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Diabetes mellitus (DM) is a global health burden, affecting about 463 million of the adult population worldwide. Approximately 94% of diabetic male individuals develop varying degrees of testicular disorders (TDs), which usually result in hypogonadism, hypotestosteronemia and defective spermatogenesis and steroidogenesis. Short chain fatty acids (SCFAs) have shown potential benefits in metabolic health. However, its effect on TD associated with DM is not clear. Howbeit, the present study investigated the hypothesis that SCFAs, acetate would ameliorate TD accompanying DM, possibly by suppressing proprotein convertase subtilisin/kexin type 9 (PCSK9). Male Wistar rats (210–240 g) were allotted into groups (n = 6/group): control (vehicle; po), DM with/without 200 mg/kg (po) of sodium acetate (SAc). Diabetes was induced by streptozotocin 65 mg/kg (iv) after a dose of nicotinamide (110 mg/kg). Semen/biochemical and histological analyses were performed with appropriate methods. In addition to hyperglycemia, hyperinsulinemia and reduced insulin sensitivity, DM led to increased serum and testicular triglyceride or total cholesterol/high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, malondialdehyde, TNF-α, IL-6 and PCSK9 as well as reduced high-density lipoprotein cholesterol and glutathione. Moreover, DM caused TD which is characterized by altered sperm parameters, disrupted tissue architecture, atrophied seminiferous tubules, deleterious spermatogonia, disappearance of lumen and cellular degeneration as well as decreased luteinizing hormone and testosterone. However, the administration of SAc attenuated these alterations. The study demonstrates that DM-induced TD is accompanied by elevated PCSK9. The results however suggest that SAc rescues testicular disorder/dysfunction associated with DM by suppression of PCSK9 and improvement of insulin sensitivity.

ContextMale 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 AcquisitionThe 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/ResultsSpermatogenesis 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.ConclusionsMale 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.

Male Breast Carcinoma (MBC) is a rare condition accounting for risk factor includes hormonal imbalance, Klinefelter syndrome, testicular disorders, radiation exposure, alcoholism and antiandrogenic medication. MBC clinically manifests as painless palpable mass sometimes masquerading gynecomastia. Compared with female breast cancer, male breast carcinoma presents slightly older age at diagnosis with large tumor size and most of the tumors hormone receptor positive. We come across chronic alcoholic male presented with fungating growth over left breast. Cytology revealed neuroendocrine type of infiltrating ductal carcinoma cells, whereas biopsy showed various histological patterns in sections from different areas making this case interesting one. Immunohistochemically, it was positive for estrogen and progesterone receptor but negative for Her2neu marker. Keywords: Male Breast Carcinoma, Comedocarcinoma, Neuroendocrine, Cribriform, Schirrous, Mucinous.

Cisplatin is widely used as one of the most effective anticancer agents in the treatment of some neoplasms. Reproductive toxicity is the most common outcome associated with cisplatin testicular damage. Alternative natural medicines for treating male testicular disorders and infertility have received extensive attention in research. Natural products, medicinal herbs, and their secondary metabolites have been shown as promising agents in the management of testicular damage induced by chemotherapy drugs. This study aimed to review the research related to natural substances that are promising in mitigation of the cisplatin-induced toxicity in the reproductive system. PubMed and Scopus were searched for studies on various natural products for their potential protective property against reproductive toxicity induced by cisplatin from 2000 to 2020. Eligibility was checked based on selection criteria. Fifty-nine articles were included in this review. Mainly in animal studies, several natural agents have positively affected cisplatin-reproductive-toxicity factors, including reactive oxygen species, inflammatory mediators, DNA damage, and activation of the mitochondrial apoptotic pathway. Most of the natural agents were investigated in short-term duration and high doses of cisplatin exposure, considering their antioxidant activity against oxidative stress. Considering antioxidant properties, various natural products might be effective for the management of cisplatin reproductive toxicity. However, long-term recovery of spermatogenesis and management of low-dose-cisplatin toxicity should be considered as well as the bioavailability of these agents before and after treatment with cisplatin without affecting its anticancer activity.

The testicular disorder of sex development (TDSD) is a rare condition characterized by a male appearance with a female karyotype. The most frequent cause of TDSD is misplacement of the sex determining region Y (SRY) gene on the X chromosome. Here, we report the generation of an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a patient with SRY-positive 46,XX TDSD. This cell line offers an unprecedented cellular model to investigate the profound manifestations like infertility of the male sex reversal patients, and serves as a useful tool to develop therapies for the disease.

