Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

DEFF Research Database (Denmark)

Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

2014-01-01

to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

Paradoxical sleep deprivation changes testicular malondialdehyde and caspase-3 expression in male rats

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Fitranto Arjadi

2015-08-01

Full Text Available BACKGROUND Sleep deprivation is a significant problem among adult men and is considered as a risk factor for several diseases. Paradoxical sleep deprivation (PSD induces Leydig cell apoptosis through elevation of corticosterone, with testicular malondialdehyde (MDA and Leydig cell caspase-3 expression as parameters. The aim of this study was to observe testicular MDA level and caspase-3 expression treated with paradoxical sleep deprivation (PSD, immobilization, and footshock stress and to determine the stress model with a significant effect in white male rats (Rattus norvegicus . METHODS This experimental randomized study of posttest only with control group design was conducted on 24 white male Wistar strain rats, randomly allocated into four treatment groups, i.e. control (K1 without any stress treatment, PSD (KII, immobilization (KIII, and footshock stress (KIV. Treatments were given for 25 days to produce chronic stress. Testicular MDA concentration was examined by the ELISA method while caspase-3 was examined by the TUNEL method. RESULTS Mean testicular MDA concentration with one-way ANOVA test showed differences in means between the groups (p=0.000 and post hoc Tukey-HSD test showed significant results between PSD stress group versus control, immobilization and footshock stress groups. One-way ANOVA test showed a significant difference in caspase-3 expression in at least two treatment groups (p=0.008 and post-hoc Tuckey-LSD test showed significant differences between controls and all stress groups. CONCLUSION Sleep deprivation is a type of stress inducing changes in testicular MDA concentration and caspase-3 expression in male rat testes.

Pig StAR: mRNA expression and alternative splicing in testis and Leydig cells, and association analyses with testicular morphology traits.

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Zhang, Yanghai; Cui, Yang; Zhang, Xuelian; Wang, Yimin; Gao, Jiayang; Yu, Ting; Lv, Xiaoyan; Pan, Chuanying

2018-05-31

Steroidogenic acute regulatory protein (StAR), primarily expressed in Leydig cells (LCs) in the mammalian testes, is essential for testosterone biosynthesis and male fertility. However, no previous reports have explored the expression profiles, alternative splicing and genetic variations of StAR gene in pig. The aim of current study was to explore the expression profiles in different tissues and different types of testicular cells (LCs; spermatogonial stem cells, SSCs; Sertoli cells, SCs), to identify different splice variants and their expression levels, as well as to detect the indel polymorphism in pig StAR gene. Expression analysis results revealed that StAR was widely expressed in all tested tissues and the expression level in testis was significantly higher than that in other tissues (P StAR mRNA expression level was significantly higher in LCs than others (P StAR-a, StAR-b and StAR-c, were first found in pig. Further study showed StAR-a was highly expressed in both testis and LCs when compared with other variants (P StAR-a was the primary variant at StAR gene post-transcription and may facilitate the combination and transportation of cholesterol with StAR. In addition, a 5-bp duplicated deletion (NC_010457.5:g.5524-5528 delACTTG) was verified in the porcine StAR gene, which was closely related to male testicular morphology traits (P StAR gene might be a positive allele. Briefly, the current findings suggest that StAR and StAR-a play imperative roles in male fertility and the 5-bp indel can be a potential DNA marker for the marker-assisted selection in boar. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcrição reversa na determinação da expressão do mRNA para a enzima conversora de angiotensina testicular em animais tratados com zinco Assessment of the reverse transcriptase polymerase chain reaction technique in the determination of the mRNA expression for the testicular angiotensin-converting enzyme in zinc treated rats

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Gilberto Simeone Henriques

2005-12-01

Full Text Available OBJETIVO: O objetivo deste trabalho foi otimizar as condições reacionais capazes de ocasionar variabilidade e de introduzir erros sistemáticos na reação em cadeia pela polimerase aplicada à análise da expressão gênica da isoforma testicular da enzima conversora de angiotensina. MÉTODOS: Avaliaram-se a concentração de cDNA, a concentração dos iniciadores, a temperatura de hibridização e o número de ciclos de desnaturação, hibridização e extensão. Para tanto, extraiu-se o RNA total por meio da reação com fenol-clorofórmio e isotiocianato de guanidina de amostras de testículos de ratos Wistar alimentados com uma ração contendo zinco. Em seguida, gerou-se o cDNA por transcrição reversa. Utilizando-se iniciadores específicos, amplificaram-se o gene de interesse (isoforma testicular da enzima conversora de angiotensina e o gene controle Gliceraldeído-3-Fosfato-Desidrogenase. As amostras foram então aplicadas em gel de agarose e submetidas à eletroforese, coradas em brometo de etídio e visualizadas sob luz ultravioleta. RESULTADOS: Demonstrou-se que a melhor condição reacional para a reação em cadeia pela polimerase da isoforma testicular da enzima conversora de angiotensina e do Gliceraldeído-3-Fosfato-Desidrogenase foi: (1 concentração inicial de cDNA de 2µg, (2 concentração de iniciadores de 200nM, (3 temperatura de hibridização entre 57,5ºC e 60,1ºC e (4 33 ciclos. CONCLUSÃO: Com essa otimização pôde-se minimizar as interferências sobre a técnica, contribuindo-se para a obtenção de dados comparativos a respeito da expressão gênica da enzima conversora de angiotensina testicular.OBJETIVE: The aim of the present work was to optimize the reaction conditions capable of generating variability and introducing systematic errors in the chain reaction of the polymerase used to analyze the gene expression for the testicular isoform of the angiotensin-converting enzyme. METHODS:The cDNA concentration

GATA transcription factors in testicular adrenal rest tumours

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Manon Engels

2017-11-01

Full Text Available Testicular adrenal rest tumours (TARTs are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16, Leydig cell tumours (LCTs; n = 7, adrenal (foetal (n = 6 + adult (n = 10 and testis (foetal (n = 13 + adult (n = 8. We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively, while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes. Incubation of adrenocortical cells (H295RA with ACTH, however, did not induce GATA expression in vitro. Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation.

Polymorphisms in RAI and in genes of nucleotide and base excision repair are not associated with risk of testicular cancer.

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Laska, Magdalena J; Nexø, Bjørn A; Vistisen, Kirsten; Poulsen, Henrik Enghusen; Loft, Steffen; Vogel, Ulla

2005-07-28

Testicular cancer has been suggested to be primed in utero and there is familiar occurrence, particularly brothers and sons of men with testicular cancer have increased risk. Although no specific causative genotoxic agents have been identified, variations in DNA repair capacity could be associated with the risk of testicular cancer. A case-control study of 184 testicular cancer cases and 194 population-based controls living in the Copenhagen Greater Area in Denmark was performed. We found that neither polymorphisms in several DNA repair genes nor alleles of several polymorphisms in the chromosomal of region 19q13.2-3, encompassing the genes ASE, ERCC1, RAI and XPD, were associated with risk of testicular cancer in Danish patients. This is in contrast to other cancers, where we reported strong associations between polymorphisms in ERCC1, ASE and RAI and occurrence of basal cell carcinoma, breast cancer and lung. To our knowledge this is the first study of DNA repair gene polymorphisms and risk of testicular cancer.

[Expression of receptors of estrogens and androgens in the testicular appendices].

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Paredes Esteban, R M; Luque Barona, R J; Velasco Sánchez, B; Rodríguez Vargas, J; Lorite, A; García Ruiz, M

2008-07-01

The appendices or hidátides of the testicle are structures that are considered an embryonic rest. In testicular hidátide estrogen receivers have been demonstrated but in the epididimys the results vary. Has been theorized that the elevation of the estrogen levels in the puberty can produce an inflammation and torsion of hidátide, nevertheless, in the epididimys in which the estrogen expression is not clear (and also they are twisted) the theory is put in doubt. This controversy takes us to the accomplishment of this work. A prospective study is made in 20 testicular appendices, of which 7 from the epididimys are extirpated of patients to whom an escrotal exploration is made in the development of surgery of processes of the inguino-escrotal channel (hidroceles, hernias). Optical microscopy and inmunohistoquímical study are analyzed by means of using prediluted monoclonales antibodies, for receivers of estrogens, androgens and proliferative index. The results were proceed and analyzed by means of SPSS statistical program. All hidátides, testicular and from the epididimarys expressed receivers for estrogens without significant difference among them, not existing differences as far as the location of receiving sayings within the three compartments of hidátide. The number of estrogen receivers was in relation to the age of the patient. Only hidátides from the epididimys fundamentally expressed receivers of located androgens and at level of ductus. We have not found significant relation between the proliferative index and the expression of estrogen receivers. The proliferative index was more elevated at level of ductus. 1) As much the testicular appendices as those from the epididimays expressed receivers of estrogens at level of the three compartments. It makes think about a same embryonic origin, although only the epididimal ones expressed androgen receivers. 2) the observation of estrogen receivers in both types of hidátides, as well as the relation of the

Expression of Selected Markers in Immunohistochemical Diagnosis of Canine and Human Testicular Tumours

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Ciaputa Rafał

2015-04-01

Full Text Available Immunohistochemical profiles of the most common canine testicular tumours, including the Leydig cell tumours, seminomas, and Sertoli cell tumours were analysed, and the results were compared with those obtained in the corresponding types of human testicular neoplasms. The expressions of vimentin, von Willebrand factor (FVIII, chromogranin A, synaptophysin, and MCM3 were quantified. In the case of Sertoli cell tumours, only canine ones were analysed, since this type of tumour is very rarely diagnosed in men. The expression of the analysed proteins in the testicular tumours was similar. The von Willebrand factor exhibited the strongest expression in Leydig cell tumours in dogs and men, while vimentin was expressed more strongly in dogs (96.7% had an intensity at +++ than in men (62.5% had +++ in the Leydigioma. The immunoexpression of MCM3 in seminomas was high in both men and dogs – 90% +++ and 100% +++ respectively. The lack of chromogranin A and synaptophysin was observed in almost 100% of seminomas in men and dogs. This differed from the results obtained for Leydigioma, where chromogranin A was expressed in 70% of dogs at +++ and in 100% of men at ++++. The results may indicate that the antibodies were selected correctly. Their analysis and interpretation provides valuable information concerning the nature of the studied tumours.

Choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and MEK expression in mice.

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Zhang, Jianhai; Zhang, Yufang; Liang, Chen; Wang, Nasui; Zheng, Heping; Wang, Jundong

2016-11-01

Fluoride is known to cause male reproductive toxicity, and the elucidation of its underlying mechanisms is an ongoing research focus in reproductive toxicology and epidemiology. Choline, an essential nutrient, has been extensively studied for its benefits in nervous system yet was rarely discussed for its prospective effect in male reproductive system. This study aims to explore the potential protective role of choline against NaF-induced male reproductive toxicity via MAPK pathway. The male mice were administrated by 150mg/L NaF in drinking water, 5.75g/kg choline in diet, and their combination respectively from maternal gestation to postnatal 15weeks. The results showed that fluoride exposure reduced body weight growth, lowered sperm count and survival percentages, altered testicular histology, down-regulated the mRNA expressions of NGF, Ras, Raf, and MEK genes in testes, as well as significantly decreased the expressions of both NGF and phosphor-MEK proteins in testes. Examination of data from choline-treated mice revealed that choline supplementation ameliorated these fluoride-induced changes. Taken together, our findings suggest that choline supplementation alleviates fluoride-induced testicular toxicity by restoring the NGF and phosphor-MEK expression. The suitable dosage and supplementation periods of choline await further exploration. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of testicular angiotensin-converting enzyme in adult spontaneously hypertensive rats.

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Genka Krasteva

2009-05-01

Full Text Available Recent studies demonstrated that one isoform of angiotensin-converting enzyme named testicular or germinal (tACE is localized in postmeiotic male germ cells and is essential for fertilizing ability of spermatozoa. Hypertension in spontaneously hypertensive rats (SHR is androgen-dependent and reduction in male gametes is reported in this experimental conditions. Expression of tACE was not studied under conditions of spontaneous hypertension. The aim of this work is to characterize immuno-expression of tACE in the testis of adult (16-week-old SHR rats in relation to the changes in blood pressure and serum testosterone level. In 82% of adult SHR, the immuno-expression of tACE followed the normal stage-specific pattern. Destructive testicular changes, germ cells depletion have been observed in 18% of 16-week-old SHR and stronger expression of tACE in stages 8-11 compared to controls was detected. As a result stage specificity in SHR was not as evident as in control. No reaction was found in germ cell depleted tubules in which elongated spermatids were absent. Degenerating germ cells exhibited strong immunostaining comparable to that in residual bodies. The blood pressure was significantly higher in SHR and testosterone levels were more than twice but non-significantly elevated. There was no clear correlation between testicular structural changes, blood pressure level values or serum testosterone levels. Expression of tACE in postmeiotic germ cells, specifically altered by SHR, suggested possible involvement of components of renin-angiotensin system in the process of spermiogenesis. Loss of enzyme expression we found in germ cell depleted tubules in SHR is due to absence of corresponding stages of spermatid differentiation. Therefore, tACE can be used as a marker for germ cell depletion due to hypertension and other pathological conditions.

Anti-MIC2 as a tool in examination of testicular biopsies

DEFF Research Database (Denmark)

Visfeldt, J; Cortes, D; Thorup, J M

1999-01-01

MIC2 is a pseudoautosomal gene localized on X and Y chromosomes. The MIC2 gene product is a glycoprotein expressed on the cell membranes of a number of somatic cells, including Sertoli cells of the testis, but not on the cell membranes of germ cells. In cases of cryptorchidism, a testicular biopsy...... testes which had been cultured in vitro for 7, 14 or 21 days. In all cases the immunohistochemical method with DAKO antibody to the MIC2 gene product was helpful for identification of Sertoli cells and germ cells, and we therefore recommend the use of anti-MIC2 in all testicular biopsies where...

Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

Science.gov (United States)

Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

2014-08-01

The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A cDNA microarray, UniShrimpChip, for identification of genes relevant to testicular development in the black tiger shrimp (Penaeus monodon

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Klinbunga Sirawut

2011-04-01

Full Text Available Abstract Background Poor reproductive maturation in captive male broodstock of the black tiger shrimp (Penaeus monodon is one of the serious problems to the farming industries. Without genome sequence, EST libraries of P. monodon were previously constructed to identify transcripts with important biological functions. In this study, a new version of cDNA microarray, UniShrimpChip, was constructed from the Peneaus monodon EST libraries of 12 tissues, containing 5,568 non-redundant cDNA clones from 10,536 unique cDNA in the P. monodon EST database. UniShrimpChip was used to study testicular development by comparing gene expression levels of wild brooders from the West and East coasts of Thailand and domesticated brooders with different ages (10-, 14-, 18-month-old. Results The overall gene expression patterns from the microarray experiments revealed distinct transcriptomic patterns between the wild and domesticated groups. Moreover, differentially expressed genes from the microarray comparisons were identified, and the expression patterns of eight selected transcripts were subsequently confirmed by reverse-transcriptase quantitative PCR (RT-qPCR. Among these, expression levels of six subunits (CSN2, 4, 5, 6, 7a, and 8 of the COP9 signalosome (CSN gene family in wild and different ages of domesticated brooders were examined by RT-qPCR. Among the six subunits, CSN5 and CSN6 were most highly expressed in wild brooders and least expressed in the 18-month-old domesticated group; therefore, their full-length cDNA sequences were characterized. Conclusions This study is the first report to employ cDNA microarray to study testicular development in the black tiger shrimp. We show that there are obvious differences between the wild and domesticated shrimp at the transcriptomic level. Furthermore, our study is the first to investigate the feasibility that the CSN gene family might have involved in reproduction and development of this economically important

The effect of endocrine disruptors on reproductive parameters and expression of selected testicular genes in male mice in vivo

Czech Academy of Sciences Publication Activity Database

Pěknicová, Jana; Elzeinová, Fatima; Žatecká, Eva; Děd, Lukáš; Dorosh, Andriy

2012-01-01

Roč. 67, Issue Supplement s1 (2012), s. 20 ISSN 1046-7408. [13th International Symposium for Immunology of reproduction "From the roots to the tops of Reproductive Immunology". 22.06.2012-24.06.2012, Varna] R&D Projects: GA ČR(CZ) GA523/09/1793; GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : endocrine disruptors * testicular gene * reproductive parameters * reproduction Subject RIV: DN - Health Impact of the Environment Quality

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

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Jiang, Xin; Bai, Yang; Zhang, Zhiguo [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Xin, Ying, E-mail: xiny@jlu.edu.cn [KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States); Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021 (China); Cai, Lu, E-mail: l0cai001@louisville.edu [The First Hospital of Jilin University, Changchun 130021 (China); KCHRI at the Department of Pediatrics, The University of Louisville, Louisville 40202 (United States)

2014-09-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function

International Nuclear Information System (INIS)

Jiang, Xin; Bai, Yang; Zhang, Zhiguo; Xin, Ying; Cai, Lu

2014-01-01

Diabetes-induced testicular apoptosis is predominantly due to increased oxidative stress. The nuclear factor-erythroid 2-related factor 2 (Nrf2), as a master transcription factor in controlling anti-oxidative systems, is able to be induced by sulforaphane (SFN). To examine whether SFN prevents testicular apoptosis, type 1 diabetic mouse model was induced with multiple low-dose streptozotocin. Diabetic and age-matched control mice were treated with and without SFN at 0.5 mg/kg daily in five days of each week for 3 months and then kept until 6 months. Diabetes significantly increased testicular apoptosis that was associated with endoplasmic reticulum stress and mitochondrial cell death pathways, shown by the increased expression of C/EBP homologous protein (CHOP), cleaved caspase-12, Bax to Bcl2 expression ratio, and cleaved caspase-3. Diabetes also significantly increased testicular oxidative damage, inflammation and fibrosis, and decreased germ cell proliferation. All these diabetic effects were significantly prevented by SFN treatment for the first 3 months, and the protective effect could be sustained at 3 months after SFN treatment. SFN was able to up-regulate Nrf2 expression and function. The latter was reflected by the increased phosphorylation of Nrf2 at Ser40 and expression of Nrf2 downstream antioxidants at mRNA and protein levels. These results suggest that type 1 diabetes significantly induced testicular apoptosis and damage along with increasing oxidative stress and cell death and suppressing Nrf2 expression and function. SFN is able to prevent testicular oxidative damage and apoptosis in type 1 diabetes mice, which may be associated with the preservation of testicular Nrf2 expression and function under diabetic condition. - Highlights: • Sulforaphane (SFN) could attenuate diabetes-induced germ cell apoptosis. • SFN could preserve germ cell proliferation under diabetic conditions. • SFN testicular protection was sustained until 3 months after

Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

Science.gov (United States)

Puar, Troy; Engels, Manon; van Herwaarden, Antonius E; Sweep, Fred C G J; Hulsbergen-van de Kaa, Christina; Kamphuis-van Ulzen, Karin; Chortis, Vasileios; Arlt, Wiebke; Stikkelbroeck, Nike; Claahsen-van der Grinten, Hedi L; Hermus, Ad R M M

2017-02-01

Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 × 105 (CYP11B1), 1.8 × 102 (CYP11B2), and 6.3 × 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 × 101 (LHCGR) and 9.3 × 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia. Copyright © 2017 by the Endocrine Society

N-cadherin Expression in Testicular Germ Cell and Gonadal Stromal Tumors

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Daniel J. Heidenberg, Joel H. Barton, Denise Young, Michael Grinkemeyer, Isabell A. Sesterhenn

2012-01-01

Full Text Available Neural-cadherin is a member of the cadherin gene family encoding the N-cadherin protein that mediates cell adhesion. N-cadherin is a marker of Sertoli cells and is also expressed in germ cells of varying stages of maturation. The purpose of this study was to determine the presence and distribution of this protein by immunohistochemistry in 105 germ cell tumors of both single and mixed histological types and 12 gonadal stromal tumors. Twenty-four germ cell tumors consisted of one cell type and the remaining were mixed. Of the 23 seminomas in either pure or mixed tumors, 74% were positive. Two spermatocytic seminomas were positive. Of the 83 cases with yolk sac tumor, 99% were positive for N-cadherin. The teratomas were positive in 73% in neuroectodermal and / or glandular components. In contrast, 87% of embryonal carcinomas did not express N-cadherin. Only 17% of the syncytiotrophoblastic cells were positive for N-cadherin. In conclusion, N-cadherin expression is very helpful in the identification of yolk sac tumors. In addition to glypican-3 and Sal-like protein 4, N-cadherin can be beneficial for the diagnosis and classification of this subtype of testicular germ cell tumor. Nine of the 12 gonadal stromal tumors were positive to a variable extent.

