Andrology最新文献

Background: Male factor infertility accounts for up to 50% of couples' inability to conceive. Despite this significant burden, perspectives on male fertility have evolved over millennia, shaped by cultural, medical, and scientific frameworks. Tracing this trajectory illuminates how historical observations laid the foundations for modern andrological science.

Objectives: This scoping review maps the evolution of male fertility research from ancient civilizations through contemporary precision medicine approaches, identifying key paradigm shifts, persistent knowledge gaps, and emerging frontiers in the field.

Methods: Following Arksey and O'Malley's framework, we systematically searched historical medical texts, archaeological records, and biomedical databases (PubMed, Embase, Web of Science) from inception to 2025. Sources encompassing ancient fertility practices, medieval to early modern medical writings, the microscopy revolution, the endocrinology era, and contemporary molecular approaches were included. Data were extracted and synthesized thematically across temporal epochs.

Results: Our review reveals five major paradigm shifts: (i) ancient empiricism (3000 bce to 500 ce) emphasizing humoral balance and dietary interventions; (ii) medieval stagnation with persistence of Galenic theories; (iii) the microscopic revolution (1677-1900) establishing cellular foundations; (iv) the endocrine era (1900-1990) elucidating hormonal regulation; and (v) the molecular age (1990 to present) introducing genetic, epigenetic, and systems biology approaches. Key milestones include the discovery of spermatozoa, the development of semen analysis, the identification of the hypothalamic-pituitary-gonadal axis, assisted reproductive technologies, and contemporary omics-based diagnostics. Persistent challenges include an incomplete understanding of idiopathic infertility and limited treatment options for specific conditions.

Conclusions: Male fertility research demonstrates remarkable continuity alongside revolutionary breakthroughs. While ancient practitioners recognized lifestyle and environmental factors now validated by modern science, contemporary precision medicine approaches promise personalized diagnostics and targeted interventions. Future directions include integration of multi-omics data, artificial intelligence-assisted diagnosis, and regenerative medicine strategies for previously untreatable conditions.

This is the fourth and last episode of a series of four discussions on the differences between males and females in apparently non-andrological fields. You will read the transcript of discussions that actually took place at the Endocrinology Unit in Modena, Italy, in the form of the aporetic dialogues of ancient Greece. In this episode, the role of testosterone in gender differences in approaches to love will be explored. The discussants were divided into two groups: Group 1, which supports the thesis of a predominant role of testosterone, and Group 2, which opposes it. The first group argued that endogenous testosterone could shape approaches to love, regardless of psychological predispositions or sociocultural context. The second group highlighted the multifactorial nature of love, pointing to other hormonal and non-hormonal influences, such as neurotransmitters, cortisol, and sociological and psychological factors. In the end, an expert professor of endocrinology, acting as a referee, sought to resolve the aporia: Are the two theories equivalent, or is one superior?

Background: Extracellular vesicles (EVs) produced by accessory sex glands play a key role in sperm functionality, influencing motility, viability, acrosome integrity, metabolic activity, and capacitation. Most studies on the effects of EVs on spermatozoa have focused on ejaculated spermatozoa, which have already been exposed to their own native EVs. This prior exposure may contribute to the variability in reported effects of EVs on sperm function.

Objectives: To evaluate the role of EVs on the function of pig epididymal spermatozoa and their potential use for improving sperm preservation and in vitro fertilization (IVF).

Materials and methods: EVs were isolated from ejaculates of boars with proven fertility using ExoQuick ULTRA and subsequently characterized according to the guidelines of the International Society for Extracellular Vesicles (ISEV). Epididymal spermatozoa were collected from the cauda epididymis and diluted in MR-A medium before being incubated with EVs for 72 h. Sperm motility, viability, acrosome integrity, and mitochondrial activity were assessed at 0, 24, 48, and 72 h. These parameters were also evaluated at 24 and 48 h after sperm incubation at 38.5°C for 5 h. To evaluate the role of EVs on sperm function, PKA activity (pPKA) and tyrosine phosphorylation (Tyr-P) were assessed in capacitated spermatozoa by Western blot. IVF assays were also performed at 0 and 48 h of storage to evaluate sperm quality. The IVF parameters evaluated were oocyte penetration rate, sperm count per oocyte, and sperm adhesion to the zona pellucida.