En la mayoría de los casos, la diferenciación sexual masculina ocurre con la participación del gen SRY. Sin embargo, se pueden presentar otros genotipos excepcionales, como en el caso que se presenta en este reporte.Se trata de un paciente adulto de sexo masculino atendido en el Servicio de Paternidades del Instituto de Genética de la Universidad Nacional de Colombia. Se le hicieron los análisis del gen de la amelogenina y de repeticiones cortas en tándem (Short Tandem Repeat, STR) específicas para el gen SRY con estuches comerciales de identificación humana, así como los de cariotipo convencional e hibridación in situ fluorescente del SRY, y el estudio de microdeleciones del cromosoma Y mediante reacción en cadena de la polimerasa (PCR). Se le hizo la evaluación clínica y se le brindó asesoramiento genético.El paciente no presentaba ambigüedad genital, su cariotipo era 46 XX, y el perfil molecular era negativo para el gen SRY y positivo para el ZFY. Se le diagnosticó un trastorno de diferenciación sexual 46 XX testicular no sindrómico, una rara condición genética. Solo el 20 % de los pacientes con este diagnóstico son negativos para SRY y exhiben perfiles moleculares diversos. La información disponible parece indicar que el ZFY está relacionado con la diferenciación sexual masculina, aún en ausencia del gen SRY.

Health outcomes among men are poorer than women and little efforts have been made by health organizations to promote men’s health. Testicular disorders can have a negative effect on men’s health and are rarely addressed in pre-existing men’s health policies. Findings from the empirical literature on men’s awareness of testicular disorders suggest that men’s knowledge of testicular disorders is lacking and their intentions to seek timely medical attention for testicular symptoms are low. This paper aims to introduce the concept of ‘testicular awareness’ and explore its implications for health research, practice, and education. The key attributes of ‘testicular awareness’ include: (i) familiarity with own testes; (ii) knowing what is normal versus abnormal; (iii) ability to detect an abnormality; and (iv) knowing own risk factors. Testicular awareness is an all-encompassing concept since it helps men become familiar with a body part that is seldom discussed and enables them to detect testicular abnormalities and to seek timely medical attentions for testicular symptoms, regardless of the ultimate diagnosis. Testicular awareness can be promoted using a number of strategies; these include but are not limited to: (i) involving men in drafting men’s health policies that address testicular awareness; (ii) partnering with men to develop and test interventions promoting testicular awareness; (iii) being cognizant of the learning needs of men who are at risk of health disparities including those with low literacy and health literacy; (iv) promoting testicular awareness in clinical practice and health education; and (v) using men’s daily spheres of information (e.g. workplaces, universities, gyms, and community organizations) to promote testicular awareness.

SRY-negative 46,XX testicular disorders of sex development (DSD) are very rare conditions. Recently, we identified a novel heterozygous NR5A1 mutation, p.Arg92Trp (c.274C>T, p.R92W), in 2 unrelated cases of 46,XX testicular/ovotesticular DSD. We report the clinical course from infancy to puberty in a Japanese male with SRY-negative 46,XX testicular DSD, carrying this p.Arg92Trp mutation in NR5A1. The patient naturally acquired the development of a penis and pubic hair during puberty. However, hypergonadotropic hypogonadism subsequently developed. More clinical cases will be needed to fully understand the effects of the p.Arg92Trp mutation on the ability to maintain testosterone secretion in 46,XX testicular DSD.

The purpose of this paper was to analyse the aetiology and methods of diagnosing reproductive disorders in male dromedary camels. Male camel infertility manifests as one of three conditions: post-coital infertility (IG), inability to copulate (IC) and lack of sexual desire (LSD). IG is mainly a testicular disorder that is linked to a deteriorated seminogram, arrested spermatogenesis, Sertoli cell-only syndrome and testicular degeneration. For IG diagnosis, semen analysis, testicular biopsy and fine-needle aspiration are gold standards. Testicular ultrasonography was generally inefficient. High serum FSH was found in IG camels with oligo- and azoospermia, implying primary spermatogenesis defects. The testis-expressed protein (TEX101) and the epididymis-expressed protein (ECM1) are reliable biomarkers for distinguishing between obstructive and non-obstructive azoospermia. IC manifests in two forms: phimosis (PHI) and erectile dysfunction (ED). PHI is frequently linked to preputial and penile pathologies, as well as leucocytosis, neutrophilia and elevated nitric oxide metabolites. The majority of camels with ED have normal genital organs, and the condition is associated with an increase in cardiac troponin I. LSD is a rare disorder brought on by hormonal imbalances, high temperatures, stress and debilitating diseases. In conclusion, IG diagnosis necessitates semen analysis, testicular biopsy or fine-needle aspiration, and FSH testing, whereas IC diagnosis requires preputial and penile examinations. Diagnostic aids include serum and seminal biomarkers.

Acquired testicular disorders are a spectrum of disease characterized by the presence of testicular damage that may recognize traumatic etiology or, less frequently, may be due to environmental pollutants or drug adverse reactions, i.e., antiandrogens or corticosteroids. Even if traumatic disorders may often affect young adolescents, they are rather frequent also in adult life, while post-infective disease is more frequent in adult and elderly men. Recognizing clinical signs, diagnosis, and treatment options is important for clinicians to prevent infertility and associated sexual disturbances in most cases. This chapter will discuss most important features for diagnosing acquired testicular disease and its treatment.

