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Angiotensin-converting enzyme (ACE) is known to be released from human spermatozoa during capacitation. However, it has not yet been localized ultrastructurally in ejaculated sperm cells. Therefore, the purpose of the present study was to demonstrate the location of ACE by means of immunoelectron microscopy and direct immunofluorescence. In addition, ACE activity of spermatozoa was correlated with standard semen parameters. The activity of angiotensin-converting enzyme was measured in spermatozoa from 115 donors and patients attending the andrological outpatient department. Progressive motility was negatively correlated with sperm ACE activity (Spearman rank correlation r = -0.364, P < 0.0001), whereas no statistically significant correlations with sperm concentration, total motility and morphology were observed. Immunoelectron microscopy demonstrated that ACE is mainly located at the plasma membrane of the acrosomal region, equatorial segment, postacrosomal region and midpiece. In contrast, only weak ACE-like immunoreactivity was found at the flagellum. In cases of cells with missing plasma membrane ACE seems also to be located at the surface of the outer acrosomal membrane. By means of immunohistochemical methods, different patterns of ACE-like immunofluorescence were observed: (i) fluorescence of the acrosome or the entire sperm head, midpiece and flagellum; (ii) fluorescence of the postacrosomal region, midpiece and flagellum; (iii) bright fluorescence of the equatorial segment with less intensive labelling of the postacrosomal region and flagellum. Induction of the acrosome reaction by calcium ionophore A23187 resulted in an increase of spermatozoa with weak acrosomal fluorescence, indicating loss of the plasma membrane. [ABSTRACT FROM PUBLISHER]

Human testicular peritubular cells (HTPCs) are smooth muscle cells, which in the testis form a small compartment surrounding the seminiferous tubules. Contractions of HTPCs are responsible for sperm transport, HTPCs contribute to spermatogenesis, have immunological roles and are a site of glucocorticoid receptor expression. Importantly, HTPCs maintain their characteristics in vitro, and thus can serve as an experimental window into the male gonad. Previously we reported consequences of 3-day treatment with Dexamethasone (Dex), a synthetic glucocorticoid and multi-purpose anti-inflammatory drug. However, as glucocorticoid therapies in man often last longer, we now studied consequences of a prolonged 7-day exposure to 1 µM Dex. Combining live cell imaging with quantative proteomics of samples taken from men, we confirmed our recent findings but more importantly, found numerous novel proteomic alterations induced by prolonged Dex treatment. The comparison of the 7-day treatment with the 3-day treatment dataset revealed that extracellular matrix- and focal adhesion-related proteins become more prominent after 7 days of treatment. In contrast, extended stimulation is, for example, associated with a decrease of proteins related to cholesterol and steroid metabolism. Our dataset, which describes phenotypic and proteomic alterations, is a valuable resource for further research projects investigating effects of Dex on human testicular cells., (© 2024 The Authors. PROTEOMICS published by Wiley‐VCH GmbH.)

Testicular adrenal rest tumors and adrenogenital syndrome (AGS) - Do not mix up with malignant testicular tumors! Testicular adrenal residual tumors (TARTs) frequently occur in men with adrenogenital syndrome. Without knowledge of AGS, diagnosis is problematic due to difficult differentiation from other testicular tumors. However, early treatment is crucial for maintaining or regaining fertility, among other aspects. This article provides background knowledge for general practitioners., (© 2024. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The identification of potential environmental hazards is of clinical relevance for the diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproduction. Reproductive toxicity may evolve at the hypothalamic-pituitary, testicular, or posttesticular level; endpoints comprise deterioration of spermatogenesis and sperm function as well as endocrine disorders and sexual dysfunction. However, due to the complex regulation of the male reproductive system, information regarding single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal or in vitro studies remains difficult. Nevertheless, the assessment of relevant exposures to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The functions of human testicular peritubular cells (HTPCs), forming a small compartment located between the seminiferous epithelium and the interstitial areas of the testis, are not fully known but go beyond intratesticular sperm transport and include immunological roles. The expression of the glucocorticoid receptor (GR) indicates that they may be regulated by glucocorticoids (GCs). Herein, we studied the consequences of the GC dexamethasone (Dex) in cultured HTPCs, which serves as a unique window into the human testis. We examined changes in cytokines, mainly by qPCR and ELISA. A holistic mass-spectrometry-based proteome analysis of cellular and secreted proteins was also performed. Dex, used in a therapeutic concentration, decreased the transcript level of proinflammatory cytokines, e.g., IL6 , IL8 and MCP1 . An siRNA-mediated knockdown of GR reduced the actions on IL6. Changes in IL6 were confirmed by ELISA measurements. Of note, Dex also lowered GR levels. The proteomic results revealed strong responses after 24 h (31 significantly altered cellular proteins) and more pronounced ones after 72 h of Dex exposure (30 less abundant and 42 more abundant cellular proteins). Dex also altered the composition of the secretome (33 proteins decreased, 13 increased) after 72 h. Among the regulated proteins were extracellular matrix (ECM) and basement membrane components (e.g., FBLN2, COL1A2 and COL3A1), as well as PTX3 and StAR. These results pinpoint novel, profound effects of Dex in HTPCs. If transferrable to the human testis, changes specifically in ECM and the immunological state of the testis may occur in men upon treatment with Dex for medical reasons.