Endogenous biotin expression in renal and testicular tumours and literature review.

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Fahmy, Nader; Woo, Mark; Alameldin, Mona; Lee, Joe King; MacDonald, Kyle; Goneau, Lee W; Cadieux, Peter; Burton, Jeremy; Pautler, Stephen

2014-07-01

The aim of this study was to examine endogenous biotin levels in tumour specimens collected from patients with renal and testicular tumours and compare them to the surrounding non-neoplastic surgical margin. Frozen samples were obtained from the Ontario Tumour Bank. Renal and testicular tumour tissue were included in this study. Normal tissue from the negative surgical margins of each tumour served as a control. Biotin detection in tissue specimens was determined using immunohistochemistry (IHC). Specimens collected from 56 patients (36 men and 20 women) were included in this study. Histopathology of the 52 renal tumours included 31 (60%) conventional type RCC, 5 (10%) chromophobe RCC, 5 (10%) papillary RCC, 1 (2%) oncocytoma and 10 (19%) upper tract urothelial carcinoma (UC). The 4 testicular tumours included 1 seminomatous (25%) germ cell tumour and 3 (75%) non seminomatous germ cell tumours. No biotin signal was perceived in all tested tumour samples. Endogenous biotin expression was detected in the matching non-neoplastic surgical margin of tested renal tissues. This lack of staining may prove to be a valuable tool in future studies.

Effect of an Organic Trace Mineral Premix on the Semen Quality, Testicular Morphology and Gene Expression Related to Testosterone Synthesis of Male Broiler Breeders

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T Shan

Full Text Available ABSTRACT In order to investigate the effect of organic trace minerals premix (OTM on the reproductive performance of breeder roosters, a total of 240 San Huang roosters (23 weeks of age were randomly divided into two treatments with six replicates of 20 roosters each. The first group (n = 120 was fed a basal diet containing an inorganic trace minerals premix (ITM and the other group (n = 120 was fed the basal diet in which ITM was replaced by OTM. The experiment period was 22 weeks. Semen from one randomly-selected rooster per replicate was collected two weeks after the beginning of the experiment and other 10 times every two weeks. Another rooster per replicate was randomly selected at 30, 35, and 45 weeks of age, and sacrificed. Results showed that OTM did not affect relative organ weights. There was a significant increase in semen parameters in OTM group (p<0.05, such as semen volume, semen density, and semen motility from 31 to 35 weeks. OTM-fed roosters presented higher serum testosterone levels at 45 weeks of age, as well as higher testicular mRNA expression of the genes 3-beta dehydrogenase 2 (HSD3B2 and cytochrome P450 17A1 (CYP17A1 in the OTM-fed group at 45 weeks of age compared with those fed ITM (p<0.05. Considering the results of the present study, it was concluded that feeding organic instead of inorganic trace minerals to male broilers breeders improves semen quality, which may be attributed to their better testicular development and higher expression of enzymes related to testosterone synthesis.

Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring

International Nuclear Information System (INIS)

Hsu, P.-C.; Pan, M.-H.; Li, L.-A.; Chen, C.-J.; Tsai, S.-S.; Guo, Y.L.

2007-01-01

Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB, 2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways in male offspring are relatively unknown. The purpose was to determine whether epididymal sperm function and expression of apoptosis-related genes were induced or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring were killed and the epididymal sperm counts, motility, velocity, reactive oxygen species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular histopathology, apoptosis-related gene expression and caspase activation were assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of 1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132-exposed offspring produced significantly higher levels of ROS than the controls; ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132 group, p53 was significantly induced and caspase-3 was inhibited. In the high-dose group, activation of caspase-3 and -9 was significantly increased, while the expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene expression and caspase activation data may provide insight into the mechanisms by which exposure to low-dose or high-dose PCB 132 affects reproduction in male offspring in rats. Because the doses of PCB 132 administered to the dams were approximately 625-fold in low-dose group and 6250-fold higher in high-dose group than the concentration in human tissue levels, the concentrations are not biologically or environmentally relevant. Further studies using environmentally relevant doses are needed for hazard identification

Testicular cancer from diagnosis to epigenetic factors

Science.gov (United States)

Boccellino, Mariarosaria; Vanacore, Daniela; Zappavigna, Silvia; Cavaliere, Carla; Rossetti, Sabrina; D’Aniello, Carmine; Chieffi, Paolo; Amler, Evzen; Buonerba, Carlo; Di Lorenzo, Giuseppe; Di Franco, Rossella; Izzo, Alessandro; Piscitelli, Raffaele; Iovane, Gelsomina; Muto, Paolo; Botti, Gerardo; Perdonà, Sisto; Caraglia, Michele; Facchini, Gaetano

2017-01-01

Testicular cancer (TC) is one of the most common neoplasms that occurs in male and includes germ cell tumors (GCT), sex cord-gonadal stromal tumors and secondary testicular tumors. Diagnosis of TC involves the evaluation of serum tumor markers alpha-fetoprotein, human chorionic gonadotropin and lactate dehydrogenase, but clinically several types of immunohistochemical markers are more useful and more sensitive in GCT, but not in teratoma. These new biomarkers are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related cells but not in normal adult germ cells and they include PLAP, OCT3/4 (POU5F1), NANOG, SOX2, REX1, AP-2γ (TFAP2C) and LIN28. Gene expression in GCT is regulated, at least in part, by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation. There are different epigenetic modifications in TG-subtypes that reflect the normal developmental switch in primordial germ cells from an under- to normally methylated genome. The main purpose of this review is to illustrate the findings of recent investigations in the classification of male genital organs, the discoveries in the use of prognostic and diagnostic markers and the epigenetic aberrations mainly affecting the patterns of DNA methylation/histone modifications of genes (especially tumor suppressors) and microRNAs (miRNAs). PMID:29262668

The Effect of Propiconazole and Protective Effects of Selenium Gene Expression Profile of Caspase 9 in the Testicular Tissue of Male Sprague Dawley (SD Rats

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S Rashidi pouya

2016-08-01

Full Text Available Background & aim: Conazoles including imidazoles or triazoles are anti- fungal agents widely used to prevent fungal growth and their infections. Propiconazole placed in this group is a systemic fungicide used widely for detoxification of cereal seeds especially rice in Iran and other countries. This fungicide were designed to inhibit a specific cytochrome P450, CYP51 (lanosterol-14-α- demethylase, a critical step in the biosynthesis of ergosterol, a steroid required for the formation of the fungal cell wall. In the present experimental study, the effect of propiconazole on Caspase 9 gene expression profile as an initiator of apoptotic process and protective effect of selenium were investigated. Methods: Forty SD rats were divided into 10 groups of 4,  including : control , sham1 (solvent of propiconazole, distilled water, sham 2 (solvent of selenium, normal saline and 1 group received 0.5 mg/kg selenium ,3 groups received propiconazole in doses of 10,50,75  mg/kg and 3 groups received propiconazole in doses of 10,50,75 mg/kg propiconazole with 0.5 mg/kg of selenium. Injections were intrapritoneal for two weeks in alternate days. Then, using RT-PCR and Total Lab program gene expression of caspase-9 testicular of all groups were studied. Data were analyzed using descriptive statistics. Results:  A significant increase of caspase 9 expression were observed among all experimental groups compared to control and sham groups. These findings indicated that 0.5 mg/kg selenium is not a suitable dose to create protection in this experimental study.  Conclusion: The significant increase in Caspase 9 gene expression profile observed in all experimental groups as compared to control suggests activation of apoptosis and inefficacy of selenium to protect the testis against induced damages.

Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

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M. V. Nemtsova

2015-03-01

Full Text Available Testicular tumors are the most common form of solid cancer in young men. According to the 2004 WHO classification, testicular germ cell tumors (TGCT may present with different histological types. Embryonic cells of varying grade may be a source of TGCT and the occurrence of this type of tumors is directly related to the formation of a pool of male sex cells and gametogenesis. The paper gives information on mo- lecular stages for the process of formation of male sex cells in health, as well as ways of their impairments leading to TGCT. An investigation of the profiles of gene expression and the spectrum of molecular damages revealed genes responsible for a predisposition to the sporadic and hereditary forms of TGCT. The paper presents the current molecular genetic and clinicomorphological characteristics of TGCT. 

