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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.)

Background: Myofibroblastic, peritubular cells in the walls of seminiferous tubules produce low levels of the extracellular matrix (ECM) protein decorin (DCN), which has the ability to interfere with growth factor (GF) signaling. In men with impaired spermatogenesis, fibrotic remodeling of these walls and accumulation of tryptase-positive mast cells (MCs) occur., Methods: Human testicular biopsies with normal and focally impaired spermatogenesis (mixed atrophy) were subjected to immunohistochemistry and laser micro-dissection followed by RT-PCR. Primary human testicular peritubular cells (HTPCs), which originate from normal and fibrotically altered testes (HTPC-Fs), were studied by qRT-PCR, western blotting, enzyme-linked immunosorbent assay measurements and Ca(2+) imaging. Phosphorylation and viability/proliferation assays were performed., Results: Immunohistochemistry revealed DCN deposits in the walls of tubules with impaired spermatogenesis. Mirroring the situation in vivo, HTPC-Fs secreted more DCN than HTPCs (P < 0.05). In contrast to HTPCs, HTPC-Fs also responded to the main MC product, tryptase, and to a tryptase receptor (PAR-2) agonist by further increased production of DCN (P < 0.05). Several GF receptors (GFRs) are expressed by HTPCs and HTPC-Fs. DCN acutely increased intracellular Ca(2+)-levels and phosphorylated epidermal GF (EGFR) within minutes. Platelet-derived GF (PDGF) and EGF induced strong mitogenic responses in HTPC/-Fs, actions that were blocked by DCN, suggesting that DCN in the ECM interferes with GF/GFRs signaling of peritubular cells of the human testis., Conclusions: The data indicate that the increase in testicular DCN found in male infertility is a consequence of actions of MC-derived tryptase. We propose that the increases in DCN may consequently imbalance the paracrine signaling pathways in human testis.

Background: Testicular peritubular cells form an ill-characterized cellular compartment of the human testis, which forms a border with Sertoli cells and spermatogonial stem cells (SSCs). A recently developed culture method has identified parts of the secretory repertoire of human testicular peritubular cells (HTPCs), which includes nerve growth factor. Whether peritubular cells produce glial cell line-derived neurotrophic factor (GDNF) and may thus contribute to the stem cell niche is not known., Methods: We studied GDNF production in isolated peritubular cells from men with normal spermatogenesis (HTPCs) and impaired spermatogenesis and testicular fibrosis (HTPC-Fs). Human testicular biopsies and peritubular cells in culture were evaluated using immunohistochemistry, laser microdissection (LMD), RT-PCR and measurement of GDNF and cAMP by enzyme-linked immunosorbent assay. We also tested whether GDNF production is regulated by tumour necrosis factor-alpha (TNF-alpha) or tryptase, the products of mast cells or macrophages., Results: Peritubular wall cells are in close proximity to cells expressing the GDNF family co-receptor-alpha1. GDNF mRNA was detected in LMD samples of the peritubular and tubular but not interstitial compartments. HTPCs and HTPC-Fs lack FSH- and LH-receptors but express receptors for TNF-alpha and tryptase. Importantly, peritubular cells express GDNF and constitutively released GDNF into the medium in comparably high amounts. TNF-alpha and tryptase had no effect on the secretion of GDNF by HTPCs or HTPC-Fs., Conclusions: Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis.

The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that peroxisome proliferator-activated receptor-gamma is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.

Background: Radiation damage to skin is a key diagnostic and prognostic parameter for patients accidentally exposed to radiation. Moreover, skin is a target organ for crucial side-effects of routine radiotherapy. The pathophysiology of the cutaneous radiation reaction is in many respects still unknown. The acute inflammatory radiation reaction of skin has been shown to involve alterations in cell-cell and cell-matrix interactions, which are mediated by cellular adhesion molecules., Objectives: To evaluate the effect of ionizing radiation on intercellular adhesion molecule-1 (ICAM-1) expression in human skin cells., Methods: Dermal monolayer cells, a three-dimensional skin model and skin biopsies were investigated for ICAM-1 expression after ionizing radiation using flow cytometry, quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. ICAM-1 expression in monolayer cells pretreated with protein kinase inhibitors and dexamethasone prior to irradiation was analysed by flow cytometry., Results: Using different sources of skin cells, we demonstrated a consistent upregulation of both ICAM-1 mRNA and protein expression by ionizing radiation. Blocking experiments revealed that tumour necrosis factor-alpha, another ICAM-1 inducer, does not account for the effect of radiation. Radiation-induced upregulation of ICAM-1 expression was significantly attenuated by inhibitors to protein kinase C, mitogen-activated protein (MAP) ERK kinase, p38 MAP kinase and phosphatidylinositol 3-kinase. The anti-inflammatory agent dexamethasone suppressed the effect of radiation on ICAM-1 expression, suggesting its usefulness to treat the cutaneous radiation reaction., Conclusions: Our data suggest that ICAM-1 is a consistent inflammatory parameter of the cutaneous radiation reaction both in vitro and in vivo that might provide new therapeutic options for diagnosis and treatment of effects of radiation.