Background As the COVID-19 pandemic persists and new vaccines are developed, concerns among the general public are growing that both infection with the SARS-CoV-2 virus and vaccinations against the coronavirus (mRNA vaccines) could lead to infertility or higher miscarriage rates. These fears are voiced particularly often by young adults of reproductive age. This review summarizes the current data on the impact of SARS-CoV-2 infection and corona vaccinations on female and male fertility, based on both animal models and human data. Method A systematic literature search (PubMed, Embase, Web of Science) was carried out using the search terms "COVID 19, SARS-CoV-2, fertility, semen, sperm, oocyte, male fertility, female fertility, infertility". After the search, original articles published between October 2019 and October 2021 were selected and reviewed. Results Despite the use of very high vaccine doses in animal models, no negative impacts on fertility, the course of pregnancy, or fetal development were detected. In humans, no SARS-CoV-2 RNA was found in the oocytes/follicular fluid of infected women; similarly, no differences with regard to pregnancy rates or percentages of healthy children were found between persons who had recovered from the disease, vaccinated persons, and controls. Vaccination also had no impact on live-birth rates after assisted reproductive treatment. No viral RNA was detected in the semen of the majority of infected or still infectious men; however, a significant deterioration of semen parameters was found during semen analysis, especially after severe viral disease. None of the studies found that corona vaccines had any impact on male fertility. Discussion Neither the animal models nor the human data presented in recent studies provide any indications that fertility decreases after being vaccinated against coronavirus. However, there is a growing body of evidence that severe SARS-CoV-2 infection has a negative impact on male fertility and there is clear evidence of an increased risk of complications among pregnant women with SARS-CoV-2 infection. The counseling offered to young adults should therefore take their fears and concerns seriously as well as providing a structured discussion of the current data., Competing Interests: Conflict of Interest/Interessenkonflikt The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Extracellular ATP has been described to be involved in inflammatory cytokine production by human testicular peritubular cells (HTPCs). The ectonucleotidases ENTPD1 and NT5E degrade ATP and have been reported in rodent testicular peritubular cells. We hypothesized that if a similar situation exists in human testis, ATP metabolites may contribute to cytokine production. Indeed, ENTPD1 and NT5E were found in situ and in vitro in HTPCs. Malachite green assays confirmed enzyme activities in HTPCs. Pharmacological inhibition of ENTPD1 (by POM-1) significantly reduced pro-inflammatory cytokines evoked by ATP treatment, suggesting that metabolites of ATP, including adenosine, are likely involved. We focused on adenosine and detected three of the four known adenosine receptors in HTPCs. One, A2B, was also found in situ in peritubular cells of human testicular sections. The A2B agonist BAY60-6583 significantly elevated levels of IL6 and CXCL8, a result also obtained with adenosine and its analogue NECA. Results of siRNA-mediated A2B down-regulation support a role of this receptor. In mouse peritubular cells, in contrast to HTPCs, all four of the known adenosine receptors were detected; when challenged with adenosine, cytokine expression levels significantly increased. Organotypic short-term testis cultures yielded comparable results and indicate an overall pro-inflammatory action of adenosine in the mouse testis. If transferable to the in vivo situation, our results may implicate that interference with the generation of ATP metabolites or interference with adenosine receptors could reduce inflammatory events in the testis. These novel insights may provide new avenues for treatment of sterile inflammation in male subfertility and infertility., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Palmitic acid (PA) is a major fatty acid, derived from diet and endogenous production, which is being linked to inflammation. While such actions of PA at the level of the testis remain difficult to examine, we reasoned that studies in human testicular cells may be instructive. Human testicular peritubular cells (HTPCs) can be isolated from men and cultured. They have contractile properties but also produce Interleukin 6 (IL6), express the inflammasome member NLRP3, and via glia cell line derived neurotrophic factor (GDNF), they contribute to the spermatogonial stem cell niche. We found that PA at 100 µM significantly increased the levels of IL6, while NLRP3 or the related Interleukin 1 beta ( IL1beta ) were not affected. The contractility marker calponin ( CNN1 ) and the growth factor GDNF were likewise not affected. ELISA studies confirmed the stimulatory PA actions on IL6. Hence, PA derived from diet and/or endogenous sources may be able to foster a pro-inflammatory milieu in the testis. A possible link of these results to diet and high fat intake and obesity is indicated by the about 12-fold elevated testicular levels of IL6 in testes of obese rhesus monkeys ( n = 3), fed with a Western Style diet. They had elevated 2-5-fold increased body fat and increased circulating triglyceride levels. Further consequences of PA and obesity for testicular functions remain to be evaluated.

