Identification of molecular biomarkers associated with disease progression in the testis of bulls infected with Besnoitia besnoiti.

Breeding bulls infected with Besnoitia besnoiti may develop sterility during either acute or chronic infection. The aim of this study was to investigate the molecular pathogenesis of B. besnoiti infection with prognosis value in bull sterility. Accordingly, five well-characterized groups of naturally and experimentally infected males were selected for the study based on clinical signs and lesions compatible with B. besnoiti infection, serological results and parasite detection. A broad panel of molecular markers representative of endothelial activation and fibrosis was investigated and complemented with a histopathological approach that included conventional histology and immunohistochemistry. The results indicated the predominance of an intense inflammatory infiltrate composed mainly of resident and recruited circulating macrophages and to a lesser extent of CD3+ cells in infected bulls. In addition, a few biomarkers were associated with acute, chronic or subclinical bovine besnoitiosis. The testicular parenchyma showed a higher number of differentially expressed genes in natural infections (acute and chronic infections) versus scrotal skin in experimental infections (subclinical infection). In subclinical infections, most genes were downregulated except for the CCL24 and CXCL2 genes, which were upregulated. In contrast, the acute phase was mainly characterized by the upregulation of IL-1α, IL-6 and TIMP1, whereas in the chronic phase, the upregulation of ICAM and the downregulation of MMP13, PLAT and IL-1α were the most relevant findings. Macrophages could be responsible for the highest level of gene regulation in the testicular parenchyma of severely affected and sterile bulls, and all these genes could be prognostic markers of sterility.

Cellular basis of ClC-2 Cl- channel-related brain and testis pathologies.

The ClC-2 chloride channel is expressed in the plasma membrane of almost all mammalian cells. Mutations that cause the loss of ClC-2 function lead to retinal and testicular degeneration and leukodystrophy, whereas gain-of-function mutations cause hyperaldosteronism. Leukodystrophy is also observed with a loss of GlialCAM, a cell adhesion molecule that binds to ClC-2 in glia. GlialCAM changes the localization of ClC-2 and opens the channel by altering its gating. We now used cell type-specific deletion of ClC-2 in mice to show that retinal and testicular degeneration depend on a loss of ClC-2 in retinal pigment epithelial cells and Sertoli cells, respectively, whereas leukodystrophy was fully developed only when ClC-2 was disrupted in both astrocytes and oligodendrocytes. The leukodystrophy of Glialcam-/- mice could not be rescued by crosses with Clcn2op/op mice in which a mutation mimics the "opening" of ClC-2 by GlialCAM. These data indicate that GlialCAM-induced changes in biophysical properties of ClC-2 are irrelevant for GLIALCAM-related leukodystrophy. Taken together, our findings suggest that the pathology caused by Clcn2 disruption results from disturbed extracellular ion homeostasis and identifies the cells involved in this process.

Male infertility due to testicular disorders.

CONTEXT: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date. EVIDENCE ACQUISITION: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail. EVIDENCE SYNTHESIS/RESULTS: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking. CONCLUSIONS: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in "idiopathic" male infertility and long-term follow-up studies of babies conceived through ART.

Cadmium as a testicular toxicant: A Review.

Cadmium (Cd) is a toxic heavy metal with no known biological functions in the human body. Due to a considerably long biological half-life and very low rate of excretion, accumulation of Cd in different body organs (eg, liver, kidney, and testes) over time is associated with perturbed functioning of these organs. Recent studies have shown the extreme sensitivity of the testes to Cd toxicity. In testes, Cd has been reported to induce oxidative stress, apoptosis of spermatogenic cells, reduction in androgen production and sperm functions. Moreover, Cd in combination with other environmental toxicants may be responsible for the declining fertility of males in both animals and humans. Pinpointing how Cd toxicity affects various testicular processes will be imperative for the development of preventative measures to promote fertility among males. Therefore, in the present review, we summarize the recent findings related to the Cd-induced oxidative toxicity, apoptotic toxicity, steroidogenic toxicity, and spermatotoxicity, along with their possible mechanisms in testicular tissue of different animal species. In addition, the utilization of various antioxidant compounds, medicinal plants and other compounds for the management of Cd toxicity in testes is discussed.

