Spermatogenesis In Infertile Men Research Articles

The role of testicular stiffness derived from shear wave elastography in the assessment of spermatogenesis in men with varicocele.

Varicocele is a major correctable cause of male infertility. Shear wave elastography (SWE) represents a valuable approach for assessing spermatogenesis in infertile men; however, its application in infertile men with varicocele remains unreported in the literature to date. The objective of this study was to investigate the correlation between testicular stiffness and spermatogenesis in individuals with varicocele. A total of 568 participants with left-side varicocele and 475 age-matched healthy controls were enrolled. The mean, left, and right testicular volumes (Volume-mean, Volume-L, and Volume-R), the mean elastic modulus of bilateral, left, and right testes (Emean, Emean-L, and Emean-R); the maximum elastic modulus of bilateral, left, and right testes (Emax, Emax-L, and Emax-R); the minimum elastic modulus of bilateral, left, and right testes (Emin, Emin-L, and Emin-R) were calculated. Receiver operating characteristic (ROC) curves for Volume-R and Emax were constructed to identify participants with sperm concentrations below 5 million/mL. The areas under the ROC curves (AUCs) were 0.801 and 0.775, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.820 and sensitivity and specificity of 94.6% and 59.8% [95% confidence interval (CI): 0.772-0.867, P<0.01], respectively. A total of 69 participants underwent microsurgical varicocelectomy (including 42 cases with improved semen results and 27 without). The ROC curves of Emax-L and Volume-L were constructed for the differential diagnosis between the improved and unimproved groups; the AUCs were 0.723 and 0.855, respectively. Combining these 2 markers improved their diagnostic value with an AUC of 0.867 (95% CI: 0.772-0.961, P<0.01) and sensitivity and specificity of 81.5% and 81.0%, respectively. Our findings suggest that SWE can be used for varicocele to assess testicular parenchyma damage and Volume-L combined with Emax-L offers a more accurate method for predicting semen parameter improvement after microscopic subinguinal varicocelectomy in men with varicocele.

Long-acting recombinant human follicle-stimulating hormone (SAFA-FSH) enhances spermatogenesis.

Administration of follicle-stimulating hormone (FSH) has been recommended to stimulate spermatogenesis in infertile men with hypogonadotropic hypogonadism, whose sperm counts do not respond to human chorionic gonadotropin alone. However, FSH has a short serum half-life requiring frequent administration to maintain its therapeutic efficacy. To improve its pharmacokinetic properties, we developed a unique albumin-binder technology, termed "anti-serum albumin Fab-associated" (SAFA) technology. We tested the feasibility of applying SAFA technology to create long-acting FSH as a therapeutic candidate for patients with hypogonadotropic hypogonadism. SAFA-FSH was produced using a Chinese hamster ovary expression system. To confirm the biological function, the production of cyclic AMP and phosphorylation of ERK and CREB were measured in TM4-FSHR cells. The effect of gonadotropin-releasing hormone agonists on spermatogenesis in a hypogonadal rat model was investigated. In in vitro experiments, SAFA-FSH treatment increased the production of cyclic AMP and increased the phosphorylation of ERK and CREB in a dose-dependent manner. In animal experiments, sperm production was not restored by human chorionic gonadotropin treatment alone, but was restored after additional recombinant FSH treatment thrice per week or once every 5 days. Sperm production was restored even after additional SAFA-FSH treatment at intervals of once every 5 or 10 days. Long-acting FSH with bioactivity was successfully created using SAFA technology. These data support further development of SAFA-FSH in a clinical setting, potentially representing an important advancement in the treatment of patients with hypogonadotropic hypogonadism.

Effect of a single-dose denosumab on semen quality in infertile men (the FITMI study): study protocol for a randomized controlled trial