The risk of a gonadal tumor is high in testicular disorder of sexual development (DSD) with the Y chromosome, but cases of DSD without the Y chromosome are extremely rare. We reported a gonadal tumor in a phenotypically male individual with 46, XX testicular DSD. A testicular tumor was incidentally found in a 32-year-old phenotypic male who was presented to the hospital with male infertility. A diagnosis of 46, XX testicular DSD was made by the presentation of karyotype analysis of 46, XX with the sex-determining region of the Y chromosome (SRY) positive and gonadal tissue without female gonads. Surgery was performed due to a gradually growing tumor. The partial orchidectomy was performed with the diagnosis of a benign Leydig cell tumor in frozen biopsy.

The follicle-stimulating hormone receptor (FSH-R) expression was always considered human gonad-specific. The receptor has also been newly detected in extragonadal tissues. In this finding, we evaluated FSH-R expression in the human male early genital tract, in testicular tumors, and in sperm from healthy and varicocele patients. In sperm, we also studied the mechanism of FSH-R action. Immunohystochemistry and Western blot analysis showed FSH-R presence in the first pathways of the human genital tract, in embryonal carcinoma, and in sperm, but it was absent in seminoma and in lower varicocele. In sperm, FSH/FSH-R activity is mediated by G proteins activating the PKA pathway, as we observed by using the H89. It emerged that increasing FSH treatments induced motility, survival, capacitation, and acrosome reaction in both sperm samples. The different FSH-R expression in tumor testicular tissues may be discriminate by tumor histological type. In spermatozoa, FSH-R indicates a direct action of FSH in these cells, which could be beneficial during semen preparation for in vitro fertilization procedures. For instance, FSH positive effects could be relevant in idiopathic infertility and in the clinic surgery of varicocele. In conclusion, FSH-R expression may be considered a molecular marker of testicular disorders.

Testicular cancer is the most common cancer among men younger than 50, and benign testicular disorders such as torsion and epididymitis can be life-threatening if left untreated. Men’s awareness of testicular disorders is lacking, and their intentions to see help for symptoms of testicular disease are low. This study aimed to describe the development, feasibility, and usability of a virtual reality (VR) intervention designed to enhance men’s awareness of testicular disorders (E-MAT). We designed E-MAT as a three-level VR experience and tested its feasibility and usability with 15 men recruited from a university. Following exposure to the intervention, participants filled a 43-item questionnaire. Participants agreed that the technology was comfortable to use, testicular disorders were well represented, the use of light humor was appropriate, and the scientific facts were easy to understand. Participants also agreed that the intervention was suited for men from different sociodemographic backgrounds and felt confident using VR. Overall, participants perceived the intervention as user-friendly, enjoyable, and aesthetically appealing. To the best of our knowledge, VR has not been used to promote men’s health in the past, let alone increasing their awareness and help seeking for testicular disorders. We recommend testing the effectiveness of E-MAT and making it available on public platforms that men can access at their own leisure. VR can be used in future interventions to educate men about various health topics.

Aims As nitric oxide (NO) production is essential for insulin signaling, glucose uptake, endothelial function, and regulation of apoptosis, the loss of bioavailable NO may be a mechanism underlying the development of diabetes complication. Dietary nitrate acts as a substrate for NO generation, thus serving as a physiological source of NO. This study evaluated the therapeutic effects of nitrate supplementation on the apoptosis-induced testicular disorders in diabetic rats. Main methods Fifty male Wistar rats were divided into five groups; control, control with 100 mg/L nitrate in distilled drinking water, diabetes, diabetes treated with 2–4 U/day NPH insulin, diabetes treated with 100 mg/L nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and epididymis were collected to assess the apoptosis process and the stereology of testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose, insulin, and NOx levels were investigated. Key findings The results of this study indicated that nitrate treatment ameliorated the sperm parameters, testicular morphometrical and stereological alterations, reduced blood glucose, the number of TUNEL positive cells and tubules, and testicular expressions of p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and NOx levels, and testicular expression of miR-449a in streptozotocin-induced diabetic rats. Significance Our in vivo evidence revealed that nitrate treatment may has a favorable effect as an exogenous NO donor on experimental diabetic testicular damages in which NO bioavailability is impaired.

Testicular tumours are the most common neoplasms in male dogs accounting for approximately 90% of all tumours affecting the genitourinary tract. Gray-scale ultrasonography in combination with colour and power Doppler imaging has been well accepted as an accurate technique for assessing scrotal lesions and vascularization of the testis. Colour Doppler sensitivity for low blood flows appears promising in the study of testicular disorders. The aim of this study was to assess if colour and power Doppler ultrasound is a good tool for the investigation of testicular lesions in dogs, to report the sonographic features of lesions and to measure colour and power Doppler parameters such as resistive index (RI), pulsatility index (PI), hypovascularization and hypervascularization (VI) determining if they can be used to distinguish testicular neoplasms from the wide spectrum of non-neoplastic pathological findings. In this study, 50 male dogs of various breeds, aged between 7 and 14 years, presented with testicular disorders were selected. RI and PI were calculated. Mean RI values for neoplastic, inflammatory and degenerative lesions were 0.54, 0.45 and 0.58, respectively. Mean PI values were 0.62, 0.55 and 0.63, respectively. Hypovascularization and hypervascularization of the lesion were evaluated throughout the vascularity index (VI). Vascular signals in neoplasms were significantly intensified around and inside the mass if compared with those measured during inflammatory and degenerative lesions. VI markedly increased in solid tumours. Pathological testes were removed; macroscopical, histological and immunoistochemical evaluations were carried out. Colour Doppler showed increased intralesional and peripheral flows in all neoplastic lesions analysed. No flows were detected around cysts.