Results: Incubation of spermatozoa with EVs improved motility, but impaired acrosome integrity and viability. Incubation of spermatozoa with EVs also caused a reduction in pPKA activity. Regarding Tyr-P, it was observed that EVs prevented the phosphorylation of 20 kDa proteins. IVF parameters decreased when fertilization was performed with EV-incubated spermatozoa.

Conclusions: Supplementation with EVs improves sperm motility, modulates capacitation by reducing protein phosphorylation, and reduces fertilization parameters.

Background: Sperm motility is essential for male fertility, and its regulation is dependent on the structural integrity of the axoneme. The axoneme consists of a conserved "9+2" microtubule arrangement and is supported by microtubule inner proteins. However, the functional significance of many microtubule inner proteins remains unclear. Cilia- and flagella-associated protein 77 (CFAP77) has been identified as a microtubule inner protein in various species, but its role in mammalian sperm function has not been fully elucidated.

Objectives: This study aims to investigate the function of CFAP77 in sperm motility and male fertility using a Cfap77 knockout mouse model.

Materials and methods: Cfap77 knockout mice were generated using the CRISPR-Cas9 system. Male fertility was assessed by mating tests, and sperm motility was analyzed using computer-assisted sperm analysis. Immunoblotting and immunoprecipitation-mass spectrometry were performed to determine CFAP77's localization and interaction with other microtubule inner proteins.

Results: We found that CFAP77 localized to the sperm flagella in mice. Moreover, Cfap77 knockout males exhibited significantly reduced fertility, with impaired sperm motility despite normal morphology. Immunoprecipitation-mass spectrometry analysis revealed that CFAP77 interacts with TEKTL1, and CFAP77 loss leads to a reduced amount of TEKTL1 in spermatozoa.

Discussion and conclusion: We demonstrate that CFAP77 is crucial for sperm motility and male fertility. The interaction between CFAP77 and other microtubule inner proteins suggests a role in stabilizing other microtubule inner proteins and regulating flagellar function. These results provide insights into the molecular mechanisms of sperm motility regulation.

Background: Cryopreservation is widely used in assisted reproductive technologies. While fresh sperm undergoes gradual time-dependent deterioration, it remains unclear whether thawed sperm exhibits a more accelerated decline.

Objectives: To directly compare the rate of deterioration in sperm motility, vitality, and DNA fragmentation between fresh washed and thawed sperm samples over time.

Materials and methods: This prospective study included semen samples from 50 males. Samples were split into two groups: Washed (freshly washed sperm) and Thawed (washed, cryopreserved for at least 2 weeks, and thawed). Sperm parameters, including motility, vitality, and DNA fragmentation index (DFI), were assessed immediately after processing (Time 1) and again after 75 min incubation at room temperature (Time 2). Additionally, control experiments tested whether cryoprotectant exposure alone could account for deterioration by comparing washed samples incubated with washing versus freezing medium (10 patient samples), and by assessing post-thaw washing (10 donor samples).

Results: Total sperm motility declined significantly more in thawed samples (29 ± 16%) compared to fresh washed samples (17 ± 9%, p < 0.0001). Vitality similarly deteriorated more in thawed samples (21 ± 14%) versus fresh washed samples (7 ± 5%, p < 0.0001). DNA fragmentation increased significantly only in thawed samples (p = 0.0331), reaching clinically critical levels (mean DFI 34 ± 13% at Time 2), compared to fresh samples which remained within normal range (12 ± 5%). Motility grade transitions differed markedly, with thawed samples showing direct transitions from Grade A motility to immotility, unlike fresh washed samples, which transitioned gradually from Grade A to Grade B. In additional control experiments, cryoprotectant exposure alone did not induce deterioration, and post-thaw washing did not improve metrics.

Discussion: Thawed sperm exhibited accelerated deterioration across all measured parameters, highlighting cumulative stress from cryopreservation. The rapid decline underscores the need to minimize the interval between thawing and insemination.

Conclusion: Thawed spermatozoa demonstrate significantly greater susceptibility to time-dependent deterioration compared to fresh washed samples, advocating for immediate use post-thaw to optimize reproductive outcomes.

