Andrology最新文献

Spermatogenesis is a complex differentiation process that is facilitated by a series of cellular and molecular events. High-throughput genomics approaches, such as single-cell RNA sequencing, have begun to enable the systematic characterization of these events. However, the loss of tissue context because of tissue disassociations in the single-cell isolation protocols limits our ability to understand the regulation of spermatogenesis and how defects in spermatogenesis lead to infertility. The recent advancement of spatial transcriptomics technologies enables the studying of the molecular signatures of various cell types and their interactions in the native tissue context. In this review, we discuss how spatial transcriptomics has been leveraged to identify spatially variable genes, characterize cellular neighborhood, delineate cell‒cell communications, and detect molecular changes under pathological conditions in the mammalian testis. We believe that spatial transcriptomics, along with other emerging spatially resolved omics assays, can be utilized to further our understanding of the underlying causes of male infertility, and to facilitate the development of new treatment approaches.

Background: Chronic inflammation is a pervasive feature of aging and may be associated with testosterone in middle-aged and older men. Systemic immune-inflammation index (SII) is a novel inflammatory biomarker. We aimed to assess the association between SII and serum testosterone and free testosterone (FT) in middle-aged and older men.

Methods: Our study included males ≥ 40 years old in the 2011-2016 and 2021-2023 National Health and Nutrition Examination Survey. Multivariable regression analysis was used to explore the associations between SII and serum testosterone and FT in middle-aged and older men. Subgroup analysis was performed according to age.

Results: About 5354 participants were included, of which 2450 contained FT data. Multivariable linear regression found that SII exhibited an inverse association with serum testosterone (β -0.05, 95% CI -0.07 to -0.03, P < 0.001) and FT (β -0.03, 95% CI -0.05 to -0.01, P = 0.032) in middle-aged and elderly men. After SII was grouped as quartiles, serum testosterone was significantly lower in SII quartile 4 than in SII quartile 1 (β -0.05, 95% CI -0.08 to -0.02, P < 0.001). However, FT was not significantly lower in SII quartile 4 than in SII quartile 1 (β -0.03, 95% CI -0.07 to 0.01, P = 0.135). In subgroup analysis, the serum testosterone results were consistent with the overall results. However, only in the ≥60 years group, SII exhibited an inverse association with FT (β -0.06, 95% CI -0.1 to -0.02, P = 0.002) and was significantly lower in SII quartile 4 than in SII quartile 1 (β -0.06, 95% CI -0.12 to -0.01, P = 0.049).

Conclusions: Our study revealed an inverse association between SII and serum testosterone and FT in middle-aged and elderly men, particularly among men ≥ 60 years.

Background: Standardized methodology for reporting outcomes for male contraceptive trials has not been published. For male contraceptive studies that suppress spermatogenesis, contraceptive failures can occur during the sperm suppression phase or by sperm rebound or due to an unintended pregnancy during the efficacy phase. These three types of contraceptive failure differ from female contraceptives studies and necessitate a novel approach to reporting results from male contraceptive efficacy trials.

Methods: A standardized approach to reporting contraceptive outcomes for male contraceptive efficacy trials is proposed highlighting the three types of contraceptive failure: suppression failure, sperm rebound, and unintended pregnancy. This approach is used to retrospectively analyze published male contraceptive efficacy studies. Data on adverse events and other dropouts from these trials and data from condom use are also presented to give an overall picture of the contraceptive effectiveness of these methods.

Results: In 2217 men enrolled in the five male hormonal contraceptive efficacy studies included in the analysis, the suppression failure rate was 3.3% (95% CI: 2.6-4.2). The sperm rebound rate during efficacy was 1.4% (95% CI: 0.9%-1.9%), and the unintended pregnancy rate during efficacy was 1.1% (95% CI: 0.8%-1.7%). The combined contraceptive failure rate was 6.2% (95% CI: 5.2%-7.3%). In these trials, dropouts from adverse events occurred in 3.9% (95% CI: 3.1%-4.9%) of men, while discontinuations for other reasons occurred for 20% (95% CI: 18%-22%) of men. In total, 70% (95% CI: 68%-72%) of men experienced effective contraception.