BackgroundInfertility is a common problem globally and impaired semen quality is responsible for up to 40% of all cases. Almost all infertile couples are treated with either insemination or assisted reproductive techniques (ARTs) independent of the etiology of infertility because no medical treatment exists. Denosumab is an antibody that blocks RANKL signaling and inhibition of testicular RANKL signaling has been suggested to improve semen quality in a pilot study. This RCT aims to assess whether treatment with denosumab can improve spermatogenesis in infertile men selected by serum AMH as a positive predictive biomarker. This paper describes the design of the study.Methods/designFITMI is a sponsor-investigator-initiated, double-blinded, placebo-controlled 1:1, single-center, randomized clinical trial. Subjects will be randomized to receive either a single-dose denosumab 60 mg subcutaneous injection or placebo. The study will be carried out at the Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen. The primary outcome of the study is defined as the difference in sperm concentration (millions pr. mL) one spermatogenesis (80 days) after inclusion.DiscussionWe describe a protocol for a planned RCT aimed at evaluating whether treatment with denosumab can improve the semen quality in infertile men selected by using serum AMH as a positive predictive biomarker. The results will provide evidence crucial for future treatment in a patient group where there is a huge unmet need.Trial registrationClinical Trials.gov NCT05212337. Registered on 14 January 2022.EudraCT 2021–003,451-42. Registered on 23 June 2021.Ethical committee H-21040145. Registered on 23 December 2021.

Применение комплекса природных противомикробных пептидов и цитокинов при мужском бесплодии и хроническим простатите

Chronic prostatitis (CP) has long been considered one of the common causes of male infertility. The influence of therapy for CP on spermatogenesis is well studied. However, recently, especially in the era of the new coronavirus infection (COVID-19), much attention has been paid to the effects of cytokines on the pathogenesis of the inflammatory process, and their impact on male fertility.To study the effect of a complex of natural antimicrobial peptides and cytokines (Superlymph) on ejaculate, MAR test, oxidative stress (OS), and sperm DNA fragmentation (SDF) in men with infertility and a history of CP. In some patients, the level of cytokines before and after treatment was determined.A total of 583 infertile men with a history of CP, aged 18-75 years, were screened according to the inclusion/ exclusion criteria. In group I, patients received antioxidant stimulation of spermatogenesis (triovit, trental, mexidol) in combination with a complex of natural antimicrobial peptides and cytokines (Superlymph) one suppository 25 IU at night for 20 days for 1-3 weeks and for 6-8 weeks for 2 months. In group II, antioxidant stimulation of spermatogenesis was prescribed along with suppositories for the prevention of CP for 2 months. The evaluated criteria included sperm analysis, MAR test, oxidative stress in spermatozoa (reactive oxygen species (ROS)) and SDF. The levels of seminal plasma cytokines were also measured before and after treatment in 32 patients using the Bio-Plex Pro panel for the simultaneous determination of 17 human cytokines, the Human Cytokine 17-plex Assay. Statistica-10 software was used for statistical analysis (p<0.05).Of 135 eligible patients, results were collected from 125 men (mean age 31.7 +/- 13.4 years). In group I, there was a more pronounced increase in motility by 42.3%, a decrease in the MAR-test level by 64.7%, oxidative stress in spermatozoa by 56.1%, and SDF by 25.6%, compared to group II (30.4 %, 10.5%, 45.7%, 21.9%), respectively. All these changes were significant with the exception of a decrease in the level of SDF. In group I, there was a predominant increase in the activity of anti-inflammatory cytokines (IL-4, 10, 13), a decrease in the level of pro-inflammatory cytokines ((IL-2, 12). In group II, there was a significant decrease in both pro-inflammatory (IL-2, 6, 8), and anti-inflammatory cytokines (IL-4). The remaining changes were insignificant. Among mild side effects, there were a change in the color of the sclera in 4 (3.2%), anal pain in 3 (2.4%), a decrease in libido in 2 (1.6%) patients. No differences between groups in the frequency of side effects were recorded (p>0.05).Antioxidant stimulation of spermatogenesis in infertile men and CP is an effective and safe. The addition of a complex of natural antimicrobial peptides and cytokines (Superlymph) leads to a more profound increase in sperm motility, a decrease in the MAR-test, oxidative stress in sperm cells, which potentiates the effects of therapy. The use of Superlymph is accompanied by a more pronounced positive effect on pathospermia, an increase in anti-inflammatory and a decrease in pro-inflammatory cytokines. In the contrary, in control group, where patients received antioxidant stimulation of spermatogenesis, only a decrease in the level of main cytokines was observed. The effect of a complex of natural antimicrobial peptides and cytokines (Superlymph) on the level of SDF, as well as the relationship with fertility and childbirth rates, requires further study.