Generating adverse outcome pathway (AOP) of inorganic arsenic-induced adult male reproductive impairment via integration of phenotypic analysis in comparative toxicogenomics database (CTD) and AOP wiki.

BACKGROUND: Inorganic arsenic (iAs) is a worldwide environmental pollutant which exerts complicated and various toxic effects in organisms. Increasingly epidemic studies have revealed the association between iAs exposure and adult male reproductive impairment. Consistent with the proposal for toxicity testing in the 21st century (TT21C), the adverse outcome pathway (AOP) framework may help unravel the iAs-caused molecular and functional changes leading to male reproductive impairment. METHOD: Combining CTD's phenotype-disease inference data, iAs-phenotypes were anchored to five male reproductive diseases induced by iAs, and local network topological algorithm was applied in prioritizing their interference significance. Through integrating analysis in AOP Wiki knowledge base, filtered phenotypes were linked to key events consisting of AOPs and assembled together based on evidentially upstream and downstream relationships. RESULTS: A subset of 655 phenotypes were filtered from CTD as potential key events and showed a significant coherence in five reproductive diseases wherein 39 significant phenotypes showed a good clustering features involving cell cycle, ROS and mitochondria function. Two AOP subnetworks were enriched in AOP Wiki where testosterone reduction and apoptosis of sperm served as focus events respectively. Besides, a candidates list of molecular initialing events was provided of which glucocorticoid receptor activation was overall assessed as an example. CONCLUSION: This study applied computational and bioinformatics methods in generating AOPs for arsenic reproductive toxicity, which identified the imperative roles of testosterone reduction, response to ROS, spermatogenesis and provided a global view about their internal association. Furthermore, this study helped address the existing knowledge gaps for future experimental verification.

Polyorquidism: case report comparing ultrasonography and magnetic resonance imaging / Poliorquidismo: relato de caso comparando a ultrassonografia e a ressonância magnética

Abstract Introduction: polyorchidism is an unusual pathology, about 200 cases in the world literature. Case report: we reported a case of polyorchidism in a 16-year-old male patient diagnosed by ultrasound and confirmed by magnetic resonance imaging. Discussion: most of the cases presented, there is a supernumerary testis, but there are reports on more than three, up to five testicles with supranumerical gonads on both sides of the scrotum. The diagnosis is usually performed in late puberty, incidentally, with a painless scrotal mass or at the emergency room, presenting a testicular torsion of the whole hemiscrotum or supernumerary testisalone, and the differential diagnosis should be made with epididymal cyst and spermatocele, besides other extra-testicular masses (hydroceles, varicoceles, lipomas, tumors.) and para-testicular masses (hernias, scrotal calculi). After the initial clinical evaluation, ultrasound is the first line subsidiary exam. Magnetic Resonance Imaging is very helpful, just in case the ultrasound diagnosis is uncertain. The supernumerary testishave the same Magnetic Resonance Imaging characteristics as the normal testes (intermediate signal intensity on T1- weighted images and high signal intensity on T2-weighted images).

Resumo Introdução: o poliorquidismo é uma patologia incomum, contando cerca de 200 casos na literatura mundial. Relato de caso: relatamos um caso de poliorquidismo em um paciente do sexo masculino de 16 anos, diagnosticado por ultrassom e confirmado por ressonância magnética. Discussão: na maioria dos casos apresentados, há um testículo supranumérico, mas há relatos de mais de três, até cinco testículos, com gônadas supranuméricas em ambos os lados do escroto. O diagnóstico geralmente é feito no final da puberdade, aliás, com massa escrotal indolor ou no pronto-socorro, apresentando torção de todo o hemiscroto ou somente do testículo supranumerário, e o diagnóstico diferencial deve ser feito com cisto epididimário e espermatocele, além de outros massas extratesticulares (hidroceles, varicoceles, lipomas, tumores) e massas paratesticulares (hérnias, cálculos escrotais). Após a avaliação clínica inicial, o ultrassom é a primeira linha do exame subsidiário. A ressonância magnética é muito útil se o diagnóstico por ultrassom não for certo. Os testículos supranumerários têm as mesmas características de ressonância magnética que os testículos normais (intensidade do sinal intermediário nas imagens ponderadas em T1 e alta intensidade do sinal nas imagens ponderadas em T2).

