGCT and GCNIS tissue showed expression of miR-371a-3p and miR-373-3p, and the lack of detection in serum consequently seems to be related to technical sensitivity.

Background: Chronic kidney disease (CKD) frequently coexists with hypothalamic-pituitary-gonadal dysfunction, yet the exposure-response shape linking kidney function, testosterone, and outcomes remains unclear.

Methods: Based on data from five cycles of the National Health and Nutrition Examination Survey (NHANES) and the UK Biobank (UKBB), we used multivariate logistic regression models and linear regression models to explore the associations between total testosterone levels and CKD as well as estimated glomerular filtration rate (eGFR). Subsequently, we plotted restricted cubic splines (RCS) of testosterone levels against the risk of CKD and the eGFR. Finally, we further verified the association between total testosterone levels and eGFR based on the kidney transplant cohort.

Results: Across both populations, lower eGFR was revealed to be associated with lower total testosterone in an approximately linear fashion. RCS identified an inflection around the "borderline low" range of about 300-400 ng/dL; below that, CKD risk rose steeply, indicating a nonlinear, threshold-like risk pattern. The logistic regression analysis based on the public databases also indicated that CKD would reduce testosterone levels (NHANES: β = -17.98, 95% CI: -29.54, -6.420, p-value = 3.4 × 10^-3; UKBB: β = -12.25, 95% CI: -14.84, -9.661, p-value = 1.9 × 10^-20), but it had no effect on estradiol. In the validation cohort of kidney transplant recipients, total testosterone increased significantly after transplantation, whereas estradiol showed no parallel rise.

Conclusion: Our findings demonstrate a clear linear-threshold relationship between declining eGFR and reduced testosterone levels, and show that testosterone significantly increases after renal function recovery in kidney transplant recipients.

Background: Familial clustering of testicular germ cell tumour (TGCT) is well-established, whereas the risk of non-testicular cancer among relatives remains inconsistent across studies.

Objective: To evaluate the overall and site-specific cancer risk among first-degree relatives and grandparents of TGCT patients compared to cancer-free controls.

Materials and methods: We enrolled 1453 subjects from two andrology centres: 628 TGCT patients, 367 oncohaematological (OH) malignancy patients, and 458 cancer-free controls undergoing vasectomy. Family cancer history was collected through standardized questionnaires documenting cancer occurrence and type in first-degree relatives and grandparents, categorizing malignancies into 16 specific groups.

Results: Positivity for family history of cancer was significantly higher in the TGCT cohort compared with controls (p < 0.001), whereas no significant increase was observed in the OH cohort. Conversely, analyses based on tumour rates (total number of cancers) revealed significantly higher tumour burden in both TGCT and OH cohorts compared to controls (p < 0.001). Site-specific analysis in TGCT patients' relatives showed significantly higher risk of TGCT (OR: 6.11, 1.83-20.39), pancreas (OR: 9.05, 2.17-37.66), thyroid (OR: 6.32, 1.45-27.55), uterine (OR: 4.82, 1.08-21.44) and urinary tract cancers (OR: 3.07, 1.43-6.58). Both TGCT and OH relatives showed a significant risk for breast, gastrointestinal and lung cancer.

Discussion: We observed notable familial clustering of cancers, not limited to TGCT but spanning several malignancies. Many of the observed associations involve cancers within the Lynch syndrome spectrum, suggesting TGCT as a potential atypical manifestation of Lynch-associated tumorigenesis. Nonetheless, the familial aggregation may also reflect gene-environment interactions and susceptibility loci related to hormone-dependent pathways, as evidenced by the elevated risks of breast and uterine cancers in TGCT families. One of the major limitations of our study, like many others relying on familial data, is the potential for recall bias in patient-reported family histories.

Conclusions: Our study demonstrates a significant familial cancer risk in TGCT patients, underscoring the importance of detailed family history collection and the need for further studies to clarify the contributing genetic and environmental determinants.