Background The incidence of benign and malignant testicular disorders is on the rise. Three literature reviews and one qualitative study found that men’s awareness of testicular disorders was lacking, and their intentions to seek help for symptoms of testicular disease were low. Objectives The aim of the study was to enhance men’s awareness of testicular disorders, help-seeking intentions for testicular symptoms, and intention and behavior to feel their testes. Methods Men aged 18–50 years were recruited from a university and asked to engage in a three-level, educational, virtual reality experience. The Medical Research Council framework guided the development and pilot testing of the intervention. Knowledge, awareness, perceived risk, implementation intentions, help-seeking intentions, and behaviors were measured at pretest (T0), immediately posttest (T1), and 1 month posttest (T2). Results Data were available from 49 participants. In comparison to T0, a significant increase in knowledge (mean difference [ MD ] = 3.5, 95% CI [2.8, 4.26]); testicular awareness ( MD = 0.2, 95% CI [0.01, 0.41]); implementation intentions ( MD = 0.6, 95% CI [0.33, 0.90]); and help-seeking intentions for testicular swelling ( MD = 0.3, 95% CI [0.12, 0.51]), lumpiness ( MD = 0.3, 95% CI [0.08, 0.46]), and pain ( MD = 0.6, 95% CI [0.25, 1.01]) was noted at T1. This increase was maintained at T2. Participants who expressed an intention to feel their testes at T0 were more likely to report performing this behavior at T2. Discussion The intervention succeeded in promoting knowledge, testicular awareness, implementation intentions, help-seeking intentions, and behaviors. A randomized controlled trial of the Enhancing Men’s Awareness of Testicular Disorders intervention with a larger sample size is warranted.

Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal (MIM # 610644) is a clinically distinctive form of SRY-negative 46,XX disorder of sex development. It is a rare autosomal recessive disorder caused due to biallelic loss of function mutations in RSPO1 gene. RSPO1 acts by activating the canonical β-catenin pathway and is one of the most important genes controlling female gonadal differentiation. RSPO1-associated disorders of sex development have been described only in three instances in the past. We report fourth such case with additional findings and perform a comparative review of previous phenotypic descriptions, thereby expanding the clinical phenotype of this syndrome.

Background: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion. Methods: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method. Results: ICC was 0.915 [95% confidence interval (CI): 0.828–0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method. Conclusions: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

Testicular XX disorder of sex development (XX DSD, SRY -negative), causing sterility, is quite frequently diagnosed in pig populations, however, its molecular background is still unknown. This disorder may affect carcass quality (boar taint) due to the presence of testicular tissue in animals with ambiguous female external genitalia. A chromosome fragment encompassing the SOX9 gene was previously considered as a candidate region in functional and association studies. We analyzed distribution of polymorphic variants in 5’UTR and in 3’-flanking regions of the SOX9 gene in a cohort of 12 XX DSD pigs and a panel of 116 normal females. Altogether, 8 previously known polymorphic sites were analyzed and no significant association under Bonferroni correction (P>0.0063) between DSD phenotype and identified SNPs was found. The region harboring the SOX9 gene was also searched for the presence of copy number variation (CNV) by fluorescence in situ hybridization technique (FISH), using a set of 7 BAC probes. A potential CNV region, manifested by size variation (large and small) of fluorescence signals, produced by a single BAC probe hybridizing downstream (approx. 500 kb) of the SOX9 gene, was observed in 4 DSD cases. We conclude, that a new CNV polymorphism in the region harboring SOX9 gene can be considered as a promising marker for the DSD phenotype.

Purpose: We aimed to identify the genetic cause in a cohort of 11 unrelated cases and two sisters with 46,XX SRY-negative (ovo)testicular disorders of sex development (DSD). Methods: Whole-exome sequencing (n = 9), targeted resequencing (n = 4), and haplotyping were performed. Immunohistochemistry of sex-specific markers was performed on patients' gonads. The consequences of mutation were investigated using luciferase assays, localization studies, and RNA-seq. Results: We identified a novel heterozygous NR5A1 mutation, c.274C>T p.(Arg92Trp), in three unrelated patients. The Arg92 residue is highly conserved and located in the Ftz-F1 region, probably involved in DNA-binding specificity and stability. There were no consistent changes in transcriptional activation or subcellular localization. Transcriptomics in patient-derived lymphocytes showed upregulation of MAMLD1, a direct NR5A1 target previously associated with 46,XY DSD. In gonads of affected individuals, ovarian FOXL2 and testicular SRY-independent SOX9 expression observed. Conclusions: We propose NR5A1, previously associated with 46,XY DSD and 46,XX primary ovarian insufficiency, as a novel gene for 46,XX (ovo)testicular DSD. We hypothesize that p.(Arg92Trp) results in decreased inhibition of the male developmental pathway through downregulation of female antitestis genes, thereby tipping the balance toward testicular differentiation in 46,XX individuals. In conclusion, our study supports a role for NR5A1 in testis differentiation in the XX gonad. Genet Med 19 4, 367–376.