Infertility is defined as the inability of a couple to succeed in achieving a spontaneous pregnancy after 1 year. Male and female factors contribute to infertility with approximately 40% each. In the remaining cases factors that affect fertility can be found in both partners. The andrological work-up should be started simultaneously with the gynecological diagnostic procedure in order to identify and treat andrological factors related to infertility. Since the majority of intracytoplasmic sperm injection procedures are performed due to andrological infertility, andrological diagnostics can prevent a delay in assisted reproductive technology. The andrological work-up can be necessary before 12 months of unsuccessful conception if the female partner is older than 35 years or andrological factors are present that could impair male fertility.

Whether glucocorticoids (GC) can directly affect human testicular functions is not well understood. A predominant site of GC receptor (GR; NR3C1 ) expression in the adult testis are peritubular smooth muscle-like cells, which express smooth muscle actin (ACTA2), contract and thereby are involved in sperm transport. In contrast to the adult, neither GR nor ACTA2, or elastin (ELN) were detected in the peritubular compartment before puberty in non-human primate testes. In isolated human testicular peritubular cells (HTPCs), activation of GR by dexamethasone (Dex) caused the translocation of GR to the nucleus and stimulated expression of ACTA2 and ELN , without affecting the expression of collagens. Cytoskeletal ACTA2-rearrangements were observed and were associated with an increased ability to contract. Our results indicate post-pubertal testicular roles of GC in the maintenance of the contractile, smooth muscle-like phenotype of peritubular cells.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German/Austrian/Swiss interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. This guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aims One third of the causes of involuntary childlessness are still unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. At present, there is no standard treatment concept, as currently no standard multidisciplinary procedures exist for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnostic workup and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations The first part of this guideline focuses on the basic assessment of affected women, including standard anatomical and endocrinological diagnostic procedures and examinations into any potential infections. Other areas addressed in this guideline are the immunological workup with an evaluation of the patient's vaccination status, an evaluation of psychological factors, and the collection of data relating to other relevant factors affecting infertility. The second part will focus on explanations of diagnostic procedures compiled in collaboration with specialists from other medical specialties such as andrologists, human geneticists and oncologists., Competing Interests: Conflict of Interest/Interessenkonflikt The conflicts of interest of the authors are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (© Thieme Medical Publishers.)

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. The guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aim In one third of cases, the cause of involuntary childlessness remains unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. There is no standard treatment concept for these patients at present, as there are currently no standard multidisciplinary procedures for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnosis and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations This second part of the guideline describes the hematological workup for women as well as additional diagnostic procedures which can be used to investigate couples and which are carried out in cooperation with physicians working in other medical fields such as andrologists, geneticists and oncologists., Competing Interests: Conflict of Interest/Interessenkonflikt The authorsʼ conflicts of interest are listed in the long version of the guideline./Die Interessenkonflikte der Autoren sind in der Langfassung der Leitlinie aufgelistet., (© Thieme Medical Publishers.)