The Roles of Aromatase Inhibitors in Treating Hypogonadism and Male Infertility

Testis is an organ with both endocrine and exocrine functions. The former stands for testosterone release, and the latter represents sperm production. Spermatogenesis is a process highly depending on adequate supply of testosterone by the Leydig cells of the testis. In men at the reproductive age, more than 90% of testosterone produced is used for spermatogenesis. In men with diminished testosterone secretion in testis, or hypogonadism, the spermatogenesis process is impaired. Testosterone can be converted into estradiol through the catalyzation of aromatase, a cytochrome P450 enzyme presented in the peripheral tissue. Blocking the activity of aromatase causes an elevation of serum testosterone and a decrease of serum estradiol levels. These effects result in an increase of testosterone-to-estradiol ratio. Infertile males with dysfunction of spermatogenesis may demonstrate a low testosterone-to-estradiol ratio. Studies have shown that aromatase inhibitors (AIs) are beneficial to treat patients with impaired spermatogenesis, by demonstrating improvement of the semen parameters in men with oligoasthenoteratozoospermia. Besides, AIs can also be applied in other health issues, such as hypogonadism-related erectile dysfunction, short statue, depression, or male breast cancer. There are two different types of AIs: steroidal and nonsteroidal. Steroidal AI (e.g., testolactone) is an irreversible, but weaker inhibitors, while nonsteroidal AIs (e.g., letrozole and anastozole) are potent reversible inhibitors. Both types of AIs demonstrate plausible effects to improve semen parameters. In this review, the physiological action of aromatase and the indications of AIs treatment are discussed in detail, especially focusing on the function of spermatogenesis in infertile men.

The role of nitric oxide on spermatogenesis in infertile men with azoospermia

Objectives: The underlying pathophysiological mechanisms of azoospermia is still unclear. The aim of the study was to evaluate nitric oxide synthase (NOS) isoforms and free radical release in testicular sperm extraction (TESE) in infertile men with azoospermia. Materials and methods: The study included 40 men (mean age: 37.2±2 years; range 25 to 55 years) with azoospermia which were divided into two groups: spermatozoa-present (n=20) and spermatozoa-absent (n=20). Testicular samples were examined morphologically, immunohistochemically, and biochemically. The TESE samples were examined according to number of mast cells stained with toluidine blue; immunohistochemically with three types of NOS isoforms, and free radicals were measured with chemiluminescence method, respectively. Results: Endothelial NOS (eNOS) reaction in spermatozoa-present group was considerably higher than spermatozoa-absent group (p&lt;0.001). Compared to the spermatozoa-present group, inducible NOS (iNOS) reaction was higher than the spermatozoa-absent group (p&lt;0.05). Neuronal NOS (nNOS) reaction was only prominent in Leydig cells in both groups. Mast cells increased (p&lt;0.05) in the interstitial area surrounding seminiferous tubules in spermatozoa-absent samples. Superoxide radical generation in spermatozoa-present samples was significantly lower (p=0.0003). The peroxynitrite ratio in spermatozoa-absent samples was significantly higher (p=0.0038). Conclusion: These results suggest that eNOS, iNOS, and mast cells play an important role in spermatogenesis process in azoospermic men.

A preliminary study of the biochemical environment of infertile testes with clinical varicocele

PurposeTo investigate the role of proton magnetic resonance spectroscopy.(1H-MRS) in the assessment of the biochemical environment of testes in infertile men with clinical varicocele. MethodsIn this prospective IRB approved study, 13 infertile men with clinical varicocele and 11 age-matched controls were assessed. 1H-MRS was performed using a single voxel point-resolved spectroscopy (PRESS) sequence with TR/TE: 2000/25 ms. Normalized metabolite concentrations, defined as ratios of the calculated metabolite concentrations relative to total creatine (tCr) concentration were compared between infertile testes with clinical varicocele and normal testes using nonparametric statistical tests. Logistic regression analysis was performed to assess the most significant predictor for the diagnosis of varicocele. ResultsSeveral metabolic peaks were found in both infertile testes with clinical varicocele and normal testes. Most prominent peaks were the following: total choline (tCho), tCr, myo-inositol (mI), Glx, and total lipids and macromolecules resonating at 0.9 ppm (TLM09), 1.3 ppm (TLM13) and 2.0 ppm (TLM20). Lower normalized concentrations of tCho (P = 0.001), mI (P = 0.012), Glx (P = 0.011), TLM09 (P = 0.027), TLM13 (P = 0.035) and TLM20 (P = 0.021) were found in infertile testes with clinical varicocele compared with normal men. Total Cho proved the most significant predictor for the diagnosis of clinical varicocele (P = 0.001). Conclusions1H-MR spectra of infertile testes with clinical varicocele showed decrease in normalized concentrations of tChol, ml, Glx and lipids. 1H-MRS of the testes might be used as a noninvasive marker of deranged spermatogenesis in infertile men with clinical varicocele.