Sulforaphane Prevents Angiotensin II-Induced Testicular Cell Death via Activation of NRF2

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Yonggang Wang

2017-01-01

Full Text Available Although angiotensin II (Ang II was reported to facilitate sperm motility and intratesticular sperm transport, recent findings shed light on the efficacy of Ang II in stimulating inflammatory events in testicular peritubular cells, effect of which may play a role in male infertility. It is still unknown whether Ang II can induce testicular apoptotic cell death, which may be a more direct action of Ang II in male infertility. Therefore, the present study aims to determine whether Ang II can induce testicular apoptotic cell death and whether this action can be prevented by sulforaphane (SFN via activating nuclear factor (erythroid-derived 2-like 2 (NRF2, the governor of antioxidant-redox signalling. Eight-week-old male C57BL/6J wild type (WT and Nrf2 gene knockout mice were treated with Ang II, in the presence or absence of SFN. In WT mice, SFN activated testicular NRF2 expression and function, along with a marked attenuation in Ang II-induced testicular oxidative stress, inflammation, endoplasmic reticulum stress, and apoptotic cell death. Deletion of the Nrf2 gene led to a complete abolishment of these efficacies of SFN. The present study indicated that Ang II may result in testicular apoptotic cell death, which can be prevented by SFN via the activation of NRF2.

Effects of electromagnetic radiation on morphology and TGF-β3 expression in mouse testicular tissue.

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Luo, Yaning; Wang, Xiaowu; Chen, Yongbin; Xu, Shenglong; Ding, Guirong; Shi, Changhong

2013-08-09

Exposure to electromagnetic pulses in certain doses may lead to increase in the permeability of the blood testes barrier (BTB) in mice, which in turn affects spermatogenesis, penetration and spermiation. TGF-β3 is a key molecule involved in BTB permeability via regulation of tight junction proteins, and it participates in regulating spermatogenesis, synthesis of steroids and production of the extracellular matrix in testicular tissue. Therefore, it is hypothesized that TGF-β3 plays important roles in electromagnetic pulse (EMP)-induced changes in BTB permeability. In the present study, we carried out whole-body irradiation on mice using EMP of different intensities. No obvious pathological changes or significant increase in apoptosis was detected in testicular tissues after exposure to 100 and 200 pulses of intensity 200kV/m; however, with 400 pulses we observed the degeneration and shrinkage of testicular tissues along with a significant increase in apoptotic rate. Moreover, in the 100- and 200-EMP groups, a non-significant increase in TGF-β3 mRNA and protein expression was observed, whereas in the 400-EMP group a significant increase was observed (P<0.05). These results indicate that increase in the apoptotic rate of testicular tissues and increase in TGF-β3 expression may be one of the mechanisms for EMP-induced increase in BTB permeability in mice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Intersex related gene expression profiles in clams Scrobicularia plana: Molecular markers and environmental application

International Nuclear Information System (INIS)

Ciocan, Corina M.; Cubero-Leon, Elena; Langston, William J.; Pope, Nick; Cornelius, Keith; Hill, E.M.; Alvarez-Munoz, Diana; Indiveri, Paolo; Lerebours, Adelaide; Minier, Christophe; Rotchell, Jeanette M.

2015-01-01

Highlights: • Expression of intersex-related genes was analysed in clam gonads sampled from the Channel. • Genes were differentially expressed at sites with varying levels of intersex and contaminants. • Correlations between gene expressions, key contaminants and sampling sites were identified. • No single gene expression studied correlated with intersex incidence. - Abstract: Intersex, the appearance of female characteristics in male gonads, has been identified in several aquatic species. It is a widespread phenomenon in populations of the bivalve, Scrobicularia plana, from the southwest coast of the U.K. Genes previously identified as differentially expressed (ferritin, testicular haploid expressed gene, THEG, proliferating cell nuclear antigen, PCNA; receptor activated protein kinase C, RACK; cytochrome B, CYB; and cytochrome c oxidase 1, COX1) in intersex clams relative to normal male clams, were selected for characterisation and an environmental survey of the Channel region. Transcripts were significantly differentially expressed at sites with varying intersex incidence and contaminant burdens. Significant correlations between specific gene expressions, key contaminants and sampling locations have been identified, though no single gene was associated with intersex incidence. The results highlight the difficulty in understanding the intersex phenomenon in molluscs where there is still a lack of knowledge on the control of normal reproduction

Variation in bleomycin hydrolase gene is associated with reduced survival after chemotherapy for testicular germ cell cancer

NARCIS (Netherlands)

de Haas, Esther C.; Zwart, Nynke; Meijer, Coby; Nuver, Janine; Boezen, H. Marike; Suurmeijer, Albert J. H.; Hoekstra, Harald J.; van der Steege, Gerrit; Sleijfer, Dirk Th.; Gietema, Jourik A.

2008-01-01

Purpose Response to chemotherapy may be determined by gene polymorphisms involved in metabolism of cytotoxic drugs. A plausible candidate is the gene for bleomycin hydrolase (BLMH), an enzyme that inactivates bleomycin, an essential component of chemotherapy regimens for disseminated testicular

Effects of maternal acrolein exposure during pregnancy on testicular testosterone production in fetal rats.

Science.gov (United States)

Yang, Yuzhuo; Zhang, Zhe; Zhang, Hongliang; Hong, Kai; Tang, Wenhao; Zhao, Lianming; Lin, Haocheng; Liu, Defeng; Mao, Jiaming; Wu, Han; Jiang, Hui

2017-07-01

Acrolein has been reported to have diverse toxic effects on various organs, including the reproductive system. However, little is known regarding the effects of maternal acrolein exposure on testicular steroidogenesis in male offspring. The present study investigated the effects of acrolein on fetal testosterone production and associated genes. Pregnant Sprague‑Dawley rats were intraperitoneally injected with vehicle (normal saline) or 1, 2 or 5 mg/kg acrolein from gestational day (GD) 14‑20, and fetal testes were examined on GD 21. Fetal body and testicular weights were markedly reduced in pups following exposure to high doses of acrolein (5 mg/kg) in late pregnancy. Notably, in utero exposure of 5 mg/kg acrolein significantly decreased the testicular testosterone level and downregulated the expression levels of steroidogenic acute regulatory protein (StAR) and 3β‑hydroxysteroid dehydrogenase (3β‑HSD), whereas the levels of other steroidogenic enzymes, including scavenger receptor class B, cholesterol side‑chain cleavage enzyme and steroid 17 alpha‑hydroxylase/17,20 lyase, were unaffected. Furthermore, the 3β‑HSD immunoreactive area in the interstitial region of the fetal testes was reduced at a 5 mg/kg dose, whereas the protein expression levels of 4‑hydroxynonenalwere dose‑dependently increased following maternal exposure to acrolein. mRNA expression levels of insulin‑like factor 3, a critical gene involved in testicular descent, were unaltered following maternal acrolein exposure. Taken together, the results of the present study suggested that maternal exposure to high doses of acrolein inhibited fetal testosterone synthesis, and abnormal expression of StAR and 3β‑HSD may be associated with impairment of the steroidogenic capacity.

Characterization of the testicular, epididymal and endocrine phenotypes in the Leuven Vdr-deficient mouse model

DEFF Research Database (Denmark)

Blomberg Jensen, Martin; Lieben, Liesbet; Nielsen, John E

2013-01-01

Vitamin D is a key factor for calcium and bone homeostasis, but signalling through the vitamin D receptor (VDR) seems also to be important for testicular function. To test the functional role of vitamin D signalling we examined the male reproductive system of the Leuven Vdr-ablated (Vdr(-/-)) mice......, previously established as a model for hereditary vitamin D-resistant rickets. We investigated reproductive hormones, changes in gene expression and histological phenotype of eleven Vdr(-/-), eight Vdr(+/-) and nine Vdr(+/+) mice. Testicular and epididymal histology were grossly normal in Vdr(-/-) mice...... expressions of ERα and the estrogen-target gene Aqp9 were higher. In conclusion, vitamin D seems dispensable for murine spermatogenesis and sex hormone production, but aberrant estrogen-signalling may elicit some of the VDR-mediated effects on male reproduction....

Critical Function of PRDM2 in the Neoplastic Growth of Testicular Germ Cell Tumors

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Erika Di Zazzo

2016-12-01

Full Text Available Testicular germ cell tumors (TGCTs derive from primordial germ cells. Their maturation is blocked at different stages, reflecting histological tumor subtypes. A common genetic alteration in TGCT is a deletion of the chromosome 1 short arm, where the PRDM2 gene, belonging to the Positive Regulatory domain gene (PRDM family, is located. Expression of PRDM2 gene is shifted in different human tumors, where the expression of the two principal protein forms coded by PRDM2 gene, RIZ1 and RIZ2, is frequently unbalanced. Therefore, PRDM2 is actually considered a candidate tumor suppressor gene in different types of cancer. Although recent studies have demonstrated that PRDM gene family members have a pivotal role during the early stages of testicular development, no information are actually available on the involvement of these genes in TGCTs. In this article we show by qRT-PCR analysis that PRDM2 expression level is modulated by proliferation and differentiation agents such as estradiol, whose exposure during fetal life is probably an important risk factor for TGCTs development in adulthood. Furthermore in normal and cancer germ cell lines, PRDM2 binds estradiol receptor α (ERα and influences proliferation, survival and apoptosis, as previously reported using MCF-7 breast cancer cell line, suggesting a potential tumor-suppressor role in TGCT formation.

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

International Nuclear Information System (INIS)

Schrader, Mark; Burger, Angelika M; Müller, Markus; Krause, Hans; Straub, Bernd; Schostak, Martin; Schulze, Wolfgang; Lauke, Heidrun; Miller, Kurt

2002-01-01

The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT). Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression. These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status

The differentiation status of primary gonadal germ cell tumors correlates inversely with telomerase activity and the expression level of the gene encoding the catalytic subunit of telomerase

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Schulze Wolfgang

2002-11-01

Full Text Available Abstract Background The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT, which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT. Methods Telomerase activity (TA was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients. Results High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome showed no telomerase activity and only minimal hTERT expression. Conclusions These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status.

Testicular microlithiasis and testicular cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Rafaelsen, Søren Rafael; Møller, Henrik

2016-01-01

Purpose To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. Methods A systematic literature search was performed of original articles in English published 1998...... In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune–Albright syndrome, cryptorchidism, infertility and familial disposition of testicular...... cancer. Conclusion Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular...

[Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

Science.gov (United States)

Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

2012-01-01

Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

Anti-MIC2 as a tool in examination of testicular biopsies

DEFF Research Database (Denmark)

Visfeldt, J; Cortes, Dina; Thorup, J M

1999-01-01

MIC2 is a pseudoautosomal gene localized on X and Y chromosomes. The MIC2 gene product is a glycoprotein expressed on the cell membranes of a number of somatic cells, including Sertoli cells of the testis, but not on the cell membranes of germ cells. In cases of cryptorchidism, a testicular biopsy...... transverse section is lower than 1% of the lowest normal age-matched value. Besides Sertoli cells the seminiferous tubules in undescended testes contain only a few germ cells, and it may be difficult to pinpoint the germ cells in small biopsies. Especially in nonpalpable testes their number may be heavily...... reduced. A reliable identification of germ cells may also be difficult in cultures of testicular biopsies from undescended testes. Against this background, we tried the use of an immunohistochemical method with DAKO antibody to the MIC2 gene product (MIC2, 12 E7, code no. M3601) in order to obtain...

Ghrelin and NUCB2/Nesfatin-1 expression in unilateral testicular torsion-induced rats with and without N-acetylcysteine.

Science.gov (United States)

Sarac, M; Bakal, U; Tartar, T; Kuloglu, T; Yardim, M; Artas, G; Aydin, S; Kazez, A

2017-08-15

Testicular torsion (TT) is a common urological problem in the field of pediatric surgery. The degree and duration of torsion determines the degree of testicular damage; however, its effects on the expression of octanoylated ghrelin and nucleobindin 2 (NUCB2) /nesfatin-1 synthetized from testicular tissue remain unclear. We explored the effects of experimentally induced unilateral TT on serum and contralateral testicular tissue ghrelin and NUCB2/nesfatin-1 levels, and determined whether N-acetyl cysteine (NAS) treatment had any effects on their expression. A total of 42 Wistar Albino strain rats were divided into 7 groups: Group (G) I control, GII sham, GIII 12-hour torsion, GIV 12-hour torsion + detorsion + 100 mg/kg NAS, GV 24-hour torsion, GVI 24-hour torsion + detorsion + 100 mg/kg NAS, and GVII 100 mg/kg NAS. Octanoylated ghrelin and NUCB2/nesfatin-1 concentrations were evaluated in serum using the ELISA method and in testicular tissue with immunohistochemical methods. Immunoreactivity of octanoylated ghrelin significantly increased in GI compared to GIII, GV, and GVI (p<0.05). NUCB2/nesfatin-1 immunoreactivity increased in GV and GVIII relative to GI (p<0.05). In the 12-hour torsion group, a significant decrease in octanoylated ghrelin levels with NAS treatment was observed; however, in the 24-hour torsion group, a significant decrease was not observed. In the 12-hour torsion + NAS treatment group, a significant change was not observed in NUCB2/nesfatin-1 expression. Following 24-hour torsion, an increase in NUCB2/nesfatin-1 levels was observed, and NAS treatment did not reverse this increase. It was determined that increases in the expression of octanoylated ghrelin and NUCB2/nesfatin-1, the latter of which was a result of TT, reflect damage in this tissue. Importantly, NAS treatment could prevent this damage. Thus, there may be a clinical application for the combined use of NAS and octanoylated ghrelin in preventing TT-related infertility.

Uropathogenic E. coli induce different immune response in testicular and peritoneal macrophages: implications for testicular immune privilege.

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Sudhanshu Bhushan

Full Text Available Infertility affects one in seven couples and ascending bacterial infections of the male genitourinary tract by Escherichia coli are an important cause of male factor infertility. Thus understanding mechanisms by which immunocompetent cells such as testicular macrophages (TM respond to infection and how bacterial pathogens manipulate defense pathways is of importance. Whole genome expression profiling of TM and peritoneal macrophages (PM infected with uropathogenic E. coli (UPEC revealed major differences in regulated genes. However, a multitude of genes implicated in calcium signaling pathways was a common feature which indicated a role of calcium-dependent nuclear factor of activated T cells (NFAT signaling. UPEC-dependent NFAT activation was confirmed in both cultured TM and in TM in an in vivo UPEC infectious rat orchitis model. Elevated expression of NFATC2-regulated anti-inflammatory cytokines was found in TM (IL-4, IL-13 and PM (IL-3, IL-4, IL-13. NFATC2 is activated by rapid influx of calcium, an activity delineated to the pore forming toxin alpha-hemolysin by bacterial mutant analysis. Alpha-hemolysin suppressed IL-6 and TNF-α cytokine release from PM and caused differential activation of MAP kinase and AP-1 signaling pathways in TM and PM leading to reciprocal expression of key pro-inflammatory cytokines in PM (IL-1α, IL-1β, IL-6 downregulated and TM (IL-1β, IL-6 upregulated. In addition, unlike PM, LPS-treated TM were refractory to NFκB activation shown by the absence of degradation of IκBα and lack of pro-inflammatory cytokine secretion (IL-6, TNF-α. Taken together, these results suggest a mechanism to the conundrum by which TM initiate immune responses to bacteria, while maintaining testicular immune privilege with its ability to tolerate neo-autoantigens expressed on developing spermatogenic cells.

Protective effects of sea cucumber (Holothuria atra) extract on testicular dysfunction induced by immune suppressant drugs in Wistar rats.

Science.gov (United States)

Saad, D Y; Soliman, M M; Mohamed, A A; Youssef, G B

2018-04-23

The current study was aimed to evaluate the protective effect of Holothurian atra (HA) extract; naturally occurring marine resource, against methotrexate (MTX) induced testicular dysfunction. Mature rats received either MTX (20 mg/kg, intraperitoneally) or saline on the 7th day of experiment al design. Seven days prior and after MTX-injection, rats received HA at dose of 300 mg/kg intragastrically (HA + MTX group; HA group alone). Serum was extracted and testicular tissues were examined for the changes in serum biochemistry (liver & kidney biomarkers, testicular hormones and antioxidants), molecular and histopthological alterations using RT-PCR and immunohistochemistry. MTX-injected rats induced alteration in all testicular parameters. Prior administration of HA ameliorated the MTX-induced oxidative stress. HA administration normalised MTX-induced decrease in serum levels of interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), reproductive hormones (FSH, LH and testosterone) and antioxidants GST, SOD and catalase. MTX-injected rats down-regulated mRNA expression of GST, SOD, steroidogenesis associated genes, IFN-γ, Bcl2 and NFKB. MTX up-regulated BAX expression and caspase 9 immunoreactivity that were ameliorated in HA + MTX group. Collectively, HA ameliorated and restored all altered genes. In conclusion, HA is a promising supplement that is helpful in protection against testicular cytotoxicity and dysfunction induced by methotrexate. © 2018 Blackwell Verlag GmbH.

Testicular Microlithiasis: Is It Associated with Testicular Cancer?

Science.gov (United States)

... Is there a link between testicular microlithiasis and testicular cancer? Answers from Erik P. Castle, M.D. Testicular microlithiasis (tes-TIK-yoo- ... studies show a relationship between testicular microlithiasis and testicular cancer. However, it remains unclear whether having testicular microlithiasis ...

GnRH-agonist implantation of prepubertal male cats affects their reproductive performance and testicular LH receptor and FSH receptor expression.

Science.gov (United States)

Mehl, N S; Khalid, M; Srisuwatanasagul, S; Swangchan-Uthai, T; Sirivaidyapong, S

2016-03-15

This study was conducted to investigate the effect of GnRH-agonist implantation in prepubertal tomcats on sexual behavior, reproductive performance, and expression of testicular LH receptor (LHR) and FSH receptor (FSHR) and also to compare the testicular characteristics, LHR and FSHR expression between prepubertal and adult tomcats. In experiment 1, 3-month-old tomcats (n = 6/group) were either treated with or left without 4.7 mg deslorelin implants. Semen collection and evaluation were performed just before castration at 48 weeks after treatment; removed testes were analyzed for mRNA and protein expression of LHR and FSHR. We were able to collect semen from six non-treated cats, whereas in treated cats, semen was uncollectable. The results revealed that sexual behavior was absent in the implanted cats throughout the study period. Testicular volume was found to decrease from 30 weeks after treatment onward in the implanted cats compared to the controls (P score, seminiferous tubule diameter, and LHR protein expression were found lower in the implanted cats (P reproductive function without any adverse effects for at least 48 weeks in male cats. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular cloning, expression analysis and transcript localization of testicular orphan nuclear receptor 2 in the male catfish, Clarias batrachus.

Science.gov (United States)

Murugananthkumar, R; Akhila, M V; Rajakumar, A; Mamta, S K; Sudhakumari, C C; Senthilkumaran, B

2016-12-01

Testicular receptor 2 (TR2; also known as Nr2c1) is one of the first orphan nuclear receptors identified and known to regulate various physiological process with or without any ligand. In this study, we report the cloning of full length nr2c1 and its expression analysis during gonadal development, seasonal testicular cycle and after human chorionic gonadotropin (hCG) induction. In addition, in situ hybridization (ISH) was performed to localize nr2c1 transcripts in adult testis and whole catfish (1day post hatch). Tissue distribution and gonadal ontogeny studies revealed high expression of nr2c1 in developing and adult testis. Early embryonic stage-wise expression of nr2c1 seems to emphasize its importance in cellular differentiation and development. Substantial expression of nr2c1 during pre-spawning phase and localization of nr2c1 transcripts in sperm/spermatids were observed. Significant upregulation after hCG induction indicate that nr2c1 is under the regulation of gonadotropins. Whole mount ISH analysis displayed nr2c1 expression in notochord indicating its role in normal vertebrate development. Taken together, our findings suggest that nr2c1 may have a plausible role in the testicular and embryonic development of catfish. Copyright © 2015. Published by Elsevier Inc.