Testicular Microlithiasis Is Associated with Impaired Spermatogenesis in Patients with Unexplained Infertility.

INTRODUCTION: Testicular microlithiasis (TML) was shown to be associated with an increased risk of infertility. However, the association of TML with spermatogenesis in patients with unexplained infertility is still unknown. In this study, we therefore investigated the effect of TML on hormones and sperm parameters in a large cohort of infertile men without major factors for impaired fertility and azoospermic men serving for comparison. METHODS: Over a period of 10 years, we retrospectively analyzed 2,914 patients who attended our centre with the diagnosis of unexplained infertility and sperm count >1 million/ejaculate, as well as 281 patients with unexplained azoospermia. From the 2,914 patients, we identified 218 patients with TML as revealed by ultrasound imaging. Further, 26 out of 281 azoospermic patients showed TML. Subsequently, we performed a thorough analysis of reproductive parameters and their association with TML. RESULTS: The overall incidence of TML in patients with unexplained infertility and in unexplained azoospermic men was 7.5 and 9.3%, respectively. Patients with unexplained infertility and TML showed significantly smaller testicular volume, elevated FSH level, and lower sperm count and motility. Impaired spermatogenesis was not associated with the amount of microlithiasis, considered after classification into subgroups (<5 vs. ≥5 microliths/testis), and instead was associated with presence or absence of TML. TML in unexplained infertile azoospermic patients was not significantly associated neither with andrological reproductive parameters nor with sperm retrieval rate in microsurgical testicular sperm extraction. DISCUSSION/CONCLUSION: TML itself, and not the number of microliths, is associated with impaired spermatogenesis in patients with unexplained infertility. The parameter TML alone is not sufficient to predict spermatogenic impairment in azoospermic patients. This study highlights the importance of ultrasound imaging in the clinical evaluation of infertile men, taking into account that TML is a negative co-factor for male fertility.

Ketogenic diet improves and restores redox status and biochemical indices in monosodium glutamate-induced rat testicular toxicity.

This study investigated the effect of ketogenic diet on monosodium glutamate (MSG)-induced testicular dysfunction. Forty-six male rats (180 ±â€¯40 g) were grouped into two groups (23 rats each); control group and MSG-induced group (4 mg/kg bw) for 28 days. At the 29th day, 5 rats from both group were sacrificed to establish testicular dysfunction. The remaining animals from the control group was further divided into three sub-groups and treated for 42 days; untreated group, ketogenic diet only and curcumin only as the standard drug (150 mg/kg bw). In the pre-treatment, the administration of MSG resulted in a significant (p < 0.05) decrease in the testis-body weight ratio, alkaline phosphatase (ALP), acetylcholine esterase (AChE), cholesterol, triglycerides (TG), nitric oxide (NO), glycogen, protein and antioxidant enzymes in the testis. In the post treatment, the MSG only group significantly reduced testicular cholesterol, catalase (CAT) and NO. In contrast, MSG + ketogenic diet group showed a significant increase in levels of rat testicular acid phosphatase (ACP), ALP, cholesterol, HMG-CoA, TG, malondialdehyde (MDA), reduced glutathione (GSH) and NO. The ketogenic diet showed a significant increase (p < 0.05) in the levels of NO, ALP, cholesterol, HMG CoA reductase and (TG). In addition, significant increases in levels of rat testicular ACP, ALP, HMG-CoA, (CAT), SOD and GSH were recorded for MSG + Curcumin group. Taken together, the findings support the prospects of ketogenic diet to enhance the testicular function in rats.