Assessment of seminal granulysin in infertile men with varicocele.

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele-associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case-controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n=20), infertile men without varicocele (n=30) and infertile men with varicocele (n=40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.

MP70-18 SEMINAL LEVEL OF CLUSTERIN IN INFERTILE MEN AS A SIGNIFICANT BIOMARKER REFLECTING SPERMATOGENESIS

You have accessJournal of UrologyInfertility: Basic Research & Pathophysiology1 Apr 2016MP70-18 SEMINAL LEVEL OF CLUSTERIN IN INFERTILE MEN AS A SIGNIFICANT BIOMARKER REFLECTING SPERMATOGENESIS Teruo Fukuda, Hideaki Miyake, Noritoshi Enatsu, Kei Matsushita, and Masato Fujisawa Teruo FukudaTeruo Fukuda More articles by this author , Hideaki MiyakeHideaki Miyake More articles by this author , Noritoshi EnatsuNoritoshi Enatsu More articles by this author , Kei MatsushitaKei Matsushita More articles by this author , and Masato FujisawaMasato Fujisawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1443AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The objective of this study was to assess the impact of seminal clusterin level on spermatogenesis in infertile men. METHODS This study included 89 men who had visited our clinic due to infertility, consisting of 28, 33, and 28 diagnosed with normospermia, oligozoospermia and non-obstructive azoospermia (NOA), respectively. The seminal clusterin concentrations in these 89 men were measured by sandwich enzyme-linked immunosorbent assay. RESULTS The seminal clusterin level in men with NOA was significantly decreased compared with that of those with oligozoospermia or normospermia. Microdissection testicular sperm extraction (MD-TESE) was performed in the 28 NOA men, and sperm was successfully retrieved from 9. The expression level of clusterin protein in testes specimens from the 28 NOA men were evaluated by immunohistochemical staining, and a significant correlation was noted between testicular clusterin protein expression and seminal clusterin levels in these men. Furthermore, of the several parameters available prior to MD-TESE, the univariate analysis identified serum follicle stimulating hormone (FSH) level and seminal clusterin level as significant predictors of sperm retrieval, and of these only serum FSH level was shown to be independently associated with sperm retrieval in the multivariate analysis. CONCLUSIONS These findings suggest that the seminal clusterin level could be used as a biomarker reflecting the status of spermatogenesis in infertile men. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e913-e914 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Teruo Fukuda More articles by this author Hideaki Miyake More articles by this author Noritoshi Enatsu More articles by this author Kei Matsushita More articles by this author Masato Fujisawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Seminal level of clusterin in infertile men as a significant biomarker reflecting spermatogenesis.

The objective of this study was to assess the impact of seminal clusterin level on spermatogenesis in infertile men. This study included 89 men who visited our clinic due to infertility, consisting of 28, 33, and 28 diagnosed with normospermia, oligozoospermia and nonobstructive azoospermia (NOA) respectively. The seminal clusterin concentrations measured by enzyme-linked immunosorbent assay were 47.9, 28.2 and 18.4ngml-1 in men with normospermia, oligozoospermia and NOA, respectively, with significant differences among these three groups (P<0.01). Microdissection testicular sperm extraction (MD-TESE) was performed in the 28 men with NOA, and spermatozoon was successfully retrieved from 9. There was a significant correlation between seminal clusterin level and testicular clusterin protein expression evaluated by immunohistochemical staining in these men with NOA (P=0.026). Of several parameters available before MD-TESE, the univariate analysis identified serum follicle-stimulating hormone (FSH) level <10IUml-1 and seminal clusterin level ≥18ngml-1 as significant predictors of sperm retrieval, and of these, only serum FSH level <10IUml-1 was shown to be independently associated with sperm retrieval in the multivariate analysis. Accordingly, it might be worthy to further evaluate the significance of seminal clusterin level as a biomarker for the assessment of spermatogenic status in infertile men.

Aromatase inhibitors in the treatment of oligozoospermic or azoospermic men: a systematic review of randomized controlled trials.