Conclusions: Contraceptive failure in male contraceptive trials may be described with a three-outcome approach. Combining contraceptive failure measures with adverse event and dropout rates results in a clearer understanding of contraceptive effectiveness for the method under study.

Background: Classic Klinefelter syndrome (KS) is characterized by one extra X chromosome (47, XXY), leading to hypergonadotropic hypogonadism and higher risk of alterations in glycolipid homeostasis, cardiovascular diseases, and low bone mineral density. Most frequently, KS is diagnosed in adulthood because of infertility.

Objectives: To investigate the potential association between the age at first visit and the presence of comorbidities in patients with KS.

Materials and methods: In this cross-sectional retrospective study, we analyzed the data from 445 patients affected by non-mosaic 47, XXY KS and aged less than 50 years. Anthropometric measurements, biochemical and hormonal tests, semen analysis, scrotal echo-color Doppler, and dual energy X-ray absorptiometry (DXA) were performed on the patients. A subset of patients underwent testicular sperm extraction (TESE).

Results: Age at first visit significantly correlated positively with waist circumference (WC), body mass index (BMI), blood glucose, glycated hemoglobin, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and negatively with total testosterone (TT), calculated free testosterone (cFT), calcium, phosphorus, vitamin D, and lumbar Z-score. Age at the first visit >26 years was associated with higher frequency of increased WC, BMI, and hypercholesterolemia. Among the 199 patients who underwent testicular biopsy, the mean retrieval rate was 36.2% and was higher in the younger group (<26 years).

Discussion and conclusion: Early diagnosis and management of KS is important for preventing or reducing comorbidities later in life. In particular, glycemic, lipid, and phospho-calcium metabolism worsen with advancing age at first visit. Furthermore, early management of the patient seems to be associated with a higher probability of recovering spermatozoa through TESE.

Background: Real-world data on Peyronie's disease remains limited.

Objectives: Describe the demographics, clinical characteristics, and therapeutic management of Peyronie's disease patients in the United States.

Materials and methods: A retrospective analysis was conducted using the PearlDiver Mariner database (2010-2022). Male adults with Peyronie's disease were identified using the International Classification of Diseases codes. Data included demographics, clinical conditions, and treatments. Analysis was performed using R-based software.

Results: Among 176,969 patients (mean age 58.9 years), hypertension (72.9%), diabetes (40.4%), and obesity (31.1%) were the most common comorbidities. Smoking was prevalent in 41.5%. Dupuytren's contracture affected 3.1%, penile trauma 0.2%, erectile dysfunction 28.2%, and depression 19%. Most patients were from the southern US (42.9%). Social determinants of health were noted in 30.9%. Treatment was received by only 13.2%. Intraplaque injections were the most frequent therapy (7.2%) and showed an increasing trend (p = 0.014). Surgical interventions (8.1%) included plication (35.1%), grafting (13%), prosthesis implantation (36.2%), and multiple techniques (15.7%). Grafting was linked to higher de novo erectile dysfunction risk.

Discussion: Hypertension, diabetes, and smoking are frequent among Peyronie's disease patients. Erectile dysfunction and depression are common within a year of diagnosis. Despite multiple treatment options, only 15% of patients receive therapy. Injections are increasingly preferred, while surgery remains underutilized. Inflatable prostheses are the favored option for prosthetic management.

Conclusion: Peyronie's disease patients often have significant comorbidities. Treatment rates are low, with injections as the most used therapy. Surgical interventions are less common, with stable trends over time.

Castration has been a significant theme in mythology, religious traditions, and historical practices, often symbolizing transformation, sacrifice, and divine punishment. While the term is frequently associated with orchiectomy (removal of the testes), this study argues that penectomy (removal of the penis) must also be considered, particularly in myths where the symbolic weight of castration extends beyond mere fertility loss. The myth of Cybele and Attis serves as a compelling example, raising questions about the intended nature of Attis' self-mutilation and its implications.