There is evidence for an age-related decline in male reproductive functions, yet how the human testis may age is not understood. Human testicular peritubular cells (HTPCs) transport sperm, contribute to the spermatogonial stem cell (SSC) niche and immune surveillance, and can be isolated and studied in vitro. Consequences of replicative senescence of HTPCs were evaluated to gain partial insights into human testicular aging. To this end, early and advanced HTPC passages, in which replicative senescence was indicated by increased cell size, altered nuclear morphology, enhanced β-galactosidase activity, telomere attrition and reduced mitochondrial DNA (mtDNA), were compared. These alterations are typical for senescent cells, in general. To examine HTPC-specific changes, focused ion beam scanning electron microscopy (FIB/SEM) tomography was employed, which revealed a reduced mitochondrial network and an increased lysosome population. The results coincide with the data of a parallel proteomic analysis and indicate deranged proteostasis. The mRNA levels of typical contractility markers and growth factors, important for the SSC niche, were not significantly altered. A secretome analysis identified, however, elevated levels of macrophage migration inhibitory factor (MIF) and dipeptidyl peptidase 4 (DPP4), which may play a role in spermatogenesis. Testicular DPP4 may further represent a possible drug target.

Introduction: Although low sexual desire is 1 of the most common sexual dysfunctions in men, there is a lack of studies investigating associated factors in large, population-based samples of middle-aged men., Aim: To survey the prevalence of low sexual desire in a population-based sample of 45-year-old German men and to evaluate associations with a broad set of factors., Methods: Data were collected between April 2014-April 2016 within the German Male Sex-Study. Participants were asked to fill out questionnaires about 6 sociodemographic, 5 lifestyle, and 8 psychosocial factors, as well as 6 comorbidities and 4 factors of sexual behavior. Simple and multiple logistic regressions were used to assess potential explanatory factors., Main Outcome Measures: We found a notable prevalence of low sexual desire in middle-aged men and detected associations with various factors., Results: 12,646 men were included in the analysis, and prevalence of low sexual desire was 4.7%. In the multiple logistic regression with backward elimination, 8 of 29 factors were left in the final model. Men having ≥2 children, higher frequency of solo-masturbation, perceived importance of sexuality, and higher sexual self-esteem were less likely to have low sexual desire. Premature ejaculation, erectile dysfunction, and lower urinary tract symptoms were associated with low sexual desire., Clinical Implications: Low sexual desire is common in middle-aged men, and associating factors that can potentially be modified should be considered during assessment and treatment of sexual desire disorders., Strengths & Limitations: The strength of our study is the large, population-based sample of middle-aged men and the broad set of assessed factors. However, because of being part of a prostate cancer screening trial, a recruiting bias is arguable., Conclusion: Our study revealed that low sexual desire among 45-year-old men is a common sexual dysfunction, with a prevalence of nearly 5% and might be affected by various factors, including sociodemographic and lifestyle factors, as well as comorbidities and sexual behavior. Meissner VH, Schroeter L, Köhn F-M, et al. Factors Associated with Low Sexual Desire in 45-Year-Old Men: Findings from the German Male Sex-Study. J Sex Med 2019;16:981-991., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Erectile dysfunction (ED) is a common public health issue with a significant impact on quality of life. The associations between ED and several risk factors have been reported previously. The continuously increasing incidence of these factors is contributing to the increasing prevalence of ED., Aim: To assess ED prevalence and severity in a representative sample of 45-year-old German men and to analyze the association with risk factors (lifestyle risk factors/comorbidities)., Methods: Data were collected within the German Male Sex-Study. Randomly selected 45-year-old men were invited. A total of 10,135 Caucasian, heterosexual, sexually active men were included in this analysis. The self-reported prevalence of ED was assessed using the Erectile Function domain of the International Index of Erectile Function. Risk factors for ED were ascertained using self-report questionnaires. An anamnesis interview and a short physical examination were performed., Main Outcome Measure: ED prevalence and severity were evaluated in a cross-sectional design. The associations of ED with comorbidities (eg, depression, diabetes, hypertension, lower urinary tract symptoms) and lifestyle factors (ie, smoking, obesity, central obesity, physical inactivity, and poor self-perceived health-status) were analyzed by logistic regression., Results: The overall prevalence of ED was 25.2% (severe, 3.1%; moderate, 9.2%; mild to moderate, 4.2%; mild, 8.7%). Among the men with ED, 48.8% had moderate or severe symptoms. ED prevalence increased with the number of risk factors, to as high as 68.7% in men with 5-8 risk factors. In multiple logistic regression with backward elimination, the strongest associations with ED were found for depression (odds ratio [OR] = 1.87), poor self-perceived health status (OR = 1.72), lower urinary tract symptoms (OR = 1.68), and diabetes (OR = 1.38)., Conclusion: One out of 4 men already had symptoms of ED at age 45. Almost one-half of the men with ED had moderate to severe symptoms. ED was strongly associated with each analyzed risk factor, and the prevalence and severity of ED increased with an increasing number of risk factors. Hallanzy J, Kron M, Goethe VE, et al. Erectile Dysfunction in 45-Year-Old Heterosexual German Men and Associated Lifestyle Risk Factors and Comorbidities: Results From the German Male Sex Study. Sex Med 2019;7:26-34., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The identification of potential environmental hazards may be clinically relevant in the diagnosis of male infertility. Knowledge about these factors will improve prevention of fertility disorders. Apart from drugs or factors related to lifestyle such as alcohol and tobacco smoke, various environmental and occupational agents, both chemical and physical, may impair male reproductive function. Reproductive toxicity may evolve at the hypothalamic-pituitary, testicular, or post-testicular level; endpoints comprise deterioration of spermatogenesis and sperm function as well as endocrine disorders and sexual dysfunction. With regard to the complex regulation of the male reproductive system, the available information concerning single exogenous factors and their mechanisms of action in humans is limited. This is also due to the fact that extrapolation of results obtained from experimental animal or in vitro studies remains difficult. Nevertheless, the assessment of relevant exposure to reproductive toxicants should be carefully evaluated during diagnostic procedures of andrological patients.