The aim of this study as to analyze published evidence regarding the effectiveness of aromatase inhibitor therapy on improving spermatogenesis in infertile men. We carried out a systematic review of randomized controlled trials. The date of the most recent search was October 4, 2015. Two authors independently selected relevant clinical trials, assessing their methodological quality and extracting data. Three studies were included in this review with a total of 100 participants; however, we were able to include data from only 54 participants in the analysis. In the representation of meta-analysis with a single study comparing testolactone versus placebo, related to the hormone concentrations, there was a statistically significance difference favoring the use of testolactone for Luteinizing Hormone (LH); Estrogen (E2); free Testosterone (free T); free Estrogen (free E2); 17-Hydroxyprogesterone (17OHP); prolactin (PRL). In another analysis from a single study comparing letrozole versus anastrozole, there was also a statistically significance difference favoring the use of letrozole for the increase in both the sperm count and LH. There is only low quality evidence regarding the effectiveness of aromatase inhibitor therapy in infertile men. Further trials are needed with standardized interventions and outcomes.

Seminal Anti-Mullerian Hormone in Fertile and Infertile Men = هورمون إنتي-موليرين المنوي في الرجال الخصيبين و العقيمين

Objective: Anti-Mullerian hormone (AMH) is a glycoprotein of the transforming growth factor β-superfamily, is produced by Sertoli cells and have been proposed as direct marker of their function and indirect marker of spermatogenesis. The aim of this study is to demonstrate that serum and seminal AMH as non-invasive marker of spermatogenesis in infertile men and to find the relationship between seminal AMH, FSH, LH, prolactin and testosterone. The aim of this study is to demonstrate that serum and seminal AMH as non-invasive marker of spermatogenesis in infertile men and to find the relationship between seminal AMH, FSH, LH, prolactin and testosterone. Setting: Al-Batool Teaching Hospital and Al-Duaa clinical lab. Design : prospective study. Participants and Methods: The study was conducted on seventy male subjects aged less than fifty years for the period from Sept2012-Feb2013. Infertile men were classified into azoospermics (n=20), oligospermics (n=20), and fertile men as controls (n=30). Serum concentrations of FSH, LH, prolactin and testosterone were measured using ELISA. Serum AMH and AMH in seminal plasma concentrations were measured using AMH/MIS enzyme immunoassay sorbant kit. Results: Infertile men had lower seminal and serum AMH levels and was statistically significant. There was a significant negative correlation between seminal AMH and FSH in azoospermic men while no significant correlation was found with LH, prolactin and testosterone. Concerning oligospermic men, a significant positive correlation was found between seminal AMH and testosterone while no significant correlation was found with FSH, LH and prolactin. Conclusion: the present study found that AMH in seminal plasma can be used as indirect marker of infertility in men.

Have androgen receptor gene CAG and GGC repeat polymorphisms an effect on sperm motility in infertile men?

Androgens and a normal androgen receptor (AR) are required for normal spermatogenesis. We investigated polyglutamine (CAG) and a polyglycine (GGC) tract in Italian men with defective spermatogenesis. We studied a group of 40 infertile men with spermatogenesis failure without Y-chromosome microdeletions compared with 60 normozoospermic ones. The distributions of both polymorphisms, within the normal range of Caucasian populations, were similar among infertile men and controls. Nonetheless, we observed that the frequency comparison of each CAG allele showed a statistical difference in the allele CAG 22; GGC 17 was the more predominant allele in infertile men than in controls. Moreover, to investigate the hypothesis that semen characteristics are perturbed by androgen receptor allele variants, we tried to detect a link between triplets and sperm motility in all subjects (cases plus controls). Subjects were subdivided into three groups, based on calculated allele frequencies. A significantly decreased motility, related to a longer CAG and GGC tracts, and marked differences between the groups exist for both polymorphisms. Our data highlight a probable relationship between the allele CAG 22/GGC 17 and a defective spermatogenesis in infertile men, suggesting that these polymorphisms might have an important effect on AR function.