Copy number variations of E2F1: a new genetic risk factor for testicular cancer.

Science.gov (United States)

Rocca, Maria Santa; Di Nisio, Andrea; Marchiori, Arianna; Ghezzi, Marco; Opocher, Giuseppe; Foresta, Carlo; Ferlin, Alberto

2017-03-01

Testicular germ cell tumor (TGCT) is one of the most heritable forms of cancer. In last years, many evidence suggested that constitutional genetic factors, mainly single nucleotide polymorphisms, can increase its risk. However, the possible contribution of copy number variations (CNVs) in TGCT susceptibility has not been substantially addressed. Indeed, an increasing number of studies have focused on the effect of CNVs on gene expression and on the role of these structural genetic variations as risk factors for different forms of cancer. E2F1 is a transcription factor that plays an important role in regulating cell growth, differentiation, apoptosis and response to DNA damage. Therefore, deficiency or overexpression of this protein might significantly influence fundamental biological processes involved in cancer development and progression, including TGCT. We analyzed E2F1 CNVs in 261 cases with TGCT and 165 controls. We found no CNVs in controls, but 17/261 (6.5%) cases showed duplications in E2F1 Blot analysis demonstrated higher E2F1 expression in testicular samples of TGCT cases with three copies of the gene. Furthermore, we observed higher phosphorylation of Akt and mTOR in samples with E2F1 duplication. Interestingly, normal, non-tumoral testicular tissue in patient with E2F1 duplication showed lower expression of E2F1 and lower AKT/mTOR phosphorylation with respect to adjacent tumor tissue. Furthermore, increased expression of E2F1 obtained in vitro in NTERA-2 testicular cell line induced increased AKT/mTOR phosphorylation. This study suggests for the first time an involvement of E2F1 CNVs in TGCT susceptibility and supports previous preliminary data on the importance of AKT/mTOR signaling pathway in this cancer. © 2017 Society for Endocrinology.

Unilateral testicular tumour associated to congenital adrenal hyperplasia: Failure of specific tumoral molecular markers to discriminate between adrenal rest and leydigioma.

Science.gov (United States)

Fenichel, P; Bstandig, B; Roger, C; Chevallier, D; Michels, J-F; Sadoul, J-L; Hieronimus, S; Brucker-Davis, F

2008-11-01

Testicular adrenal rest tumours are frequently associated with congenital adrenal hyperplasia (CAH). These ACTH-dependent tumours cannot be easily distinguished histologically from Leydig-cell tumours. We report the case of a 30-year-old man who was explored for infertility, azoospermia and unilateral testicular tumour. High levels of 17-OH progesterone and ACTH, low cortisol and undetectable gonadotropins levels, associated to bilateral adrenal hyperplasia, led to the diagnosis of CAH by 21-OH deficiency with a composite heterozygoty. The testicular tumour was first considered as adrenal rest. However, histological analysis of this unilateral painful tumour showed a steroid-hormone-secreting cell proliferation with atypical and frequent mitosis. To discriminate between a benign adrenal rest tumour and a possible malignant leydigioma, tumoral expression of specific gene products was analyzed by RT-PCR. No 11-beta-hydroxylase nor ACTH receptor mRNAs could be found in the tumour, which did not behave like usual adrenal rest cells. For this unilateral testicular tumour, the lack of adrenal-specific markers associated with a high rate of mitosis and pleiomorphism supported a leydigian origin with malignant potential. However, lack of tumoral LH-R mRNA expression and a tumour-free 3-year follow-up led us to retain the diagnosis of adrenal rest tumour with loss of adrenal gene expression and progressive autonomous behaviour.

Gene expression during ovarian differentiation in parasitic and non-parasitic lampreys: implications for fecundity and life history types.

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Spice, Erin K; Whyard, Steven; Docker, Margaret F

2014-11-01

Lampreys diverged from the jawed vertebrate lineage approximately 500million years ago. Lampreys undergo sex differentiation much later than most other vertebrates, and ovarian differentiation occurs several years before testicular differentiation. The genetic basis of lamprey sex differentiation is of particular interest both because of the phylogenetic importance of lampreys and because of their unusual pattern of sex differentiation. As well, differences between parasitic and non-parasitic lampreys may first become evident at ovarian differentiation. However, nothing is known about the genetic basis of ovarian differentiation in lampreys. This study examined potential differences in gene expression before, during, and after ovarian differentiation in parasitic chestnut lamprey Ichthyomyzon castaneus and non-parasitic northern brook lamprey Ichthyomyzonfossor. Eight target genes (17β-hydroxysteroid dehydrogenase, germ cell-less, estrogen receptor β, insulin-like growth factor 1 receptor, daz-associated protein 1, cytochrome c oxidase subunit III, Wilms' tumour suppressor protein 1, and dehydrocholesterol reductase 7) were examined. Northern brook lamprey displayed higher expression of cytochrome c oxidase subunit III, whereas chestnut lamprey displayed higher expression of insulin-like growth factor 1 receptor; these genes may be involved in apoptosis and oocyte growth, respectively. Presumptive male larvae had higher expression of Wilms' tumour suppressor protein 1, which may be involved in the undifferentiated gonad and/or later testicular development. Differentiated females had higher expression of 17β hydroxysteroid dehydrogenase and daz-associated protein 1, which may be involved in female development. This study is the first to identify genes that may be involved in ovarian differentiation and fecundity in lampreys. Copyright © 2014 Elsevier Inc. All rights reserved.

Testicular descent: INSL3, testosterone, genes and the intrauterine milieu

DEFF Research Database (Denmark)

Bay, Katrine; Main, Katharina M; Toppari, Jorma

2011-01-01

Complete testicular descent is a sign of, and a prerequisite for, normal testicular function in adult life. The process of testis descent is dependent on gubernacular growth and reorganization, which is regulated by the Leydig cell hormones insulin-like peptide 3 (INSL3) and testosterone. Investi...

Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice

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De Gendt Karl

2009-08-01

Full Text Available Abstract Background Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM. Methods This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs on the Sertoli cells (SCARKO, mice with a ubiquitous loss of androgen ARs (ARKO, hypogonadal (hpg mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO and ARKO (hpg.ARKO mice. Results Microscopic TM was seen in 94% of hpg.ARKO mice (n = 16 and the mean number of microliths per testis was 81 +/- 54. Occasional small microliths were seen in 36% (n = 11 of hpg testes (mean 2 +/- 0.5 per testis and 30% (n = 10 of hpg.SCARKO testes (mean 8 +/- 6 per testis. No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice. Conclusion We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression.

Differential expression of Mediator complex subunit MED15 in testicular germ cell tumors.

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Klümper, Niklas; Syring, Isabella; Offermann, Anne; Shaikhibrahim, Zaki; Vogel, Wenzel; Müller, Stefan C; Ellinger, Jörg; Strauß, Arne; Radzun, Heinz Joachim; Ströbel, Philipp; Brägelmann, Johannes; Perner, Sven; Bremmer, Felix

2015-09-17

Testicular germ cell tumors (TGCT) are the most common cancer entities in young men with increasing incidence observed in the last decades. For therapeutic management it is important, that TGCT are divided into several histological subtypes. MED15 is part of the multiprotein Mediator complex which presents an integrative hub for transcriptional regulation and is known to be deregulated in several malignancies, such as prostate cancer and bladder cancer role, whereas the role of the Mediator complex in TGCT has not been investigated so far. Aim of the study was to investigate the implication of MED15 in TGCT development and its stratification into histological subtypes. Immunohistochemical staining (IHC) against Mediator complex subunit MED15 was conducted on a TGCT cohort containing tumor-free testis (n = 35), intratubular germ cell neoplasia unclassified (IGCNU, n = 14), seminomas (SEM, n = 107) and non-seminomatous germ cell tumors (NSGCT, n = 42), further subdivided into embryonic carcinomas (EC, n = 30), yolk sac tumors (YST, n = 5), chorionic carcinomas (CC, n = 5) and teratomas (TER, n = 2). Quantification of MED15 protein expression was performed through IHC followed by semi-quantitative image analysis using the Definiens software. In tumor-free seminiferous tubules, MED15 protein expression was absent or only low expressed in spermatogonia. Interestingly, the precursor lesions IGCNU exhibited heterogeneous but partly very strong MED15 expression. SEM weakly express the Mediator complex subunit MED15, whereas NSGCT and especially EC show significantly enhanced expression compared to tumor-free testis. In conclusion, MED15 is differentially expressed in tumor-free testis and TGCT. While MED15 is absent or low in tumor-free testis and SEM, NSGCT highly express MED15, hinting at the diagnostic potential of this marker to distinguish between SEM and NSGCT. Further, the precursor lesion IGCNU showed increased nuclear MED15

MicroRNAs in Testicular Cancer Diagnosis and Prognosis.

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Ling, Hui; Krassnig, Lisa; Bullock, Marc D; Pichler, Martin

2016-02-01

Testicular cancer processes a unique and clear miRNA expression signature. This differentiates testicular cancer from most other cancer types, which are usually more ambiguous when assigning miRNA patterns. As such, testicular cancer may represent a unique cancer type in which miRNAs find their use as biomarkers for cancer diagnosis and prognosis, with a potential to surpass the current available markers usually with low sensitivity. In this review, we present literature findings on miRNAs associated with testicular cancer, and discuss their potential diagnostic and prognostic values, as well as their potential as indicators of drug response in patients with testicular cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

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Ahmed, Maha A.E., E-mail: mahapharm@yahoo.com

2015-02-01

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level

Amelioration of nandrolone decanoate-induced testicular and sperm toxicity in rats by taurine: Effects on steroidogenesis, redox and inflammatory cascades, and intrinsic apoptotic pathway

International Nuclear Information System (INIS)

Ahmed, Maha A.E.