Cystic Dysplasia of the Rete Testis: Does Pathophysiology Guide Management?

Cystic dysplasia of the rete testis (CDT) is a rare, benign, cause of testicular mass in the pediatric population. The mass appears on sonography as multiple small cysts of varying size surrounded by normal or compressed testicular tissue. CDT is often associated with other genitourinary anomalies, commonly presenting with agenesis or dysplasia of the ipsilateral kidney. The pathophysiology and the management remains controversial. We report a case of a 3-year-old presenting with an enlarged testicular mass later presumed to be CDT associated with ipsilateral renal agenesis, review the literature, and propose an evaluation and management algorithm.

Frequent testicular involvement in multibacillary leprosy.

OBJECTIVE: Testicular involvement or atrophy in leprosy is silent, unreported, and under-estimated. The aim of this study was to assess the frequency of testicular atrophy and its consequences through the examination of clinical manifestations, hormonal profile, and semen analysis in leprosy patients. METHODS: A descriptive observational study using a cross-sectional design and consecutive sampling method was conducted from May to July 2018. The study was conducted in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia and included 32 men affected by leprosy and five healthy men as a control group. All patients were subjected to history-taking, dermatological and genital examinations, assessment of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, and testicular ultrasonography examination. Semen analysis was performed for the 10 patients who consented. RESULTS: Testicular atrophy was observed in 93.75% of patients. Clinical manifestations of testicular atrophy were loss of libido (21.87%), female pubic hair pattern (9.38%), gynecomastia (6.25%), and secondary infertility (6.25%). Hormonal imbalance was seen in 16 patients, and all 10 patients who underwent semen analysis showed an abnormality. CONCLUSIONS: This study showed a high frequency of testicular atrophy, but the symptoms were only present in a few of patients. The assessment of testicular function should be recommended as a routine work-up for leprosy patients.

Correction of diabetes-induced testicular dysfunction by a hydro-methanol (60:40) extract of Curcuma amada rhizomes: A dose-dependent study.

Diabetes affects the reproductive system. This study was conducted to find out the potent dose of the hydro-methanol 60:40 extract of Curcuma amada rhizomes for the management of diabetes-induced testicular dysfunction in albino rats. The extract was administered at the doses of 10, 20, 40, and 80 mg/100 g body weight/day for 28 days. Oxidative stresses, reproductive parameters, histological, and gene expressions of the testicular tissue were assessed. Out of the doses used, the 20-mg dose showed maximum recovery as the minimum dose (e.g., sperm motility 112.03%, testicular cholesterol 34.86%, Bax gene expression 49.77%), whereas 40- and 80-mg doses did not vary statistically with each other (e.g., sperm motility 95.37% and 89.19%, testicular cholesterol 30.42% and 28.41%, Bax gene expression 47.33% and 46.18%, respectively) as well as with the 20-mg dose. It may be concluded that the 20-mg dose is the threshold dose for this purpose. PRACTICAL APPLICATIONS: The hydro-methanol 60:40 extract of rhizomes of Curcuma amada has a strong antioxidant property that can manage diabetes-induced oxidative injuries in testes which may raise a hope to the pharmaceutical industries to develop a herbal drug for diabetes-linked testicular hypofunction management.

MitoQ ameliorates testis injury from oxidative attack by repairing mitochondria and promoting the Keap1-Nrf2 pathway.