Stress activates the sympathetic nervous system and is linked to impaired fertility in man. We hypothesized that catecholamines by acting on testicular cells have a role in these events, possibly by fostering an inflammatory environment. The cells of the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), express adrenergic receptors (ADRs) α1B, α1D, β1 and β2. A selective α1-ADR agonist, phenylephrine, increased intracellular Ca 2+ -levels in cultured HTPCs and induced COX-2, IL-6 and MCP-1 mRNA expression without affecting IL-1β mRNA. These changes were paralleled by a significant increase in the secretion of IL-6 and MCP-1. Epinephrine was also effective, but salbutamol, a selective β2-ADR agonist was not. Our results suggest that stress-associated elevation of catecholamines may be able to promote inflammatory events by targeting peritubular cells in the human testis. Blockage of α1-ADRs may therefore be a novel way to interfere with stress-related impairment of male reproductive functions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Peritubular cells are part of the wall of seminiferous tubules in the human testis and their contractile abilities are important for sperm transport. In addition, they have immunological roles. A proteomic analysis of isolated human testicular peritubular cells (HTPCs) revealed expression of the transient receptor potential channel subfamily V member 2 (TRPV2). This cation channel is linked to mechano-sensation and to immunological processes and inflammation in other organs. We verified expression of TRPV2 in peritubular cells in human sections by immunohistochemistry. It was also found in other testicular cells, including Sertoli cells and interstitial cells. In cultured HTPCs, application of cannabidiol (CBD), a known TRPV2 agonist, acutely induced a transient increase in intracellular Ca 2+ levels. These Ca 2+ transients could be blocked both by ruthenium red, an unspecific Ca 2+ channel blocker, and tranilast (TRA), an antagonist of TRPV2, and were also abolished when extracellular Ca 2+ was removed. Taken together this indicates functional TRPV2 channels in peritubular cells. When applied for 24 to 48 h, CBD induced expression of proinflammatory factors. In particular, mRNA and secreted protein levels of the proinflammatory chemokine interleukin-8 (IL-8/CXCL8) were elevated. Via its known roles as a major mediator of the inflammatory response and as an angiogenic factor, this chemokine may play a role in testicular physiology and pathology.