2015-01-01

The wide abuse of the anabolic steroid nandrolone decanoate by athletes and adolescents for enhancement of sporting performance and physical appearance may be associated with testicular toxicity and infertility. On the other hand, taurine; a free β-amino acid with remarkable antioxidant activity, is used in taurine-enriched beverages to boost the muscular power of athletes. Therefore, the purpose of this study was to investigate the mechanisms of the possible protective effects of taurine on nandrolone decanoate-induced testicular and sperm toxicity in rats. To achieve this aim, male Wistar rats were randomly distributed into four groups and administered either vehicle, nandrolone decanoate (10 mg/kg/week, I.M.), taurine (100 mg/kg/day, p.o.) or combination of taurine and nandrolone decanoate, for 8 successive weeks. Results of the present study showed that taurine reversed nandrolone decanoate-induced perturbations in sperm characteristics, normalized serum testosterone level, and restored the activities of the key steroidogenic enzymes; 3β-HSD, and 17β-HSD. Moreover, taurine prevented nandrolone decanoate-induced testicular toxicity and DNA damage by virtue of its antioxidant, anti-inflammatory, and anti-apoptotic effects. This was evidenced by taurine-induced modulation of testicular LDH-x activity, redox markers (MDA, NO, GSH contents, and SOD activity), inflammatory indices (TNF-α, ICAM-1 levels, and MMP-9 gene expression), intrinsic apoptotic pathway (cytochrome c gene expression and caspase-3 content), and oxidative DNA damage markers (8-OHdG level and comet assay). In conclusion, at the biochemical and histological levels, taurine attenuated nandrolone decanoate-induced poor sperm quality and testicular toxicity in rats. - Highlights: • Nandrolone decanoate (ND) disrupts sperm profile and steroidogenesis in rats. • ND upregulates gene expression of inflammatory and apoptotic markers. • Taurine normalizes sperm profile and serum testosterone level

Variation in the HFE gene is associated with the development of bleomycin-induced pulmonary toxicity in testicular cancer patients.

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van der Schoot, Gabriela G F; Westerink, Nico-Derk L; Lubberts, Sjoukje; Nuver, Janine; Zwart, Nynke; Walenkamp, Annemiek M E; Wempe, Johan B; Meijer, Coby; Gietema, Jourik A

2016-05-01

Bleomycin and cisplatin are of key importance in testicular cancer treatment. Known potential serious adverse effects are bleomycin-induced pulmonary toxicity (BIP) and cisplatin-induced renal toxicity. Iron handling may play a role in development of this toxicity. Carriage of allelic variants of the HFE gene induces altered iron metabolism and may contribute to toxicity. We investigated the association between two common allelic variants of the HFE gene, H63D and C282Y, with development of pulmonary and renal toxicity during and after treatment with bleomycin- and cisplatin-containing chemotherapy. In 369 testicular cancer patients treated with bleomycin and cisplatin at the University Medical Center Groningen between 1978 and 2006, H63D and/or C282Y genotypes were determined with an allelic discrimination assay. Data were collected on development of BIP, pulmonary function parameters, renal function, and survival. BIP developed more frequently in patients who were heterozygote (16 in 75, 21%) and homozygote (2 in 4, 50%) for the H63D variant, compared with those who had the HFE wild-type gene (31 in 278, 11%) (p = 0.012). Overall survival, testicular cancer-related survival, and change in renal function were not associated with the H63D variant. We observed an association between presence of one or both H63D alleles and development of BIP in testicular cancer patients treated with bleomycin combination chemotherapy. In patients heterozygote and homozygote for the H63D variant, BIP occurred more frequently compared with wild-type patients. When validated and confirmed, HFE H63D genotyping may be used to identify patients with increased risk for pulmonary bleomycin toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Testicular descent: INSL3, testosterone, genes and the intrauterine milieu.

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Bay, Katrine; Main, Katharina M; Toppari, Jorma; Skakkebæk, Niels E

2011-04-01

Complete testicular descent is a sign of, and a prerequisite for, normal testicular function in adult life. The process of testis descent is dependent on gubernacular growth and reorganization, which is regulated by the Leydig cell hormones insulin-like peptide 3 (INSL3) and testosterone. Investigation of the role of INSL3 and its receptor, relaxin-family peptide receptor 2 (RXFP2), has contributed substantially to our understanding of the hormonal control of testicular descent. Cryptorchidism is a common congenital malformation, which is seen in 2-9% of newborn boys, and confers an increased risk of infertility and testicular cancer in adulthood. Although some cases of isolated cryptorchidism in humans can be ascribed to known genetic defects, such as mutations in INSL3 or RXFP2, the cause of cryptorchidism remains unknown in most patients. Several animal and human studies are currently underway to test the hypothesis that in utero factors, including environmental and maternal lifestyle factors, may be involved in the etiology of cryptorchidism. Overall, the etiology of isolated cryptorchidism seems to be complex and multifactorial, involving both genetic and nongenetic components.

Effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and testicular steroidogenesis-related gene expression of their male kids in Taihang Black Goats.

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Shi, Lei; Song, Ruigao; Yao, Xiaolei; Duan, Yunli; Ren, Youshe; Zhang, Chunxiang; Yue, Wenbin; Lei, Fulin

2018-07-01

To investigate the effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and steroidogenesis-related gene expression in testis of their male kids, selected pregnant Taihang Black Goats were randomly allotted to four treatment groups. They were fed the basal gestation and lactation diets supplemented with 0 (control), 0.5, 2.0 and 4.0 mg of Se/kg DM. Thirty days after weaning, testes were collected from the kids. After the morphological development status of testis was examined, tissue samples were collected for analyzing testosterone concentration and histological parameters. Testosterone synthesis-related genes were detected using real-time PCR. Localization and quantification of androgen receptor (AR) in testis of goats were determined by immunohistochemical and western blot analysis. The results show that Se supplementation in the diet of dams led to higher (p kids. Excessive Se (4.0 mg/kg) can inhibit the development of testis by decreasing testicular weight and volume. The density of spermatogenic cells and Leydig cells in the Se treatment groups was significantly (p kids by modulating testosterone synthesis in goats. More attention should be given to the potential role of maternal nutrition in improving reproductive performance of their offspring. Copyright © 2018 Elsevier Inc. All rights reserved.

Testicular cancer

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... Germ cell tumor; Seminoma testicular cancer; Nonseminoma testicular cancer; Testicular neoplasm ... Philadelphia, PA: Elsevier Saunders; 2014:chap 86. National Cancer Institute. PDQ testicular cancer treatment. Updated February 17, 2016. www.cancer. ...

Duplication of SOX9 is not a common cause of 46,XX testicular or 46,XX ovotesticular DSD.

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Seeherunvong, Tossaporn; Ukarapong, Supamit; McElreavey, Kenneth; Berkovitz, Gary D; Perera, Erasmo M

2012-01-01

Translocation of the SRY gene to the paternal X chromosome is the explanation for testis development in the majority of subjects with 46,XX testicular disorder of sexual development (DSD). However, nearly all subjects with 46,XX ovotesticular DSD and up to one third of subjects with 46,XX testicular DSD lack SRY. SRY-independent expression of SOX9 has been implicated in the etiology of testis development in some individuals. We amplified microsatellite markers in the region of SOX9 from a cohort of 30 subjects with either 46,XX testicular or 46,XX ovotesticular DSD to detect SOX9 duplications. Duplication of the SOX9 region in 17q was not detected in any subject. Duplication in the region of 17q that contains SOX9 is not a common cause of testis development in subjects with SRY-negative 46,XX testicular or ovotesticular DSD.

Differential Gene Expression Profiling of Enriched Human Spermatogonia after Short- and Long-Term Culture

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Sabine Conrad

2014-01-01

Full Text Available This study aimed to provide a molecular signature for enriched adult human stem/progenitor spermatogonia during short-term (<2 weeks and long-term culture (up to more than 14 months in comparison to human testicular fibroblasts and human embryonic stem cells. Human spermatogonia were isolated by CD49f magnetic activated cell sorting and collagen−/laminin+ matrix binding from primary testis cultures obtained from ten adult men. For transcriptomic analysis, single spermatogonia-like cells were collected based on their morphology and dimensions using a micromanipulation system from the enriched germ cell cultures. Immunocytochemical, RT-PCR and microarray analyses revealed that the analyzed populations of cells were distinct at the molecular level. The germ- and pluripotency-associated genes and genes of differentiation/spermatogenesis pathway were highly expressed in enriched short-term cultured spermatogonia. After long-term culture, a proportion of cells retained and aggravated the “spermatogonial” gene expression profile with the expression of germ and pluripotency-associated genes, while in the majority of long-term cultured cells this molecular profile, typical for the differentiation pathway, was reduced and more genes related to the extracellular matrix production and attachment were expressed. The approach we provide here to study the molecular status of in vitro cultured spermatogonia may be important to optimize the culture conditions and to evaluate the germ cell plasticity in the future.

Autophagy-associated proteins BAG3 and p62 in testicular cancer.

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Bartsch, Georg; Jennewein, Lukas; Harter, Patrick N; Antonietti, Patrick; Blaheta, Roman A; Kvasnicka, Hans-Michael; Kögel, Donat; Haferkamp, Axel; Mittelbronn, Michel; Mani, Jens

2016-03-01

Testicular germ cell tumors (TGCT) represent the most common malignant tumor group in the age group of 20 to 40-years old men. The potentially curable effect of cytotoxic therapy in TGCT is mediated mainly by the induction of apoptosis. Autophagy has been discussed as an alternative mechanism of cell death but also of treatment resistance in various types of tumors. However, in TGCT the expression and role of core autophagy-associated factors is hitherto unknown. We designed the study in order to evaluate the potential role of autophagy-associated factors in the development and progression of testicular cancers. Eighty-four patients were assessed for autophagy (BAG3, p62) and apoptosis (cleaved caspase 3) markers using immunohistochemistry (IHC) on tissue micro- arrays. In addition, western blot analyses of frozen tissue of seminoma and non-seminoma were performed. Our findings show that BAG3 was significantly upregulated in seminoma as compared to non-seminoma but not to normal testicular tissue. No significant difference of p62 expression was detected between neoplastic and normal tissue or between seminoma and non-seminoma. BAG3 and p62 showed distinct loco‑regional expression patterns in normal and neoplastic human testicular tissues. In contrast to the autophagic markers, apoptosis rate was significantly higher in testicular tumors as compared to normal testicular tissue, but not between different TGCT subtypes. The present study, for the first time, examined the expression of central autophagy proteins BAG3 and p62 in testicular cancer. Our findings imply that in general apoptosis but not autophagy induction differs between normal and neoplastic testis tissue.