Sensitivity and specificity of serum FSH and testis size in predicting the existence of spermatogenesis in azoospermic infertile men

The objective of research was to determine the sensitivity, specificity and positive predictive value of serum follicle stimulating hormone and testis size in predicting spermatogenesis in infertile men with azoospermia. In a prospective study, azoospermic men were studied. Serum follicle stimulating hormone measurement and scrotal sac ultrasonography were performed. Bilateral testis biopsy was performed for all of these patients. The sensitivity and specificity of follicle stimulating hormone and testis size were determined to predict the existence of different cellular steps of spermatogenesis. Of eighty infertile men who recruited into the study, 53 patients did not represent any different cellular steps of spermatogenesis, while 27 of them had various steps of such differentiation. Among the 53 patients without cellular steps of spermatogenesis in the biopsy, 41 were predicted to be azoospermic based on their serum follicle stimulating hormone levels (77.3% sensitivity), and of 27 patients with various cellular steps of spermatogenesis in the biopsy, 23 were predicted to have spermatozoa according to the follicle stimulating hormone level (85.2%) specificity. It is suggested that combination of these two indicators can substitute the invasive testis biopsy for predicting the existence of spermatozoa in infertile men with azoospermia.

Our environment and our gametes: what human ARTs can add to the discourse

Our environment and our gametes: what human ARTs can add to the discourse

UP-2.058: Recovery of Spermatogenesis After Microsurgical Subinguinal Varicocelectomy in Infertile Men

There are conflicting opinions on favorable influence of surgical treatment varicocele on recovery of spermatogenesis for patients with clinical varicocele and infertility (Evers and Collins, 2001, 2003; Ficcara et al., 2006; Richardson et al., 2007; Marmar et al., 2007). The objective: to evaluate the effect of microsurgical subinguinal varicocelectomy on recovery of spermatogenesis in infertile men.

Molecular aspects of male fertility

The 5th International Workshop on Molecular Andrology took place between 8 and 10 May 2009 at the Altes Schloss in Giessen, Germany, and was organized by A. Meinhardt, H.‐C. Schuppe and J. Klug. ![][1] See Glossary for abbreviations used in this article Two crucial challenges face modern andrology: to find a solution for male infertility and to develop an effective, reversible male contraceptive. Infertility is estimated to affect at least one in 20 men worldwide, and the majority of cases are of idiopathic—possibly genetic or epigenetic—aetiology. Technical advances in assisted reproduction, such as the intracytoplasmic injection of defective sperm or immature germ cells into a mature egg, have transformed the treatment of male infertility; however, new concerns have been raised about the propagation of genetic or epigenetic abnormalities that might otherwise be excluded by normal fertilization or conventional in vitro fertilization. In addition, andrology is at the epicentre of the stem cell revolution, as spermatogonial stem cells (SSCs) have become a crucial model system to explore stem cell potential. It is hoped that the understanding of the regulation of SSCs will allow the restoration of spermatogenesis in infertile men. The need to overcome these diverse challenges and seize emerging opportunities is driving andrologists to decipher the molecular pathways—which are often altered in disease—that govern the male reproductive system. Against this dynamically evolving background, many of the world's leading experts in andrology gathered at the Altes Schloss in Giessen for the 5th International Workshop on Molecular Andrology, which was also the first Symposium of the newly established Clinical Research Unit in Andrology at Marburg and Giessen. The castle, which is used as a museum and art gallery, was host to 90 excellent scientific presentations and the surrounding discussions, organized around three main topics. The first topic was the regulation of differentiation and … [1]: /embed/graphic-1.gif

Initial experience with high resolution testicular MRI to predict areas of spermatogenesis in infertile men with nonobstructive azoospermia (NOA): a novel tool for planning sperm retrieval

Initial experience with high resolution testicular MRI to predict areas of spermatogenesis in infertile men with nonobstructive azoospermia (NOA): a novel tool for planning sperm retrieval

Inhibin B reference data for fertile and infertile men in Northeast United States