In man, blockage of prostaglandin (PG)-production e.g. by non-steroidal anti-inflammatory drug (NSAIDs) may have negative testicular side effects, implying beneficial actions of PGs in the testis. We examined human testicular samples and isolated human testicular peritubular cells (HTPCs) to explore sites of PG-synthesis and targets. HTPCs express cyclooxygenase 1 (COX1) and secrete PGE 2 . Receptors (EP1, 2, 4) were specifically identified in peritubular cells. In HTPCs PGE 2 significantly increased mRNA levels of the contractility protein calponin, but did not induce contractions. PGE 2 , as well as EP1 and EP4 receptor agonists, significantly increased glia cell line derived neurotrophic factor (GDNF) mRNA and/or protein levels. Importantly, the NSAID ibuprofen reduced PGE 2 and this action also lowered SMA and calponin mRNA levels and levels of secreted GDNF protein. The results reveal an unknown PGE 2 system in the human testis, in involving peritubular cells, which may be prone to interference by NSAIDs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

NLRP3 is part of the NLRP3 inflammasome and a global sensor of cellular damage. It was recently discovered in rodent Sertoli cells. We investigated NLRP3 in mouse, human and non-human primate (marmoset and rhesus macaque) testes, employing immunohistochemistry. Sertoli cells of all species expressed NLRP3, and the expression preceded puberty. In addition, peritubular cells of the adult human testes expressed NLRP3. NLRP3 and associated genes ( PYCARD , CASP1 , IL1B ) were also found in isolated human testicular peritubular cells and the mouse Sertoli cell line TM4. Male infertility due to impairments of spermatogenesis may be related to sterile inflammatory events. We observed that the expression of NLRP3 was altered in the testes of patients suffering from mixed atrophy syndrome, in which tubules with impairments of spermatogenesis showed prominent NLRP3 staining. In order to explore a possible role of NLRP3 in male infertility, associated with sterile testicular inflammation, we studied a mouse model of male infertility. These human aromatase-expressing transgenic mice ( AROM+ ) develop testicular inflammation and impaired spermatogenesis during aging, and the present data show that this is associated with strikingly elevated Nlrp3 expression in the testes compared to WT controls. Interference by aromatase inhibitor treatment significantly reduced increased Nlrp3 levels. Thus, throughout species NLRP3 is expressed by somatic cells of the testis, which are involved in testicular immune surveillance. We conclude that NLRP3 may be a novel player in testicular immune regulation., (© 2018 Society for Reproduction and Fertility.)

Contractile smooth muscle-like peritubular cells build the wall of seminiferous tubules in men. They are crucial for sperm transport and complement the functions of Sertoli cells by secreting factors, including glial cell line-derived neurotrophic factor. Previous studies revealed that they also secrete the chemokine C-X-C motif chemokine ligand 12 (CXCL12), which has known roles in spermatogenesis. Peritubular cells express the androgen receptor (AR), which is retained in isolated human testicular peritubular cells. We aimed to explore AR-regulated functions in human testicular peritubular cells. Bearing in mind that infertile men often have high aromatase activity, which may lower intratesticular androgen concentrations, an animal model for male infertility was studied. These mice display an age-dependent loss in spermatogenesis due to high aromatase activity. Human testicular peritubular cells were exposed to dihydrotestosterone or the antiandrogen flutamide. We studied AR, smooth muscle cell markers, glial cell line-derived neurotrophic factor and 15 secreted factors previously identified, including CXCL12. We used qPCR, Western blotting, ELISA or selected reaction monitoring (SRM). In the animal model for male infertility, we employed qPCR and immunohistochemistry. Dihydrotestosterone increased AR and flutamide prevented these actions. The smooth muscle cell markers calponin and smooth muscle actin were likewise increased, while cell size or cellular proliferation was not changed. Dihydrotestosterone did not increase glial cell line-derived neurotrophic factor or CXCL12 secretion but increased levels of serine proteinase inhibitor (SERPIN) E1. The animal model for male infertility with high aromatase activity showed reduced numbers of AR-immunoreactive testicular peritubular cells, suggesting that altered androgen and/or oestrogen levels could influence AR-mediated responses in peritubular cells. Androgens act on human testicular peritubular cells to enhance AR levels, their contractile phenotype and to modulate the secretion of some secreted factors. This study suggests that some aspects of human peritubular cell functions are regulated by androgens., (© 2018 American Society of Andrology and European Academy of Andrology.)