Context: Fibrotic remodeling, especially of the tubule wall, in testes of infertile men is common, but reasons or consequences of these striking changes are not known. Based on cell culture and ex vivo studies, we previously suggested that mast cells via their products tryptase and histamine are involved in the development of fibrosis. However, studies in a relevant human testicular model are required to further test this hypothesis and the mechanisms of testicular fibrosis in general., Objective: The objective of the study was the isolation, culture, and characterization of adult human testicular peritubular cells., Patients and Interventions: Peritubular cells were obtained from biopsies of men suffering from obstructive azoospermia (n = 8) and varicocele (n = 2) but displaying normal spermatogenesis., Results: Explant cultures were obtained from all biopsies. Immunostaining of the cultured cells and corresponding paraffin-embedded tissues with antibodies against markers of fibroblasts (CD90/Thy-1) and smooth muscle cells (alpha-smooth muscle actin) clearly proved their origin from the peritubular region. These cells displayed morphological features of myofibroblasts, and gene array analyses as well as immunohistochemistry revealed the predominant expression of extracellular matrix genes and genes coding for basement membrane components. The cultured cells retain receptors for the major mast cell products histamine and tryptase. The addition of histamine (100 microm) and the tryptase agonist peptide SLIGKV (10 microm) resulted in a transient increase in intracellular calcium levels, confirming the functionality of the receptors., Conclusions: We conclude that human peritubular cells are a novel model for the investigation of paracrine, including mast cell initiated, interactions in the human testis, which will allow the study of fibrotic processes underlying male idiopathic infertility.

A new indication for testicular tissue cryopreservation is demonstrated in a patient with metachronous bilateral testicular tumours and azoospermia. At the age of 18 (1982) the patient underwent left orchidectomy and radical retroperitoneal lymphadenectomy for a testicular teratoma (pT1N0M0). Semen samples were not cryopreserved because of absence of motile spermatozoa after thawing. Seventeen years after the primary testicular cancer, a seminoma of the contralateral right testis was diagnosed (pT1N0M0). Since the patient was azoospermic, no semen samples could be cryopreserved. However, spermatozoa were detected in testicular biopsy material of the right testis and were cryopreserved for ICSI. Since all spermatozoa were dead after thawing, testicular sperm extraction (TESE) was performed in the remaining tissue samples at the time of ICSI treatment. Only spermatids could be extracted from frozen-thawed samples due to the inhomogeneous distribution of spermatogenic activity in the testicular tissue. Although one oocyte was fertilized with these spermatids, a clinical pregnancy was not achieved. Despite the disappointing results of ICSI in the couple presented here, this case report demonstrates that cryopreservation of testicular tissue and TESE should be considered in patients with bilateral testicular tumours and azoospermia, if frozen semen samples are not available.

In order to evaluate a possible paternal age effect, testicular sperm cells from three men aged 81, 82, and 83 yr were analyzed by two-color- and three-color-fluorescence in situ hybridization for disomy rates of chromosomes 1, 17, 18, X, and Y as well as for diploidy frequencies. A minimum of 1500 sperm cells per donor and probe was evaluated due to the low number of spermatozoa in the preparations. Diploidy and disomy frequencies were in the same range as found in men aged <30 yr, a slight increase only being noticed for XY nuclei.

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 membranes 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.

The acrosome reaction is an important marker for human sperm function. Since different laboratory techniques may be used for the detection of this exocytotic process, the purpose of the present study was to compare three common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and transmission electron microscopy for identification of acrosomal changes. Preliminary findings had demonstrated that similar results were achieved with Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were omitted. In various experiments, human spermatozoa were treated with two concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and 6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower than those obtained by double staining or FITC-PSA, which showed comparable results. Following 6 h of capacitation and incubation with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC-ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect different stages of the acrosome reaction and may be helpful for a differentiated evaluation of this sperm function.

Smoking and varicocele are frequent findings in the medical history and physical examination of patients attending andrological outpatient departments. However, data about their influence on human semen parameters, such as sperm concentration and motility, are contradictory. Therefore, the purpose of this study was to examine sperm function (acrosin activity and induction of the acrosome reaction) in smokers (n = 30) and varicocele patients (n = 30) compared with normal fertile donors (n = 20). The acrosome reaction was detected by triple staining after 3 h of incubation at 37 degrees C, followed by treatment with 0.1% dimethylsulphoxide (spontaneous acrosome reaction) and 10 microM calcium ionophore A23187 (induced acrosome reaction) for 1 h at 37 degrees C. Acrosin activity was measured by gelatinolysis. The diameters around the sperm heads after gelatinolysis and the percentages of spermatozoa showing halo formations were evaluated. The inducibility of the acrosome reaction was significantly lower in semen samples from smokers than in those from the fertile group (7.1 +/- 3.2 versus 11.2 +/- 4.0%, P < 0.01), whereas no statistically significant difference was demonstrated in spermatozoa from patients with varicocele (9.3 +/- 4.3%). Both the percentages of spermatozoa with halo formation (53.3 +/- 20.0 versus 76.6 +/- 13.6%, P < 0.05) and the halo diameters (16.1 +/- 6.6 versus 31.0 +/- 14.5 microns, P < 0.001) were significantly lower in the varicocele group than in the samples from fertile men. These data suggest that smoking and varicocele affect sperm function, and that the standard semen parameters alone are insufficient to evaluate the influence of both factors on human male fertility.

Tail stump syndrome, which may be associated with primary ciliary dyskinesia, is also associated with morphological defects of the flagellum resulting in severe asthenozoospermia. Until recently, these morphological anomalies caused definite male infertility. Today, however, new methods such as micromanipulation techniques provide a rational therapy for this patient group. A pregnancy followed by living offspring was achieved following the intracytoplasmic injection of immotile spermatozoa from a patient with tail stump syndrome.