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Bioorganic Chemistry Jun 2024In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to...
Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway.
In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1β, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.
PubMed: 38936048
DOI: 10.1016/j.bioorg.2024.107571 -
CVIR Endovascular Jun 2024Varicocele embolization is an effective, minimally invasive treatment option, with a symptom improvement rate of around 90%. However, anatomical variations and...
BACKGROUND
Varicocele embolization is an effective, minimally invasive treatment option, with a symptom improvement rate of around 90%. However, anatomical variations and post-embolization recurrences pose challenges to its efficacy. This article discusses the antegrade embolization technique as a viable alternative for cases in which retrograde embolization fails, offering a broader spectrum of treatment options for varicocele.
CASE PRESENTATION
This case report details the treatment of a 27-year-old male with a left varicocele, diagnosed during infertility assessment, using an alternative embolization technique. Despite initial failed attempts at retrograde catheterization via the femoral vein, a direct inguinal puncture of the left testicular vein was successfully performed under ultrasound guidance. A mixture of Glubran® and Lipiodol® was used for embolization, achieving varicocele embolization without complications. The patient was discharged 2 hours post-procedure, with follow-up confirming the procedure's effectiveness and safety.
CONCLUSION
This article introduces a less invasive, ultrasound-guided technique for varicocele embolization, presenting a viable alternative to surgery when conventional retrograde methods fail.
PubMed: 38935311
DOI: 10.1186/s42155-024-00446-6 -
Children (Basel, Switzerland) Jun 2024Accurate measurement of testicular volume (TV) in boys is an important tool in clinical practice, e.g., in varicocele treatment. This study aims to assess the degree of...
Accurate measurement of testicular volume (TV) in boys is an important tool in clinical practice, e.g., in varicocele treatment. This study aims to assess the degree of intra- and interobserver variability of testicular volume measurements. In a prospective study, boys between 11 and 17 years of age without testicular pathology were enrolled. Testicular ultrasound was performed by three investigators (A: pediatric radiologist; B: pediatric surgery/urology resident; C: pediatric urologist). Intraobserver variability was calculated in investigators B and C and interobserver variability between all three investigators. A total of 30 boys were enrolled. Mean intraobserver variability in both observers was +0.3% with a range of -39.6 to 51.5%. The proportion of measurements with a difference >20% was 18.6%. The mean interobserver variability was -1.0% (range: -74.1% to 62.8%). The overall proportion of measurements with a difference >20% was 35%. A lower testicular size of < 4 mL showed a significantly higher rate of >20% difference in both the intraobserver group (31.1% vs. 14.4%; = 0.035) and the interobserver group (63.2% vs. 26.2%; = 0.000031). Furthermore, the rate of >20% difference was significantly lower in obese compared to non-obese patients in both the intraobserver (2.8% vs. 22.4%; = 0.0084) and the interobserver group (24% vs. 40.8%, = 0.0427). Both intraobserver and interobserver variability in ultrasound-based TV measurements in pubertal boys contain a relevant degree of uncertainty that renders them unsuitable for individualized follow-up care. At the cohort level, however, mean differences in ultrasound-based TV measurements are low enough to make ultrasound comparisons reasonable.
PubMed: 38929320
DOI: 10.3390/children11060741 -
Fertility and Sterility Jun 2024To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA).
OBJECTIVE
To explore factors influencing microdissection testicular sperm extraction (micro-TESE) success in hypogonadal men with nonobstructive azoospermia (NOA).
DESIGN
Cohort study.
SETTING
University-affiliated male reproductive health center.
SUBJECTS
616 consecutive NOA patients with hypogonadism (total testosterone [T] levels <350 ng/dL) undergoing micro-TESE between 2014 and 2021. All patients had no prior sperm retrieval (SR) history.
EXPOSURE
Patients aged 23-55 underwent comprehensive clinical, laboratory, and histopathological diagnostic evaluation for NOA and were further categorized into two cohorts based on pre-SR hormonal stimulation.
MAIN OUTCOME MEASURES
Multivariable logistic regression analysis explored the associations between patient variables and micro-TESE success, defined as the presence of viable spermatozoa in extracted specimens. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were computed to assess the relationship between SR success and relevant predictors. SR rates were compared between patients receiving or not hormonal stimulation, and logistic regression analysis evaluated the effect of baseline FSH levels (i.e., normogonadotropic vs. hypergonadotropic classes) on SR success.