Mitochondrial dysfunctions induced by oxidative stress could play a pivotal role in the development of testicular damage and degeneration, leading to impaired fertility in adulthood. MitoQ as mitochondria-targeted antioxidant has been used in many diseases for a long time, but its therapeutic effects on testicular injury 'have not been reported yet. Here, we examined the protective action mechanism of MitoQ on testicular injury from oxidative stress induced by triptolide (TP). Mice were orally administrated with MitoQ (1.3, 2.6 and 5 .2mg/kg, respectively) in a TP-induced model of testicular damage for 14 days. And then testis injuries were comprehensively evaluated in terms of morphological changes, spermatogenesis assessment, blood-testis barrier (BTB) integrity, and apoptosis. The results demonstrated MitoQ effectively increased testicular weight, maintained the integrity of BTB, protected microstructure of testicular tissue and sperm morphology by inhibition of oxidative stress. Further mechanism studies revealed that MitoQ markedly activates the Keap1-Nrf2 antioxidative defense system characterized by increasing the expression of Nrf2 and its target genes HO-1 and NQO1. Meanwhile, MitoQ upregulated the expression of mitochondrial dynamics proteins Mfn2 and Drp-1and exerted a protective effect on mitochondria. On this basis, the results from pharmacokinetic study indicated that the MitoQ could enter into testis tissues after oral administration in despite of the low absolute bioavailability, which provided the material basis for MitoQ in the treatment of testicular damage. More importantly, MitoQ reached mitochondria quickly and had an outstanding feature of mitochondria targeting in Sertoli cells. Therefore, these results provide information for the application of MitoQ against testicular injury diseases.

Venlafaxine and carvedilol ameliorate testicular impairment and disrupted spermatogenesis in rheumatoid arthritis by targeting AMPK/ERK and PI3K/AKT/mTOR pathways.

Testicular impairment has been commonly described in long-standing rheumatoid arthritis (RA) patients. Since depression and cardiovascular disorders are the most disturbing co-morbidities of RA, investigating the efficacy of the anti-depressant venlafaxine or the beta-blocker carvedilol in RA-associated testicular dysfunction may add to their clinical utility for RA patients. Previously, both agents have demonstrated significant in vivo anti-oxidant and anti-inflammatory actions. In the current study, venlafaxine (50 mg/kg/day) and carvedilol (10 mg/kg/day) were orally administered to adjuvant arthritic rats for 20 days. Interestingly, venlafaxine and carvedilol effectively suppressed paw edema and mitigated the testicular histopathological aberrations and the disrupted spermatogenesis. Both drugs enhanced testicular steroidogenesis through upregulation of 3ß-HSD, 17ß-HSD and StAR gene expression with concomitant augmentation of serum testosterone. They also blunted the inflammatory burden via attenuation of myeloperoxidase, TNF-α and the protein expression of NF-κBp65 along with elevation of IL-10. They attenuated testicular oxidative perturbations via lowering lipid peroxides and nitric oxide and boosting glutathione levels. With regard to apoptosis, the two agents lowered the protein expression of caspase-3, cleaved caspase-3, cleaved PARP, Bax and p53, promoting germ cell survival. They also modulated the AMPK/ERK signaling via lowering of p-AMPK and upregulation of p-ERK1/2 along with PI3K/AKT/mTOR transduction by enhancing the PI3Kp110α, p-AKT and p-mTOR protein expression. Together, the present work demonstrates the beneficial effects of venlafaxine and carvedilol in RA testicular dysfunction and impaired spermatogenesis via modulation of AMPK/ERK and PI3K/AKT/mTOR signaling and intervention with the testicular oxidative stress, inflammation and apoptosis.

Features of the metabolic syndrome in late adolescence are associated with impaired testicular function at 20 years of age.