Background: Testicular germ cell tumors (TGCT) are the predominant tumor in younger males. Usually, 5-year survival rates are quite high, but 15-20% of patients with metastatic non-seminomas are resistant to standard cisplatin-based therapy. Interfering with the epigenetic landscape has already been shown to be effective in prostate cancer. BRD9 is an epigenetic reader that is part of a chromatin-remodeling complex involved in regulation of gene expression.

Objectives: Alternative treatment options for therapy-resistant TGCT patients need to be investigated.

Materials and methods: BRD9 expression was analyzed by meta-analysis of microarray data as well as by Western blot and immunohistochemistry of tissue microarrays in TGCT cell lines and TGCT tissues. Viability was assessed by performing XTT-assay to determine the effect of BRD9 inhibition in TGCT cell lines. FACS analysis was used to display changes in cell cycle distribution as well as apoptosis. The impact on transcriptome level of BRD9 inhibition was analyzed by 3'mRNA-sequencing.

Results: BRD9 was heterogeneously expressed in TGCT cell lines and tissues. Nevertheless, inhibition of BRD9 led to a strong decrease in viability. I-BRD9 induced apoptosis as well as cell cycle arrest in G1-phase. On transcriptome level, prominent downregulation of pluripotency markers (NANOG, PRMD14, and KLF4) and upregulation of genes involved in epithelium development were detected.

Discussion: I-BRD9 treatment of TGCT cell lines reduced viability, induced apoptosis and cell cycle arrest while control cells remain only slightly affected. Transcriptomic data indicate exit of pluripotency and differentiation toward the epithelial fate. In fact, loss of pluripotency and differentiation seems to be a common aspect of germ cell tumors (GCT) reacting to drug application.

Conclusion: The data implicate I-BRD9 as a possible treatment alternative for TGCTs.

Background: Diabetes mellitus has increased significantly over the past decades. This disease affects the reproductive competence of diabetic men by disrupting spermatogenesis, fertility potential, penile erection, and ejaculation. However, hyperglycemic conditions' effects on the epididymis remain elusive despite its importance for sperm maturation.

Objective: We aimed to determine the effects of diabetes on the epididymis, using qualitative (systematic review) and quantitative (meta-analysis) approaches, to address the question: Can diabetes disrupt epididymal structure and function?

Materials and methods: We performed an extensive literature search identifying 66 eligible studies through PubMed, Web of Science, and Embase databases. Outcomes extracted from the studies included alterations in epididymal cell metabolism and morphology under hyperglycemic conditions. Pre-clinical studies published in murine were evaluated under a meta-analytical approach, whereas clinical investigations in humans were analyzed qualitatively (PROSPERO number is CRD42020208658).

Results: Type 1 diabetic patients presented post-ejaculatory epididymal hypotonia/atonia, whereas type 1 and 2 diabetic patients exhibited perturbation in the epididymal advanced glycation end-product axis. In murine, high glucose levels disturb the metabolism of epididymal cells, the androgenic profile, and the expression of hormone receptors within the organ. The low activity of antioxidant enzymes promoted an elevation of oxidative metabolite levels, creating a pro-oxidant microenvironment toxic to spermatozoa. All these deleterious mechanisms of diabetes trigger molecular and biochemical responses contributing to the deterioration of epididymis structure and function.

Discussion and conclusion: Our data indicated that diabetes may affect epididymis morphology and function through hormonal imbalance, glucose metabolism disturbance, and oxidative stress generation. These mechanisms may alter the luminal microenvironment and epithelial function, impairing organ functionality with consequences for sperm maturation. This review also highlighted several points that need investigation by further studies associating diabetes and epididymis to fill the knowledge gaps better.

Background: Sickle cell disease (SCD) is a prevalent hereditary disorder with significant morbidity, including potential impacts on male fertility. This study aims to evaluate the semen parameters in men with SCD and assess the outcomes of fertility preservation strategies.