RESULTS
The overall micro-TESE success rate was 56.6%. Baseline FSH levels (aOR 0.97, 95% CI 0.94-0.99, p=0.04), pre-SR hormonal stimulation (aOR 2.54, 1.64-3.93, p=0.0002), presence of clinical varicocele (aOR 0.05, 0.01-0.51, p=0.04), history of previous varicocelectomy (aOR 2.55, 1.26-5.16, p=0.01), and testicular histopathology (p<0.01) were independent predictors of SR success. Among hormone-pretreated patients, pre-micro-TESE T levels and Delta T (absolute increase in T levels from baseline) were associated with SR success (p<0.05). A pre-micro-TESE T level of 418.5 ng/dL (AUC: 0.78) and a Delta T of 258 ng/dL (AUC: 0.76) distinguished patients with positive and negative SR outcomes. Subgroup analysis showed that pre-SR hormonal stimulation yielded a greater benefit for normogonadotropic patients than for those who were hypergonadotropic.
CONCLUSION
This study underscores the association between clinical factors and micro-TESE success in hypogonadal men with NOA. While causality is not established, our findings suggest that these patients may benefit from pre-SR interventions, particularly hormonal stimulation and varicocele repair.
PubMed: 38909671
DOI: 10.1016/j.fertnstert.2024.06.013 -
World Journal of Clinical Cases Jun 2024Varicocele embolization, a minimally invasive treatment for symptomatic varicoceles, carries a rare risk of complications like ureteral obstruction and hydronephrosis....
BACKGROUND
Varicocele embolization, a minimally invasive treatment for symptomatic varicoceles, carries a rare risk of complications like ureteral obstruction and hydronephrosis. This case report documents such a case to raise awareness of these potential complications and showcase minimally invasive surgical management as a successful solution.
CASE SUMMARY
A 35-year-old male presented with flank pain and hematuria following varicocele embolization. Imaging confirmed left ureteral obstruction and hydronephrosis. Laparoscopic ureterolysis successfully removed the embolization coil and repaired the ureter, resolving the patient's symptoms. Follow-up at six months and two years showed sustained improvement.
CONCLUSION
Minimally invasive surgery offers an effective treatment option for rare complications like ureteral obstruction arising from varicocele embolization.
PubMed: 38899306
DOI: 10.12998/wjcc.v12.i16.2856 -
Frontiers in Endocrinology 2024As an important gas signaling molecule, hydrogen sulfide (HS) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary,... (Review)
Review
As an important gas signaling molecule, hydrogen sulfide (HS) affects multiple organ systems, including the nervous, cardiovascular, digestive, and genitourinary, reproductive systems. In particular, HS not only regulates female reproductive function but also holds great promise in the treatment of male reproductive diseases and disorders, such as erectile dysfunction, prostate cancer, varicocele, and infertility. In this review, we summarize the relationship between HS and male reproductive organs, including the penis, testis, prostate, vas deferens, and epididymis. As lower urinary tract symptoms have a significant impact on penile erection disorders, we also address the potential ameliorative effects of HS in erectile dysfunction resulting from bladder disease. Additionally, we discuss the regulatory role of HS in cavernous smooth muscle relaxation, which involves the NO/cGMP pathway, the RhoA/Rho-kinase pathway, and K channel activation. Recently, various compounds that can alleviate erectile dysfunction have been reported to be at least partly dependent on HS. Therefore, understanding the role of HS in the male reproductive system may help develop novel strategies for the clinical treatment of male reproductive system diseases.
Topics: Hydrogen Sulfide; Humans; Male; Genitalia, Male; Animals; Erectile Dysfunction; Signal Transduction
PubMed: 38883604
DOI: 10.3389/fendo.2024.1377090 -
Asian Journal of Andrology Jun 2024Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce...
Varicocele repair in improving spermatozoa, follicle-stimulating hormone, and luteinizing hormone parameters in infertile males with azoospermia: a systematic review and meta-analysis.
Patients with azoospermia show a prevalence of varicocele of 10.9% and a 14.8% contribution to male infertility. Patients with azoospermia are thought to produce high-quality semen following varicocele treatment. Advising varicocelectomy prior to sperm retrieval in a reproductive program is still debated. This study reviewed the impact of varicocele repair on male infertility using several factors. A literature search was conducted using Scopus, PubMed, Embase, the Wiley Online Library, and Cochrane databases. Sperm concentration, sperm progression, overall sperm motility, sperm morphology, and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were also compared. Outcomes were compared between those who received treatment for varicocele and those who did not. The data from the pooled analysis were presented as standardized mean difference (SMD) along with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. Additionally, we conducted analyses for publication bias, sensitivity, and subgroup analysis as appropriate. Nine studies were included after screening relevant literature. Statistical analysis revealed a significant improvement in sperm concentration (SMD: 1.81, 95% CI: 0.84-2.77, P < 0.001), progressive sperm motility (SMD: 4.28, 95% CI: 2.34-6.22, P < 0.001), and sperm morphology (SMD: 3.59, 95% CI: 2.27-4.92, P < 0.001). Total sperm motility showed no significant difference following varicocele repair (SMD: 0.81, 95% CI: -0.61-2.22, P = 0.26). No significant differences were seen in serum FSH (SMD: 0.01, 95% CI: -0.16-0.19, P = 0.87) and LH (SMD: 0.19, 95% CI: -0.01-0.40, P = 0.07) levels as well. This study supports varicocele repair in infertile men with clinical varicocele, as reflected by the improvement in sperm parameters after varicocelectomy compared with no treatment. There were no significant improvements in serum FSH and LH levels.