Ovotesticular or testicular disorder of sexual development in dogs with female karyotype and lack of SRY (XX DSD) is a common sexual anomaly diagnosed in numerous breeds. The molecular background, however, remains unclear, and epigenetic mechanisms, including DNA methylation, have not been studied. The aim of our study was comparative methylation analysis of CpG islands in promoters of candidate genes for XX DSD: SOX9, SOX3, and WNT4. Methylation studies were performed on DNA extracted from formalin-fixed/paraffin-embedded or frozen gonads from 2 dogs with ovotesticular and 2 dogs with testicular XX DSD as well as control females (n = 4) and males (n = 2). Bisulfite-converted DNA was used for CpG methylation analysis using quantitative pyrosequencing. Promoter regions of SOX9 and WNT4 showed similar CpG methylation in each group, ranging from 0 to 5.5% and from 39 to 74%, respectively. The SOX3 promoter showed significantly higher methylation in the ovotesticular XX DSD cases and the testicular XX DSD and control males, suggesting that SOX3 methylation may play a role in canine XX DSD pathogenesis.

Made available in DSpace on 2019-10-06T16:26:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Cryptorchidism (CPT), the most common male congenital abnormality, is variably associated with other male reproductive tract problems. We evaluated if cryptorchid rats develop enhanced testicular susceptibility to dibutyl phthalate (DBP) or acrylamide (AA) after extended exposure. Three studies with rats were performed: (1) in utero and postnatal exposure to DBP or AA; (2) establishment of CPT and orchiopexy; and (3) in utero and postnatal exposures to DBP or AA associated with CPT/orchiopexy. Seminiferous tubules were histologically scored according to the severity of lesions: (1) Rats exposed to DBP (score 1.5) or AA (score 1.1) presented mostly preserved spermatogenesis. Some seminiferous tubules showed vacuolated germinative epithelium, germ cell apoptosis, and a Sertoli cell-only (SCO) pattern. (2) CPT (score 3.3) resulted in decreased absolute testes weights, degenerated and SCO tubules, and spermatogenesis arrest that were reversed by orchiopexy (score 1.1). (3) Exposure to DBP or AA with CPT/orchiopexy led to atrophic testes, spermatogenesis arrest, germ cell exfoliation/multinucleation, and SCO tubules (both chemicals score 2.5). Exposure to chemicals such as DBP or AA prevented the recovery of cryptorchid testes by orchiopexy. The possible role of environmental contaminants should be considered when looking for factors that modulate human testicular disorders associated with CPT. Department of Pathology Center for Evaluation of the Impact of the Environmental on Human Health (TOXICAM) Botucatu Medical School Botucatu Campus Sao Paulo State University (UNESP) Department of Physiology Polytechnic Centre Federal University of Paraná Department of Pathology and Microbiology and the Fred and Pamela Buffett Cancer Center University of Nebraska Medical Center Havlik-Wall Professor of Oncology University of Nebraska Medical Center Department of Pathology Center for Evaluation of the Impact of the Environmental on Human Health (TOXICAM) Botucatu Medical School Botucatu Campus Sao Paulo State University (UNESP) CNPq: 132667/2013-4

Disorders of sexual development (DSD) in wild mammals are rarely described. A male South African giraffe (Giraffa camelopardalis giraffa) was identified with bilateral cryptorchidism. The testes were intra-abdominal, smaller and less ovoid than in normal male giraffes. The right testis was situated more cranially than the left and connected to a longer deferent duct with normal ampullae. One distended vesicular gland filled with mucoid material was identified. A short penis, situated in the perineal area, was directed caudally and presented hypospadias. Histologically, testicular hypoplasia was present; the epididymis tubules contained no spermatozoa and the deferent duct and vesicular gland were inflamed. The blood testosterone concentration was 16.27 nmol/L and oestrone sulphate concentration was 0.03 ng/mL. The aetiology of the abnormalities is unknown.