Background: Peyronie's disease (PD) with severe penile curvature often requires surgical correction through plaque incision and grafting (PIG).

Objectives: To compare surgical outcomes between polyglycolic acid polymer grafts and porcine small intestinal submucosa (SIS) grafts in patients undergoing PIG for PD.

Materials and methods: This retrospective cohort study included patients with PD who underwent PIG using either Gore Bio-A (BioA group, n = 20) or SIS grafts (Cook Biotech, West Lafayette, IN, USA; SIS group, n = 21). The primary outcome was the incidence of postoperative erectile dysfunction (ED). Secondary outcomes included the degree of penile curvature correction, sensory disturbances, patient satisfaction, and surgical complications.

Results: The median age was 61 years in the BioA group and 57 years in the SIS group (p = 0.381). The BioA group exhibited a significantly higher rate of refractory ED compared to the SIS group (p = 0.006). No significant differences were observed between groups in terms of penile straightening, sensory alterations, postoperative complications, or the need for penile prosthesis implantation. Patient satisfaction was significantly higher in the SIS group (p = 0.015).

Discussion: This study is the first to directly compare Gore Bio-A and SIS grafts in PIG surgery for PD. Despite similar safety profiles and high curvature correction rates in both groups, erectile function outcomes were significantly better in the SIS group. Patient-reported satisfaction also favored SIS. Although associated with higher rates of ED, Gore Bio-A may still represent a viable option in selected cases, particularly when PIG is performed in conjunction with penile prosthesis implantation. Limitations include the retrospective, non-randomized design, and small sample size.

Conclusion: In this cohort, the SIS graft was associated with better postoperative outcomes than the BioA graft, with lower rates of refractory ED and higher patient satisfaction following PIG for PD.

Background: No study has yet explored telomere length or interaction in sperm nuclei of testicular cancer (TC) patients exposed to chemotherapy or radiotherapy. However, sperm telomere dynamics have emerged as a potential marker in male infertility.

Objectives: We aimed to investigate in a pilot and exploratory study whether TC and its adjuvant treatments alter sperm telomeres and DNA integrity during a 2-year follow-up after treatment.

Materials and methods: This ancillary study is part of the multicentric prospective and longitudinal French GAMATOX study. Twenty-nine TC patients treated with orchiectomy and either adjuvant chemotherapy (n = 14) or radiotherapy (n = 15) were included, alongside ten fertile donors. Semen samples were collected before orchiectomy and adjuvant therapy, and at 3, 6, 12, and 24 months after treatment. Sperm telomere length (STL) and telomere interactions were assessed by quantitative fluorescent in situ hybridisation (FISH). Sperm DNA fragmentation (SDF) was measured using the TUNEL assay, aneuploidy by FISH, and chromatin condensation defects by aniline blue staining.

Results: Before adjuvant therapy, patients presented a higher number of sperm telomere signals compared with controls (p = 0.004), persisting 2 years after treatment (p = 0.001). STL was not affected by tumour histology. Extremely short telomeres and the highest number of telomere signals per nucleus were more frequently observed after chemotherapy. SDF and chromatin condensation defects were transient and paralleled the recovery of conventional semen parameters, regardless of treatment type. A moderate increase in sperm aneuploidy was observed 6 months after chemotherapy (p = 0.03).

Conclusion: TC patients presented impaired sperm telomere interactions before and after adjuvant therapy, as reflected by a persistently elevated number of telomere signals per nucleus, and a higher prevalence of extremely short sperm telomeres, especially after chemotherapy. While relative STL remained comparable to controls, these findings raise questions about the impact of telomere architecture on germ cell tumour biology and post-treatment fertility.

Background: Microsurgical vasoepididymostomy (MVE) is the standard treatment for epididymal obstructive azoospermia (EOA). However, existing studies report inconsistent pregnancy and patency rates.

Objectives: To comprehensively review the therapeutic effects of various MVE techniques on EOA, address prior research controversies, and identify factors influencing MVE efficacy.

Materials and methods: Eligible studies focused on MVE outcomes, such as patency, pregnancy, or natural pregnancy rates. Relative pregnancy rate refers to natural pregnancies occurring in partners of patients with post-operative patency. Meta-analyses were performed using the "meta" R package. Heterogeneity was assessed with Q and I² tests.