PubMed: 38877692
DOI: 10.4103/aja202426 -
Journal of Pediatric Urology May 2024It is known the prevalence of varicoceles in adolescent men is 14-29% but there is debate surrounding implications on fertility. As obtaining a semen analysis (SA) may...
INTRODUCTION
It is known the prevalence of varicoceles in adolescent men is 14-29% but there is debate surrounding implications on fertility. As obtaining a semen analysis (SA) may be challenging, there is need for objective tests as measures of fecundity. Our aim was to investigate the relationship between testicular volume differential (TVD), varicocele grade, and total testicular volume (TTV) on seminal parameters including total motile sperm count (TMSC).
MATERIALS AND METHODS
We conducted a retrospective single-center chart review over 14 years of 486 Tanner V adolescent males. Three hundred and four met inclusion of palpable, non-operated left-sided varicocele who underwent at least one SA and ultrasound. Abnormal TMSC was defined by World Health Organization 2010 criteria for minimal reference ranges. Multivariate logistic regression, receiver operating characteristic analysis with Youden J-statistic and descriptive statistics were performed.
RESULTS
Three hundred and four Tanner V adolescents with median age of 18.0 years (18.0-19.0), median TTV of 34.5 cc (28.9, 40.2) and median TMSC of 62.5 million/ejaculate (25.4, 123.4) were evaluated. TTV cutoff of 29.5 cc was found to predict TMSC of <9 million/ejaculate with negative predictive value of 96.2% and odds ratio of 6.08 ([2.13-17.42], p < 0.001). TVD greater than 20% did not reach statistical significance with an odds ratio of 1.66 ([0.41-6.62], p = 0.50).
DISCUSSION
In clinical practice, each patient will need to have an individualized plan. Based on our data, for older adolescents (17 or 18 years) with varicocele and an abnormal TTV, clinicians may have a lower threshold for advising SA, and if unable to obtain, surgical intervention and/or closer surveillance should be stressed. Patients should be informed of their six-fold increase in abnormal SA. Patients with normal TTV should be advised they are at lower risk of having abnormal SA. Younger patients with varicocele and an initial TVD>20%, should be followed closely but intervention delayed until 17 or 18 to better assess TTV. The importance of trending patient data should be emphasized as a single measurement has low predictive value for developing adolescents. Limitations of our study include a retrospective design and the lack of uniform correlation between adolescent SA and paternity.
CONCLUSIONS
Total testicular volume less than 29.5 cc increased odds of abnormal semen analysis by over six times and had a negative predictive value of 96.2%. Ultrasound results may be useful for risk stratification and counselling on appropriateness of surgical intervention.
PubMed: 38876892
DOI: 10.1016/j.jpurol.2024.05.012 -
Tissue & Cell May 2024Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan...
Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·HO, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced HO levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.
PubMed: 38865824
DOI: 10.1016/j.tice.2024.102414 -
Human Genomics Jun 2024The prevalence of infertility among couples is estimated to range from 8 to 12%. A paradigm shift has occurred in understanding of infertility, challenging the notion... (Review)
Review
BACKGROUND
The prevalence of infertility among couples is estimated to range from 8 to 12%. A paradigm shift has occurred in understanding of infertility, challenging the notion that it predominantly affects women. It is now acknowledged that a significant proportion, if not the majority, of infertility cases can be attributed to male-related factors. Various elements contribute to male reproductive impairments, including aberrant sperm production caused by pituitary malfunction, testicular malignancies, aplastic germ cells, varicocele, and environmental factors.
MAIN BODY
The epigenetic profile of mammalian sperm is distinctive and specialized. Various epigenetic factors regulate genes across different levels in sperm, thereby affecting its function. Changes in sperm epigenetics, potentially influenced by factors such as environmental exposures, could contribute to the development of male infertility.
CONCLUSION
In conclusion, this review investigates the latest studies pertaining to the mechanisms of epigenetic changes that occur in sperm cells and their association with male reproductive issues.
Topics: Humans; Male; Epigenesis, Genetic; Infertility, Male; Spermatozoa; DNA Methylation; Animals
PubMed: 38835100
DOI: 10.1186/s40246-024-00626-4