Rationale Chromosome karyotype analysis and SRY (sex determined region of Y chromosome) gene detection are routines for the diagnosis of growth hormone deficiency (GHD), but further whole exome gene sequencing occasionally leads to subversive results and unexpected conclusions. Patient concerns We report a single case of a 7-year-old Chinese boy who had stunted growth since he was 1 year old. He was short in height (height Standard Deviation Score (SDS) was less than 2.9), bilateral scrotal dysplasia and delayed bone age. Diagnosis His growth hormone (GH) stimulation tests showed GHD. His karyotype analysis and polymerase chain reaction (PCR) analyses indicated a 46, XX disorder of sex development (DSD) without the presence of the SRY gene. Nevertheless, considering that female gonad was not observed in the chest and abdominal magnetic resonance imaging, the whole exome gene sequencing was performed. Sequencing data confirmed the presence of SRY gene sequence and two copies of chromosome X. Later, using different primer sequences for PCR, it showed that the SRY gene was positive. The final diagnosis was a rare case of "46, XX (SRY positive) testicular DSD with GHD". Interventions The boy's parents agreed to use recombinant human growth hormone (rhGH) for GHD treatment, the starting dose was 0.035 mg / kg / day. But they disagreed with molecular diagnostics and genomic analysis of the Y chromosome. Outcomes The boy was treated with rhGH for 3 months and his height increased by 2.2 cm. The patient will be followed-up until the end of his puberty. Lessons In summary, whole exome gene sequencing overturned the preliminary diagnosis results of karyotype analysis and SRY gene detection, and found that there may be a certain correlation between testicular DSD and GHD.

Virilisation of the XX foetus is the result of androgen excess, resulting most frequently from congenital adrenal hyperplasia in individuals with typical ovarian differentiation. In rare cases, 46,XX gonads may differentiate into testes, a condition known as 46,XX testicular disorders of sex development (DSD), or give rise to the coexistence of ovarian and testicular tissue, a condition known as 46,XX ovotesticular DSD. Testicular tissue differentiation may be due to the translocation of SRY to the X chromosome or an autosome. In the absence of SRY, overexpression of other pro-testis genes, e.g. SOX family genes, or failure of pro-ovarian/anti-testis genes, such as WNT4 and RSPO1, may underlie the development of testicular tissue. Recent experimental and clinical evidence giving insight into SRY-negative 46,XX testicular or ovotesticular DSD is discussed.

Testicular or ovotesticular disorder of sex development (DSD) in genetic females (78,XX; SRY-negative) has been reported quite frequently in numerous dog breeds and is usually diagnosed due to the presence of female external genitalia with an enlarged clitoris. The molecular background of this disorder, diagnosed also in human and other mammals, is not fully understood. However, it has recently been proposed that a copy number variation (CNV) in the region upstream of the SOX9 gene is associated with it. We described a rare case of this disorder in a French Bulldog with abdominal testes and male external genitalia (a slightly malformed penis). FISH studies showed a female karyotype, lack of a translocation involving the Y chromosome, and a distinct size variation in the CNV region (CNVR) upstream of the SOX9 gene, located on chromosome 9 (CFA9). A large FISH variant on a single CFA9 and a lack of the variant on its homologue was observed. Surprisingly, in the mother of this DSD dog, 2 normal-sized variants were identified which means that the CNV in the DSD dog was de novo. Our observations are in agreement with earlier suggestions that a high number of copies at the CNVR upstream of SOX9 may be associated with this type of DSD.

A custom CGH microarray that covers the SOX9 regulatory region. Log2 ratio scatterplot showing individual data points. Blue box highlights copy number gain with 3' breakpoint region magnified.

Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD.

Men Breast Cancer (MBC) is uncommon and occurs after the age of 60 years. Among men Prognosis is poor as Prognosis a course of a medical condition is discovered at a late stage. where Infiltrating ductal carcinoma accounts for (70-90%) of male breast cancers. In situ but not invasive carcinoma is exclusively ductal, and it accounts only 7% of the breast cancer cases in males. It is observed that 50-75% of breast cancer cases are spread to lymph nodes. The etiology of male breast cancer is unknown. An excess risk has been associated with the testicular disorders, benign breast disease including gynecomastia, Klinefelter syndrome, etc., Preliminary evidence suggests that BRCA2 is a strong cause. The carriers of the males with BRCA2 mutation have an increased lifetime risk of breast cancer with 80-fold in it. It is also known that there is also a risk of breast cancer associated with undescended testes and it is also related to orchiectomy, orchitis, testicular injury, etc., with an increasing number of children the decreasing trend in risk was observed gradually. Where It is also known that Liver cirrhosis is associated with increased levels of estrogens possibly via high levels of endogenous estrogens.

Isoniazid is reported to be the most reliable and cost-effective remedy for tuberculosis treatment and prophylaxis among first line anti-tuberculosis drugs. Conventionally, the most common and best studied adverse effect of isoniazid is hepatotoxicity, but as for testicular toxicity the problem has not yet explored extensively. The aim of the study was to identify in vivo influence of isoniazid on induction of testicular cytochrome Р-450 2Е1 (CYP2E1) mRNA expression and enzymatic activity, testes DNA fragmentation, serum total testosterone level, and spermatogenesis indices. The significant induction of CYP2E1 was demonstrated in rat’s testes following isoniazid administration, specifically CYP2E1 mRNA expression and p -nitrophenolhydroxylase activity was increased in 28 and 7 times as compared with control, respectively. These changes were accompanied by activating of testicular GST in 32%, changing in levels and character of DNA fragmentation, as well as damaging of the spermatogenic epithelium, decreasing in serum testosterone content (1.62 fold), sperm count (19%), and losing of fertility in comparison with untreated males. We assume that in testes of isoniazid-treated rats CYP2E1 may act as a trigger in generating of reactive oxygen species and other toxic metabolites which subsequently mediates DNA damage, spermatogenesis disturbances, and altered male fertilizing capacity.