OBJECTIVE: To determine normative levels of inhibin B and examine levels in relationship to FSH, sperm count, and motility in a cohort of fertile and infertile men from the Northeast United States. DESIGN: Prospective comparative study of inhibin B levels in fertile and infertile patient groups. MATERIALS AND METHODS: Fertile men were recruited among those presenting for elective vasectomy at a tertiary academic referral center. Men being evaluated for infertility were also recruited within the same practice. Exclusion criteria included current use of hormonal medication, prior vasectomy, and absence of one testicle, unilateral testicular atrophy or hypogonadism. Blood samples were drawn from each participant and inhibin B and FSH levels were measured by immunoassay. Semen parameters were obtained for the infertile group. Descriptive statistics for both fertile and infertile groups were calculated and simple and multiple linear regression analysis was performed to examine the relationship between semen parameters and inhibin B concentration in the infertile group. RESULTS: A total of 56 fertile and 85 infertile men were recruited. The mean serum inhibin B was higher in the fertile group (132 pg/mL) than the infertile group (78 pg/mL, p < 0.001). The 95% CI for inhibin B in fertile men was 114 - 155 pg/ml and 65 - 93 pg/ml for infertile men. The mean FSH levels were 3.5 and 5.6 IU/L for the fertile and infertile groups, respectively (p < 0.001). Inhibin B levels correlated positively (R square = 0.27, p < 0.001) and FSH correlated negatively (R square = 0.33, p < 0.001) with total sperm concentration. General linear model multiple regression demonstrated that the parameters were equally predictive of sperm concentration. This resulted from the high negative correlation between FSH and inhibin (R square = 0.46, p < 0.001). CONCLUSIONS: Inhibin B levels in fertile men were defined and found to be similar, but not identical, to those reported in other geographic regions. Both inhibin B and FSH are useful markers of spermatogenesis in infertile men.

Defective Spermatogenesis in Cryptorchid Testes: Cause or Effect?

Martin et al. (2008) recently published their quantitative meta-analysis focusing on the estrogen hypothesis of testicular dysgenesis syndrome. I congratulate the authors on their thorough review and excellent summary of the existing literature. The study findings are in line with other articles; however, there are several concerns that need further attention. Martin et al. (2008) pointed out that a common etiology underlies impaired spermatogenesis, male reproductive tract abnormalities such as hypospadias and cryptorchidism, and testicular cancer. I am especially interested in exploring the relationship between defective spermatogenesis and cryptorchidism. Maldescended testes is commonly cited as an important cause for defective spermatogenesis (Tomomasa et al. 2002). In contrast, testicular ascent (acquired cryptorchidism) could also be a risk factor for spermatogenesis in infertile men without any history of maldescended testes (Mieusset et al. 1997). However, it remains controversial whether impaired testicular function and spermatogenesis imparts an increased risk—and therefore represents a common pathogenetic mechanism of both congenital and acquired cryptorchidism—or is merely associated with disease. Recently, a potential link was proposed relating spermatogenesis and testicular descent (Skandhan and Rajahariprasad 2007). Observational studies of many lower animals (rodents, bats, and insectivores) have revealed that testicular position is dependent on its functional status: It is scrotal during breeding seasons and inguinal or abdominal at other times (Bannister and Dayson 1995). Therefore, it is possible that maldescended testes or acquired testicular ascent simply report a state of defective testicular function and spermatogenesis. In animal studies, estrogen has been shown to increase the number of type A spermatogonia, together with inhibition of their differentiation into further steps (Kula et al. 1997). Furthermore, supportive evidence suggests that undifferentiated type A spermatogonia are the only germ cells present in cryptorchid testes (Nishimune et al. 1978). I believe that the results of Martin et al. (2008) would have been more convincing if the authors could have shown that high levels of estrogens suppress spermatogenesis. The data of Martin et al. (2008) do not allow us to extrapolate whether exposure to environmental chemicals and pollutants with estrogenic or antiandrogenic effects can cause testicular “ascent” (Barthold and Gonzalez 2003). There is strong experimental evidence that prenatal exposure to environmental chemicals, including phthalate esters, is associated with an increased risk of postnatal cryptorchidism (Imajima et al. 1997). The similarity in the histopathology of the ascending testis and the testis undescended since birth suggests that ascending testes are not retractile testes trapped in scar tissue (Rusnack et al. 2002). Furthermore, this finding also suggests that, as in primary undescended testes, estrogen/antiandrogen hypotheses could explain the cause of ascending testes, because a thermal effect cannot be blamed for the decreased germ cell count in the descended testis. Overall, the systematic review and meta-analysis by Martin et al. (2008) is the most extensive attempt to date to investigate the link between estrogenic agents and testicular dysgenesis syndrome. Although some of the data from the cited studies are of limited quality, the fact that nearly all of the included studies identified an increase in the risk of hypospadias, cryptorchidism, and testicular cancer in the groups prenatally exposed to diethylstilbestrol provides strong support for that association being genuine. However, from the data of Martin et al. (2008), we cannot conclude whether exposure to environmental chemicals with estrogenic effects significantly increases the risk of developing acquired cryptorchidism. Further research to evaluate the effects of endocrine-disrupting chemicals (EDCs)—particularly those with estrogen-like effects on reproductive health—is justified and should continue.