Background: Erectile dysfunction (ED) is a multidimensional condition commonly affecting men living with HIV. The structured interview of erectile dysfunction (SIEDY) is the only validated tool assessing organic, relational, and psychological factors contributing to ED, while dynamic penile color Doppler ultrasound (dPCDU) is a reliable method for evaluating vascular causes of ED.

Objectives: This monocentric cross-sectional study aims to assess the reliability of the SIEDY questionnaire in determining the underlying causes of ED in young men living with HIV.

Materials and methods: Young men (<50 years) living with HIV, on antiretroviral therapy for at least the last 12 months, and reporting symptoms of ED were enrolled. The degree of sexual dysfunction was assessed with the International Index of Erectile Function-5 (IIEF-5), while SIEDY was used to explore the pathogenetic components of ED. dPCDU was performed to assess vascular damage in the penile district. Univariate binomial logistic regression models were used to evaluate the association between ultrasound parameters and SIEDY results.

Results: A total of 50 young men living with HIV were enrolled, of whom 40 (80%) had at least one altered SIEDY scale, most frequently Scale 3 (70%). Forty-five (90%) participants presented with at least one abnormal ultrasound parameter, with intima-media thickness being the most common (76%). No correlation was found between ultrasound parameters and the SIEDY Scale 1, while logistic regression identified IMT as the only variable significantly associated with SIEDY Scales 2 (relational) and 3 (psychological).

Discussion and conclusions: SIEDY may have limited reliability in detecting vascular causes of ED in this population, particularly underestimating organic causes. The lack of correlation with objective vascular findings highlights the importance of including tools like dPCDU for vascular assessment in routine clinical evaluations of the ED.

Male infertility affects millions of couples globally, yet its genetic causes often remain unknown. This study investigates the role of loss-of-function variants in SSFA2 in disrupting male fertility. Through clinical analysis of infertile men carrying compound heterozygous SSFA2 mutations and functional studies in germ cell-specific knockout mouse models, we demonstrate that SSFA2 deficiency impairs acrosome formation, sperm head morphology, and calcium signaling. Mutant sperm exhibit disrupted mitochondrial distribution, reduced CatSper channel function, and fail to trigger physiological calcium oscillations in oocytes, leading to fertilization failure. While intracytoplasmic sperm injection (ICSI) can partially rescue fertilization, early embryonic development remains compromised. Our findings establish SSFA2 as a critical regulator of acrosomal biogenesis and sperm function, providing new insights into the genetic basis of male infertility and informing clinical strategies for affected patients.

Background: Testicular germ cell tumours (TGCT) are the most common malignancies among young men and represent a major threat to reproductive health. Both the disease itself and oncological treatments, particularly chemotherapy, can compromise spermatogenesis and semen quality.

Objective: To evaluate sperm qualitative parameters in patients diagnosed with TGCT who underwent orchiectomy, assessed before chemotherapy and at 3 and 6 months post-treatment, to monitor their reproductive health with respect to the type of oncological therapy.

Material and methods: Semen samples from seminoma and non-seminoma patients were analysed before and after chemotherapy. Standard spermiogram, flow cytometry (viability, apoptosis, DNA damage, acrosome integrity), sperm motility clustering, and western blot detection of histone modifications (H4K12ac, H3K9ac, H3K36me3) were used to assess chemotherapy-related sperm alterations.

Results: Before chemotherapy, non-seminoma patients showed higher sperm count and volume than seminoma patients. Chemotherapy, particularly BEP, caused severe impairment, with azoospermia and necrozoospermia observed. Normozoospermia declined rapidly in non-seminoma patients, while seminoma showed milder effects. DNA fragmentation, apoptosis, and acrosome integrity remained unchanged. Notably, histone H4K12ac abundance correlated positively with motility, sperm count, morphology, and DNA integrity.

Discussion: Non-seminoma patients had initially better semen quality, which declined rapidly during chemotherapy. Our findings highlight the need for extended sperm analysis in cancer and pathological conditions. Importantly, sperm quality correlated positively with histone H4K12ac abundance, underscoring its clinical relevance in chromatin regulation and paternal contributions to embryonic development.

Conclusion: 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.