STUDY QUESTION: Are early signs of metabolic disorder in late adolescence associated with features of impaired testicular function many years before the majority seek parenthood? SUMMARY ANSWER: Adolescents with features of metabolic disorder at 17 years, or insulin resistance (IR) at 20 years of age, show impaired testicular function and altered hormone levels compared to those without metabolic disorder. WHAT IS KNOWN ALREADY: Controversial evidence suggests a recent decline in sperm production potentially linked to environmental influences, but its cause remains unclear. Concomitant increases in obesity and diabetes suggest that lifestyle factors may contribute to this decline in testicular function. Although obesity has been associated with adverse testicular function in some studies, it remains unclear whether poor testicular function merely reflects, or causes, poor metabolic health. If metabolic disorder were present in adolescence, prior to the onset of obesity, this may suggest that metabolic disorder maybe a precursor of impaired testicular function. STUDY DESIGN, SIZE, DURATION: The Western Australian Pregnancy Cohort (Raine) Study is a longitudinal study of children born in 1989-1991 who have undergone detailed physical assessments since birth (1454 male infants born). At 17 years of age, 490 boys underwent a hepatic ultrasound examination, serum cytokine assessment (n = 520) and a metabolic assessment (n = 544). A further metabolic assessment was performed at 20 years (n = 608). Testicular assessment was performed at 20 years; 609 had reproductive hormones measured, 404 underwent a testicular ultrasound and 365 produced a semen sample. PARTICIPANTS/MATERIALS, SETTING, METHODS: Testicular volume was estimated by ultrasonography, and semen analysis was performed according to World Health Organization guidelines. Concentrations of LH, FSH and inhibin B (inhB) in serum were measured by immunoassay and total testosterone by liquid chromatography-mass spectrometry.At 17 years of age, a liver ultrasound examination was performed to determine the presence of non-alcoholic fatty liver disease (NAFLD), and serum analysed for the cytokines interleukin-18 and soluble tumour necrosis factor receptor 1 and 2 (sTNFR1, sTNFR2).At 17 and 20 years of age, fasting blood samples were analysed for serum liver enzymes, insulin, glucose, triglycerides (TG), total cholesterol, high density lipoprotein and low density lipoprotein cholesterol, high sensitivity C-reactive protein and uric acid. The homoeostatic model assessment (HOMA) was calculated and approximated IR was defined by a HOMA >4. Anthropometric data was collected and dual energy X-ray absorptiometry measurement performed for lean and total fat mass. As at this young age the prevalence of metabolic syndrome was expected to be low, a two-step cluster analysis was used using waist circumference, TGs, insulin, and systolic blood pressure to derive a distinct high-risk group with features consistent with the metabolic syndrome and increased cardiometabolic risk. MAIN RESULTS AND THE ROLE OF CHANCE: Men at age 17 years with increased cardiometabolic risk had lower concentrations of serum testosterone (medians: 4.0 versus 4.9 ng/mL) and inhB (193.2 versus 221.9 pg/mL) (P < 0.001 for both) compared to those within the low risk metabolic cluster. Men with ultrasound evidence of NAFLD (n = 45, 9.8%) had reduced total sperm output (medians: 68.0 versus 126.00 million, P = 0.044), testosterone (4.0 versus 4.7 ng/mL, P = 0.005) and inhB (209.1 versus 218.4 pg/mL, P = 0.032) compared to men without NAFLD.Men with higher concentrations of sTNFR1 at 17 years of age had a lower sperm output and serum concentration of inhB, with an increase in LH and FSH (all P < 0.05 after adjustment for age, BMI, abstinence and a history of cryptorchidism, varicocele, cigarette smoking, alcohol and drug use), compared to those without an elevated sTNFR1. Multivariable regression analysis, adjusting for confounders, demonstrated that men in the high-risk metabolic cluster at 20 years had a lower serum testosterone and inhB (P = 0.003 and P = 0.001, respectively). A HOMA-IR > 4 was associated with a lower serum testosterone (P = <0.001) and inhB (P = 0.010) and an increase in serum FSH (P = 0.015). LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size and multiple comparisons, and causality cannot be proven from an observational study. Due to a 3-year interval between some metabolic assessments and assessment of testicular function, we cannot exclude the introduction of a bias into the study, as some of the participants and their testicular function will not have been fully mature at the 17-year assessment. WIDER IMPLICATIONS OF THE FINDINGS: Irrespective of a proven causation, our study findings are important in that a significant minority of the men, prior to seeking parenthood, presented co-existent features of metabolic disorder and signs of testicular impairment. Of particular note is that the presence of NAFLD at 17 years of age, although only present in a minority of men, was associated with an almost 50% reduction in sperm output at 20 years of age, and that the presence of IR at 20 years was associated with a 20% reduction in testicular volume. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Australian NHMRC (Grant Numbers 634457, 35351417 and 403981) and received support from the Raine Medical Research Foundation, The Telethon Kids Institute, University of Western Australia, Women and Infants Research Foundation, Curtin University and Edith Cowan University. D.A.D., J.E.D., N.M., L.A.A., R.-C.H., T.A.M., J.K.O., L.J.B. have nothing to declare. R.J.H. is Medical Director of Fertility Specialists of Western Australia, has equity interests in Western IVF, and has received grant support from MSD, Merck-Serono and Ferring Pharmaceuticals. RMcL has equity interests in the Monash IVF Group. R.J.N. has equity interests in FertilitySA, and has received grant support from Merck Serono and Ferring Pharmaceuticals. D.J.H. has received institutional grant funding (but no personal income) for investigator-initiated testosterone pharmacology studies from Lawley and Besins Healthcare and has provided expert testimony to anti-doping tribunals and for testosterone litigation.This abstract was awarded the Fertility Society of Australia clinical exchange award for the oral presentation at ESHRE, Barcelona, in 2018.