Study Question: Are monkey testicular peritubular cells (MKTPCs) from the common marmoset monkey (Callithrix jacchus) a suitable translational model for the study of human testicular peritubular cells (HTPCs)?, Summary Answer: MKTPCs can be isolated and propagated in vitro, retain characteristic markers for testicular peritubular cells and their proteome strongly (correlation coefficient of 0.78) overlaps with the proteome of HTPCs., What Is Known Already: Smooth-muscle-like peritubular cells form the wall of seminiferous tubules, transport sperm, are immunologically active, secrete a plethora of factors and may contribute to the spermatogonial stem cell niche. Mechanistic studies are hampered by heterogeneity of human samples., Study Design, Size, Duration: We established a culture method for MKTPCs and characterized these cells from six young adult animals (2-3 years). To examine whether they qualify as a translational model we also examined HTPCs from seven men and compared the proteomes of both groups., Participants/materials, Setting, Methods: We used explant cultures to obtain MKTPCs, which express smooth muscle markers (calponin (CNN1), smooth muscle actin (ACTA2)), lack FSH-receptors (FSHR) and LH-receptors (LHCGR), but possess androgen receptors (AR). MKTPCs can be passaged at least up to eight times, without discernable phenotypic changes. Mass-spectrometry-based analyses of the MKTPC and HTPC proteomes were performed., Main Results and the Role of Chance: We established a method for isolation and cultivation of MKTPCs, and provide a comprehensive analysis of their protein repertoire. The results let us conclude that MKTPCs are suitable as a non-human primate model to study peritubular cell functions., Large Scale Data: List of identified proteins in MKTPCs by liquid chromatography-tandem mass spectrometry is accessible at the ProteomeXchange (identifier PXD009394)., Limitations, Reason for Caution: This is an in vitro cellular non-human primate model used to provide a window into the role of these cells in the human testis., Wider Implications of the Findings: Previous studies with HTPCs from patients revealed a degree of heterogeneity, possibly due to age, lifestyle and medical history of the individual human donors. We anticipate that the new translational model, derived from young healthy non-human primates, may allow us to circumvent these issues and may lead to a better understanding of the role of peritubular cells., Study Funding and Competion of Interest(s): This work was supported by grants from the Deutsche Forschungsgemeinschaft (MA 1080/27-1; AR 362/9-1; BE 2296/8-1). The authors declare no competing financial interests.

Aim: The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline., Methods: This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40)., Recommendations: The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.

Penile cancer is often an obvious visual diagnosis but histologic verification should be obtained prior to treatment. The clinical examination should determine the tumor stage and whether it has infiltrated the cavernous bodies and/or the urethra and it should adequately assess the inguinal lymph nodes. Preoperative imaging of the lesion is only indicated in equivocal cases. Curative treatment requires the complete removal of the primary tumor and all metastatic lymph nodes. Lymph node management is the key prognostic factor in the treatment of penile cancer. No imagining technique such as the ultrasound, CT, MRI or PET/CT is able to adequately detect micrometastatic lymph nodes. Therefore, invasive (inguinal) lymph node diagnosis is indicated for all tumour stages from pT1G2. Over 90% of penile cancer cases can be cured with early diagnosis and adequate treatment if routine self-examination and physical examinations are regularly performed.

Peritubular myoid cells, which form the walls of seminiferous tubules in the testis, are functionally unexplored. While they transport sperm and contribute to the spermatogonial stem cell niche, specifically their emerging role in the immune surveillance of the testis and in male infertility remains to be studied. Recently, cytokine production and activation of Toll-like receptors (TLRs) were uncovered in cultured peritubular cells. We now show that human peritubular cells express purinergic receptors P2RX4 and P2RX7, which are functionally linked to TLRs, with P2RX4 being the prevalent ATP-gated ion channel. Subsequent ATP treatment of cultured peritubular cells resulted in up-regulated (pro-)inflammatory cytokine expression and secretion, while characteristic peritubular proteins, that is smooth muscle cell markers and extracellular matrix molecules, decreased. These findings indicate that extracellular ATP may act as danger molecule on peritubular cells, able to promote inflammatory responses in the testicular environment.