Hypogonadism or Testosterone Deficiency (TD) in adult men as defined by low levels of serum testosterone accompanied by characteristic symptoms and/or signs as detailed further on can be found in long-recognized clinical entities such as Klinefelter syndrome, Kallmann syndrome, pituitary or testicular disorders, as well as in men with idiopathic, metabolic or iatrogenic conditions that result in testosterone deficiency. These recommendations do not encompass the full range of pathologies leading to hypogonadism (testosterone deficiency), but instead focus on the clinical spectrum of hypogonadism related to metabolic and idiopathic disorders that contribute to the majority of cases that occur in adult men.

Background It has been seen that despite the increasing incidence of benign testicular disorders (BTDs), little work has been done towards its awareness among the male populace. Also, the trend of not seeking help in this regard is concerning. In this study, we aim to better perceive the level of understanding and common practices regarding BTDs among educated young men. Methods A cross-sectional study was carried out among two groups of ages 14-20 and 21-28 years. The inclusion criterion was that of educated males in an urban setting. Data were collected through a standardized questionnaire using cluster sampling by independent interviewers. The questionnaire consisted of four parts dealing with demographics, knowledge, attitudes and practices. Chi-square and Mann-Whitney U test were used as the primary statistical tests. Results The sample population consisted of an equal number of participants between the ages of 14 and 20, and between 21 and 28 years (n = 200, 50%). About half the participants (n = 215, 53.8%) were not familiar with the term BTDs. The majority (n = 324, 78.8%) of participants were not aware of symptoms of BTDs. Three-fourth of the participants believed that the subject is considered taboo in Pakistan (n = 307, 73.6%) while a majority of participants (n = 340, 85%) believed media coverage can help spread awareness of BTDs. A huge number (n = 268, 67%) thought that BTDs can cause fertility problems while one-third of them would not perform testicular self-examination (TSE) in case of pain or swelling in the scrotal region (n = 119, 29.8). The level of education and age were significantly associated with the knowledge regarding symptoms and types of BTDs. Conclusion Knowledge of BTDs and practices of TSE in the young educated men of Karachi are alarmingly poor. Therefore, there is an urgent need to create awareness at all levels using different strategies and platforms.

The 46, XX male syndrome, or the 46, XX testicular Disorder of Sexual Differentiation (DSD) is rare. We report a clinical case of a male infant 46, XX, DSD with SRY negative. This observation suggests that genes other than SRY play an important role in determining sex. From this case we will present a review of the literature to take stock of the subject.

Contents An eight-month-old female dog presented with ambiguous external genitalia. A thorough clinical examination together with various imaging techniques and a histology examination showed the presence of two testicles linked to both the Mullerian and Wolffian ducts. The discovery of the 78,XX SRY-negative karyotype led to the diagnosis of incoherence between the chromosomal and gonadal sex, which is typical for a 78,XX testicular disorder of sex development. Our case was unique because the testicles were still located in their normal scrotal position, whereas the literature contains reports of the presence of cryptorchid testicles in this karyotype setting. To our knowledge, this is the first case that describes an SRY-negative 78,XX testicular disorder of sex development with bilateral scrotal testicles.

We report four patients with SRY-positive 46,XX testicular disorders of sex development (46,XX-TDSD) (cases 1-4). Case 1 exhibited underdeveloped external genitalia with hypospadias, case 2 manifested micropenis and cases 3 and 4 showed normal external genitalia. The Xp;Yp translocations occurred between the X- and the Y-differential regions in case 1, between PRKX and inverted PRKY in case 2 and between the X-chromosomal short arm pseudoautosomal region and the Y-differential regions in cases 3 and 4. The distance of the Yp breakpoint from SRY was ~0.75 Mb in case 1, ~6.5 Mb in case 2, ~2.3 Mb in case 3 and ~72 kb in case 4. The Xp;Yp translocation occurred within an 87-bp homologous segment of PRKX and PRKY in case 2, and between non-homologous regions with addition of an 18-bp sequence of unknown origin in case 4. X-inactivation analysis revealed random inactivation in cases 1-4. The results argue against the notion that undermasculinization in 46,XX-TDSD is prone to occur when translocated Yp materials are small (100 kb of the Y-differential region), and imply that the Xp;Yp translocations result from several mechanisms including non-allelic homologous recombination and non-homologous end joining.