Phenotypic testicular abnormalities and pubertal development in boys with McCune-Albright syndrome.

Aim of this survey is to review the few available literature data on pathophysiologic and clinical aspects of pubertal development in boys with McCune-Albright syndrome (MAS). On the basis of such analysis, we concluded that:1) peripheral precocious puberty (PPP) is significantly more infrequent in boys than in girls; 2) the most common testicular abnormality at MAS presentation is macroorchidism, that may be either monolateral or bilateral; 3) macroorchidism is not always associated with clinical and biochemical evidence of PPP; 4) testicular microlothiasis is distinctly more frequent in boys with MAS than in those without MAS; 5) the available therapeutic schedules have to be adopted already at MAS presentation only in the cases with PPP.

How to Treat Chronic Idiopathic Testicular Pain? Scrotoscopy with a Novel Percutaneous Endoscopy Equipment.

BACKGROUND: Management of chronic idiopathic testicular pain may be difficult because of problems identifying the causes. We evaluated "AUTOKLAV", a novel endourological nephrolithotomy device to diagnose and treat chronic idiopathic testicular pain. METHODS: We divided 103 patients to either scrotoscopy group (SG, n = 64) or open exploration group (OEG, n = 39) between September 2014 and March 2017 at Zhongnan Hospital. Perioperative information, like operating time, length of incision, and wound infections, was carefully recorded during in hospital. Follow-up data, like pain scores improvement, satisfaction with penis appearance, and adverse event, were collected at one month postoperatively. RESULTS: Finally, both the operating time and length of incision showed better performance for SG (43.6 ± 4.7 versus 51.5 ± 9.0 min; 0.7 ± 0.2 versus 4.1 ± 0.8 cm; both P <0.01). Though the pain improvement had no significant differences between the two groups (2.92 ± 0.99 and 2.14 ± 1.02, p>0.05), SG showed obvious advantages in incidence of wound infections and satisfaction with wound/scrotum appearance (0% versus 2.9%; 96.4% versus 85.3%, both P<0.05). CONCLUSIONS: In conclusion, scrotoscopy using the novel AUTOKLAV device is feasible, has an acceptable complication rate, and can be effective and safe in men with idiopathic chronic testicular pain. Etiologically, secondary inflammatory changes caused by the complete or incomplete torsion of testicular or epididymis appendices or by the existence of stones in the tunica sac might be responsible for the pain.

[Hormone Replacement Therapy in Males]. / Hormonersatztherapie des Mannes.