Results: A total of 56 studies involving 3204 patients were included. End-to-end/end-to-side (EE/ES) techniques were associated with patency, pregnancy, and relative pregnancy rates of 65.0%, 23.0%, and 38.0%, respectively, whereas longitudinal intussusception vasoepididymostomy (LIVE) technique demonstrated slightly higher rates (68.0%, 27.0%, 40.0%). However these differences were not statistically significant (all p > 0.05). Compared with the 2-suture TIVE (72.0%) and LIVE (58.0%; p < 0.01) techniques, the 3-suture transverse intussusception vasoepididymostomy (TIVE) technique demonstrated significantly higher patency rates (89.0%). Pregnancy rates (33.0% vs. 26.0% vs. 28.0%) and relative pregnancy rates (38.0% vs. 33.0% vs. 42.0%) did not significantly differ among the three techniques (p > 0.05). Single-armed LIVE (SA-LIVE) demonstrated numerically higher patency (69.0% vs. 64.0%), pregnancy (31.0% vs. 26.0%), and relative pregnancy rates (46.0% vs. 39.0%) compared with double-armed LIVE (DA-LIVE). However, these differences were not statistically significant (all p > 0.05). Vessel-sparing SA-LIVE demonstrated superior patency (83.0%) compared with classical SA-LIVE (67.0%; p < 0.01), whereas pregnancy (38.0% vs. 31.0%) and relative pregnancy rates (both 47.0%) were not significantly different (p > 0.05). Bilateral MVE, genital infections, and the presence of motile spermatozoa were associated with increased patency rates. The overall late failure rate was 23.0%, with significantly higher rates for the EE/ES techniques (32.0%) than the IVE technique (15.0%; p = 0.03).

Conclusion: This meta-analysis confirms the efficacy of MVE for EOA. IVE has supplanted ES/EE, likely owing to its technical superiority and reduced rate of late failures, with LIVE emerging as the dominant approach. SA-LIVE and DA-LIVE yield comparable outcomes, and both should be recommended. Bilateral cases, infectious etiology, and motile epididymal spermatozoa predict increased patency rate. The relative pregnancy rate may better reflect effectiveness.

Background: More than 1000 genes have been identified as predominantly expressed in the human testis. Advances in gene editing technologies have enabled the rapid and efficient generation of genetically engineered mice. This approach facilitates the screening of genes essential for spermatogenesis by analyzing knockout mouse models.

Objectives: This study aimed to elucidate the essential genes in male reproductive function by generating knockout mouse models.

Materials and methods: We selected 11 target genes that may have potential roles in the male reproductive system based on a public database. Knockout mouse lines of these target genes were generated using the CRISPR/Cas9 system to elucidate their functions in male reproduction. Also, we conducted natural mating tests to elucidate fecundity and analyzed the phenotype of the knockout males.

Results: Natural mating tests revealed that all 11 gene-deficient mouse lines maintained normal male fertility. The phenotypic analysis, including testis appearance and weight, histology of testis and epididymis, and sperm motility and morphology, showed no apparent abnormalities.

Discussion and conclusion: These results suggest that each gene is not essential for male reproductive function.

Oxidative stress (OS) significantly contributes to male reproductive dysfunction, a factor implicated in a substantial fraction of infertility cases. This comprehensive review elucidates the intricate interplay between oxidative stress and male reproductive health, emphasizing the molecular and cellular mechanisms through which reactive oxygen species (ROS) impair sperm function. Key areas of focus include lipid peroxidation of sperm membranes, DNA damage, and apoptotic cell death, which collectively undermine sperm viability and fertility potential. The discussion extends to the impact of lifestyle and environmental factors on oxidative balance, highlighting how these elements intensify oxidative stress and subsequently exacerbate reproductive outcomes. Advances in therapeutic approaches are critically assessed, particularly the development and application of antioxidants in ameliorating oxidative damage and restoring reproductive functions. This review also explores innovative diagnostic techniques for detecting ROS and assessing oxidative damage within clinical settings, offering insights into future directions for research and clinical practice in managing male infertility related to oxidative stress.