Background: The global distribution of testicular disorders differs conforming with differences in demographic denominators. The diagnostic dictum for these disorders customarily adheres to findings at clinical assessment, relevant imaging, and laboratory evaluation. Histopathological confirmation remains the ultimate for the diagnosis of testicular malignancies and many testicular dysfunctions. The epidemiological review of the histological outcomes among Kano populace, however, is deficient. Objective: The aim of the study was to analyse histological pattern of testicular lesions in Kano, Nigeria. Methodology: The study is a 14-year retrospective review of testicular specimens subjected to histology in Kano from January 2003 to December 2016. The variables obtained were the age of patients, laterality, and histological diagnoses. These were collated and analyzed; the findings were presented as mean, patients’ age range, and laterality ratio with frequency tables. Results: Three hundred and forty-three testicular tissues were assessed. The nonneoplastic lesions were 79.2% with patients’ age range of 3–90 years. Atrophies and maturation arrests formed 29.4% and 18.0%, respectively. Specimens from the right were more with a ratio of 1.6:1. Neoplastic lesions were 3.5% and patients’ age range from 3 to 65 years. Seminomas were the predominant neoplastic lesion and constituted 66.7%. The right testes were more commonly affected and have a ratio of 1.4:1. Conclusion: This appraisal affirms that testicular lesions could be found across a wide age range and majorities are nonneoplastic. The findings in this study concur with the published African and Asian conclusions.

Testicular feminization syndrome or androgen insensitivity syndrome is a rare inherited form of male pseudohermaphroditism that occurs in phenotypically normal woman with male karyotype (XY), with an incidence of 1:20,000-64,000 male births. The individual with complete form of this syndrome have female external genitalia while those with partial form have variable ambiguity of genitalia. The undescended testis may go into malignant transformation. The androgen insensitivity syndrome with malignant testicular disorder is very rare. A twenty-eight year old female was admitted to the hospital with the complaint of primary amenorrhea. Clinical and laboratory investigation revealed testicular feminization syndrome with seminoma developed from intraabdominal undescended testis. Primary removal of the mass and postoperative chemotherapy was treatment of choice for the patient.

This study investigated oxidative stress-mediated alterations in the reproductive profile of streptozotocin-induced diabetic albino rats and their amelioration by the polyherbal formulation MTEC (modified), constituted with n-hexane fractions of hydromethanol extracts of Musa paradisiaca roots, Tamarindus indica seeds, Eugenia jambolana seeds, and Coccinia indica leaves in a specific ratio. We noted a change in serum insulin levels and a modulation in carbohydrate metabolic parameters, i.e. increased fasting blood glucose level, elevated glucose-6-phosphatase and lactate dehydrogenase activities, along with a diminution of hexokinase and glucose-6-phosphate dehydrogenase activities in liver, skeletal muscle, and cardiac muscle, which confirmed the streptozotocin-induced diabetic state. Glycogen levels were decreased in the liver and skeletal tissues. A diminution in reproductive function in the diabetic state was reflected here by significant low values in reproductive organo-somatic indices, sperm count, and motility, along with serum testosterone, but high levels of testicular cholesterol and seminal vesicular fructose. A diminution in activity of the principal antioxidative enzymes along with increased levels of free radical products in the primary and accessory sex organs, as well as in sperm pellets, also confirmed the development of oxidative stress in the male reproductive organs. An increased expression of testicular proapoptotic Bax gene in diabetes also supports the elevation of testicular germ cell apoptosis in the diabetic state. Oral administration of the herbal drug MTEC (modified) at a dose of 10 mg/0.5 mL 2% Tween 80 per 100 g body weight twice daily to the diabetic rats for 28 days significantly corrected the serum insulin level and carbohydrate metabolic parameters. MTEC (modified) also corrected reproductive activities by increasing organo-somatic indices, sperm count, motility, levels of serum testosterone, testicular cholesterol, and seminal vesicular fructose toward their respective control values. Oxidative stress-mediated testicular deformities in diabetes were rectified by treatment with MTEC (modified), as shown here by the increasing activities of antioxidative enzymes and decreasing levels of lipid peroxidative end-products, along with a downregulated pattern of proapoptotic Bax-α protein in testicular tissue, without any development of toxicity. Thus, MTEC (modified) has promising hyperglycemic, antioxidative, and antiapoptotic activities for curing diabetes-induced testicular disorders in a streptozotocin-treated diabetic rat model.

Cryptorchidism or undescended testes (UDTs) is the failure of one or both testes to descend from the pararenal embryological origin to the base of the scrotum. If uncorrected, boys with UDT are at a higher risk of infertility and malignancy (Desireddi et al., J Urol 180:1805–8, 2008; Samadi et al., J Endourol 17:365–8, 2003; Heyns CF. J Anat 153:93–112, 1987; Wenzler et al., J Urol 171:849–51, 2004). It is therefore important to identify these patients early and ensure follow-up so that orchiopexy can be performed in a timely manner if spontaneous descent does not occur. Diagnostic laparoscopy is the gold standard for the diagnosis of a non-palpable testis, and the laparoscopic approach for cryptorchidism has replaced the combined inguinal/retroperitoneal open approach.