Testosterone is a natural hormone which is essential to maintain physical and emotional wellbeing in men. Male hypogonadism is an endocrine condition of testosterone deficiency with the potential to cause multiple morbidities and psychosocial complaints. The condition can be of primary (testicular), secondary (hypothalamic-pituitary) or so-called functional origin (as a result of inflammatory conditions, obesity or chronic illness). Testosterone deficiency can cause symptoms of sexual nature, insulin resistance, osteoporosis, anemia among others. A replacement of testosterone should not be initiated in case of desired paternity, unclear processes of the prostate, mammary gland, or high hematocrit. Diagnosis and treatment as well as surveillance of the therapy of hypogonadism are clearly regulated by international guidelines and replacement therapy is proven to be effective to ameliorate the above-named complaints when performed according to these guidelines.

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Comparison of superb micro-vascular imaging (SMI) and conventional Doppler imaging techniques for evaluating testicular blood flow.

PURPOSE: Superb micro-vascular imaging (SMI) is a new blood flow (BF) technique recently developed to outface the limitations of conventional Doppler imaging techniques (CDIT). SMI can observe micro-vascular BF and low-velocity BF. SMI is available in two modes as color SMI (cSMI) and monochrome SMI (mSMI). To evaluate testicular BF, we have compared color Doppler (CD), power Doppler (PD), cSMI, and mSMI techniques. PATIENTS AND METHODS: A total of 156 patients (310 testes) were included in the study. We evaluated BF in the testes via CD, PD, cSMI, and mSMI techniques in a heterogenous patient group. Doppler examination was performed by observing the whole testis parenchyma within the examination area at the testicular hilus level at all examinations. Spot and linear flow color encoding determined in testis parenchyma were separately counted for every examination. RESULTS: SMI was found to be superior in all age groups and testis volumes for showing the BF. When we sequenced the examinations to show the BF in testis according to their priorities, it was found that mSMI > cSMI > PD > CD. As the testis volume decreases, a significant increase is observed in mSMI when compared to other examinations in showing vascularity in pediatric age groups, in cases diagnosed with undescended testis, and in cases that underwent surgery for undescended testis. CONCLUSIONS: SMI renders more detailed vascular information on BF in the testes than CDIT. In particular, as the testis volume decreases, the priority of SMI showing BF increases. SMI should be a part of vascular examination in pediatric patients with small testis volume.

Targeted Robotic Assisted Microsurgical Denervation of the Spermatic Cord for the Treatment of Chronic Orchialgia or Groin Pain: A Single Center, Large Series Review.

PURPOSE: Microsurgical denervation of the spermatic cord is a treatment option for chronic orchialgia refractory to conservative treatment. A recent study showed specific nerve fibers as the possible cause of chronic orchialgia. Our goal was to present the outcomes of ligation of these nerves using a technique of targeted robotic assisted microsurgical denervation of the spermatic cord. MATERIALS AND METHODS: We retrospectively reviewed the records of 772 patients who underwent targeted robotic assisted microsurgical denervation of the spermatic cord from October 2007 to July 2016. Selection criteria were chronic testicular pain more than 3 months in duration, failed conservative treatments, negative neurological and urological workup, and temporary resolution of pain with a local anesthetic spermatic cord block. Targeted robotic assisted microsurgical denervation of the spermatic cord was performed. Pain was assessed preoperatively and postoperatively using a subjective visual analog scale and objectively with the standardized and validated PIQ-6 (Pain Impact Questionnaire-6) score. RESULTS: Followup data were available on 860 cases. During a median followup of 24 months (range 1 to 70) 718 cases (83%) showed a significant reduction in pain and 142 (17%) had no change in pain by subjective visual analog scale scoring. Of cases with a significant reduction in pain 426 (49%) had complete resolution and 292 (34%) had a 50% or greater reduction. Objective PIQ-6 analysis showed a significant reduction in pain in 67% of patients 6 months postoperatively, in 68% at 1 year, in 77% at 2 years, in 86% at 3 years and in 83% at 4 years. CONCLUSIONS: Targeted robotic assisted microsurgical denervation of the spermatic cord is an effective, minimally invasive approach with potential long-term durability in patients with refractory chronic orchialgia.