Methods: This retrospective study included 121 men with SCD referred to the fertility Centre at Tenon University Hospital, Paris, between 2012 and 2023. Patients were categorized into three groups based on hydroxyurea (HU) exposure: without HU (WHU), ongoing HU(OHU), and previous HU (PHU). Clinical and semen parameters data were collected and compared with those of 107 healthy sperm donors. Semen parameters were analyzed according to World Health Organization guidelines, and sperm freezing protocols were standardized. Statistical analysis was performed to compare semen parameters between groups.

Results: Of the 121 patients, 117 successfully collected semen. All semen parameters, including volume, concentration, total count, motility, vitality, and morphology, were significantly reduced in SCD patients without HU exposure compared to donors. Nine had azoospermia and 45 had oligozoospermia, compared to 11 sperm donors with oligozoospermia (p < 0.05). The impact of HU on semen parameters could not be demonstrated due to the small-sample size. Fertility preservation outcomes showed a mean of 1.96 collections per patient, yielding a mean of 8.7 straws, with a majority requiring in vitro fertilization with intracytoplasmic sperm injection (ICSI) for future use. Seven patients used their cryopreserved sperm, resulting in two successful births.

Conclusions: This study, the largest of its kind, confirms significant alterations in semen parameters in men with SCD. Due to deleterious effects of treatments on male reproductive functions, fertility preservation remains crucial for these patients. Further research is needed to refine fertility preservation strategies and address the long-term reproductive health of men with SCD.

Background and objectives: The current retrospective study aimed to investigate the frequency and types of chromosomal abnormalities among a group of infertile men, as well as their impact on semen parameters, sperm retrieval rates (SRR), and intracytoplasmic sperm injection (ICSI) outcomes.

Materials and methods: Two thousand five hundred sixty-one Egyptian men were retrospectively evaluated between 2015 and 2020. Patients underwent infertility assessment, including semen analysis, hormonal evaluation, karyotyping, and, when applicable, Y chromosome microdeletion analysis. ICSI was conductedon a total of 1541 individuals.

Results: Our cohort included 1188 men with azoospermia (46.4%), and 457 having sperm concentrations less than 2 million/mL (17.8%). A normal male karyotype (46, XY) was observed in 2227 men (87%). We detected Klinefelter syndrome (KF) in 224 men (8.7%). Other chromosomal abnormalities, excluding KF, were identified in 110 men (4.3%), classified as compatible (N = 89) or incompatible (N = 21) with ICSI. The SRR for men with normal karyotypes was 48.6% (336/692), compared to 26.0% (19/73) for men with KF (P = 0.0003). Men with anomalies other than KF had a higher SRR of 55.6% (15/27) than those with KF (P = 0.0086). Clinical pregnancy rates were 44.1% for normal karyotypes, 33.3% for KF, and 32.3% for compatible chromosomal abnormalities (p > 0.05).The blastulation rate for men with compatible chromosomal abnormalities was 11.9%, while it was 27% for KF (p = 0.0001). Fertilization (FR) and implantation rates (IR) for KF were comparable to those with compatible abnormalities (FR: 65 .6% vs. 70.7%; IR: 18 .8% vs. 19.3%, P = 0.477, P = 0.530). The total testosterone (TT) level did not discriminate or predict testicular sperm extraction (TESE) outcome in men with KF and in men with other anomalies.

Discussion & conclusion: The incidence of chromosomal abnormalities as a cause of severe male infertility in this study is within the similar range reported internationally and in the Mediterranean region. The impairment of spermatogenesis is reflected by the lower SRR in KF patients. Spermatozoa retrieved from men with KF are expected to yield the same FR, blastulation rate (BR), and IR as those collected from men with a normal set of chromosomes. However, the negative prognostic effects of other chromosomal abnormalities on ICSI outcomes, especially low BR, should be clearly explained to these patients during counseling for assisted reproductive techniques.