Testicular Cancer Screening

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... undescended testicle) is a risk factor for testicular cancer. Testicular cancer is a disease in which malignant (cancer) ... Testicular Cancer Treatment for more information about testicular cancer. Testicular cancer is the most common cancer in men ...

Reconstruction of mouse testicular cellular microenvironments in long-term seminiferous tubule culture.

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Juho-Antti Mäkelä

Full Text Available Research on spermatogonia is hampered by complex architecture of the seminiferous tubule, poor viability of testicular tissue ex vivo and lack of physiologically relevant long-term culture systems. Therefore there is a need for an in vitro model that would enable long term survival and propagation of spermatogonia. We aimed at the most simplified approach to enable all different cell types within the seminiferous tubules to contribute to the creation of a niche for spermatogonia. In the present study we describe the establishment of a co-culture of mouse testicular cells that is based on proliferative and migratory activity of seminiferous tubule cells and does not involve separation, purification or differential plating of individual cell populations. The co-culture is composed of the constituents of testicular stem cell niche: Sertoli cells [identified by expression of Wilm's tumour antigen 1 (WT1 and secretion of glial cell line-derived neurotrophic factor, GDNF], peritubular myoid cells (expressing alpha smooth muscle actin, αSMA and spermatogonia [expressing MAGE-B4, PLZF (promyelocytic leukaemia zinc finger, LIN28, Gpr125 (G protein-coupled receptor 125, CD9, c-Kit and Nanog], and can be maintained for at least five weeks. GDNF was found in the medium at a sufficient concentration to support proliferating spermatogonial stem cells (SSCs that were able to start spermatogenic differentiation after transplantation to an experimentally sterile recipient testis. Gdnf mRNA levels were elevated by follicle-stimulating hormone (FSH which shows that the Sertoli cells in the co-culture respond to physiological stimuli. After approximately 2-4 weeks of culture a spontaneous formation of cord-like structures was monitored. These structures can be more than 10 mm in length and branch. They are formed by peritubular myoid cells, Sertoli cells, fibroblasts and spermatogonia as assessed by gene expression profiling. In conclusion, we have managed to

Expression of the glycolipid globotriaosylceramide (Gb3) in testicular carcinoma in situ

DEFF Research Database (Denmark)

Kang, J L; Rajpert-De Meyts, E; Wiels, J

1995-01-01

of the globo-series core-structure, globotriaosylceramide (Gb3) was investigated in the preinvasive stage of testicular germ cell tumours, carcinoma in situ (CIS). Seventeen tissue specimens with CIS and 12 samples of overt testicular tumours were immunostained with anti-Gb3 monoclonal antibody 38...

Testicular microlithiasis and testicular cancer: review of the literature.

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Pedersen, Malene Roland; Rafaelsen, Søren Rafael; Møller, Henrik; Vedsted, Peter; Osther, Palle Jörn

2016-07-01

To perform a systematic literature review to assess whether the occurrence of testicular microlithiasis (TML) in conjunction with other risk factors is associated with testicular cancer. A systematic literature search was performed of original articles in English published 1998 to 2015. Relevant studies were selected by reading the title and abstract by two of the authors. Studies were included if TML was diagnosed by ultrasonography and a risk condition was reported. Studies were only eligible if the particular risk condition was reported in more than one article. In total, 282 abstracts in were identified. Based on title and abstract the eligibility was assessed and 31 studies were included. Five conditions in relation to TML and testicular cancer emerged: Down syndrome, McCune-Albright syndrome, cryptorchidism, infertility and familial disposition of testicular cancer. Data support the conclusion that TML is not an independent risk factor for testicular cancer but associated with testicular cancer through other conditions. In male infertility, TML appears to be related to an increased risk of testicular cancer possibly as part of a testicular dysgenesis syndrome.

Genetic variation in hormone metabolizing genes and risk of testicular germ cell tumors.

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Figueroa, Jonine D; Sakoda, Lori C; Graubard, Barry I; Chanock, Stephen; Rubertone, Mark V; Erickson, R Loren; McGlynn, Katherine A

2008-11-01

Testicular germ cell tumors (TGCT) that arise in young men are composed of two histologic types, seminomas and nonseminomas. Risk patterns for the two types appear to be similar and may be related to either endogenous or exogenous hormonal exposures in utero. Why similar risk patterns would result in different histologic types is unclear, but could be related to varying genetic susceptibility profiles. Genetic variation in hormone metabolizing genes could potentially modify hormonal exposures, and thereby affect which histologic type a man develops. To examine this hypothesis, 33 single nucleotide polymorphisms (SNPs) in four hormone metabolism candidate genes (CYP1A1, CYP17A1, HSD17B1, HSD17B4) and the androgen receptor gene (AR) were genotyped. Associations with TGCT were evaluated among 577 TGCT cases (254 seminoma, 323 nonseminoma) and 707 controls from the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study. There were no significant associations with TGCT overall based on a test using an additive model. However, compared to homozygotes of the most common allele, two nonredundant SNPs in CYP1A1 were inversely associated with nonseminoma: CYP1A1 promoter SNP rs4886605 OR = 0.75 (95% CI = 0.54-1.04) among the heterozygotes and OR = 0.37, 95% CI = 0.12-1.11 among the homozygotes with a p-value for trend = 0.02; rs2606345 intron 1 SNP, OR = 0.69 (95% CI = 0.51-0.93) among heterozygotes and OR = 0.70 (95% CI = 0.42-1.17) among homozygotes, with a p-value for trend = 0.02. Caution in interpretation is warranted until findings are replicated in other studies; however, the results suggest that genetic variation in CYP1A1 may be associated with nonseminoma.

Altered expression profile of glycolytic enzymes during testicular ischemia reperfusion injury is associated with the p53/TIGAR pathway: effect of fructose 1,6-diphosphate

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May Al-Maghrebi

2016-07-01

Full Text Available Background. Testicular ischemia reperfusion injury (tIRI is considered the mechanism underlying the pathology of testicular torsion and detorsion. Left untreated, tIRI can induce testis dysfunction, damage to spermatogenesis and possible infertility. In this study, we aimed to assess the activities and expression of glycolytic enzymes (GEs in the testis and their possible modulation during tIRI. The effect of fructose 1,6-diphosphate (FDP, a glycolytic intermediate, on tIRI was also investigated. Methods. Male Sprague-Dawley rats were divided into three groups: sham, unilateral tIRI, and tIRI + FDP (2 mg/kg. tIRI was induced by occlusion of the testicular artery for 1 h followed by 4 h of reperfusion. FDP was injected peritoneally 30 min prior to reperfusion. Histological and biochemical analyses were used to assess damage to spermatogenesis, activities of major GEs, and energy and oxidative stress markers. The relative mRNA expression of GEs was evaluated by real-time PCR. ELISA and immunohistochemistry were used to evaluate the expression of p53 and TP53-induced glycolysis and apoptosis regulator (TIGAR. Results. Histological analysis revealed tIRI-induced spermatogenic damage as represented by a significant decrease in the Johnsen biopsy score. In addition, tIRI reduced the activities of hexokinase 1, phosphofructokinase-1, glyceraldehyde 3-phosphate dehydrogenase, and lactate dehydrogenase C. However, mRNA expression downregulation was detected only for hexokinase 1, phosphoglycerate kinase 2, and lactate dehydrogenase C. ATP and NADPH depletion was also induced by tIRI and was accompanied by an increased Malondialdehyde concentration, reduced glutathione level, and reduced superoxide dismutase and catalase enzyme activities. The immunoexpression of p53 and TIGAR was markedly increased after tIRI. The above tIRI-induced alterations were attenuated by FDP treatment. Discussion. Our findings indicate that tIRI-induced spermatogenic damage is

Gene expression profiles in testis of pigs with extreme high and low levels of androstenone

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Bendixen Christian

2007-11-01

Full Text Available Abstract Background: Boar taint is a major obstacle when using uncastrated male pigs for swine production. One of the main compounds causing this taint is androstenone, a pheromone produced in porcine testis. Here we use microarrays to study the expression of thousands of genes simultaneously in testis of high and low androstenone boars. The study allows identification of genes and pathways associated with elevated androstenone levels, which is essential for recognising potential molecular markers for breeding purposes. Results: Testicular tissue was collected from 60 boars, 30 with extreme high and 30 with extreme low levels of androstenone, from each of the two breeds Duroc and Norwegian Landrace. The samples were hybridised to porcine arrays containing 26,877 cDNA clones, detecting 563 and 160 genes that were differentially expressed (p Conclusion: This study contributes to the understanding of the complex genetic system controlling and responding to androstenone levels in pig testis. The identification of new pathways and genes involved in the biosynthesis and metabolism of androstenone is an important first step towards finding molecular markers to reduce boar taint.

Teaching about Testicular Cancer and Testicular Self-examination.

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Marty, Phillip J.; McDermott, Robert J.

1983-01-01

Because testicular cancer is one of the most commonly diagnosed cancers in young men, it is important that they become informed about it. This paper reviews the pathology and epidemiology of testicular cancer, the technique of testicular self-examination, and some suggestions for teaching about this subject. (Authors/JMK)

Sulforaphane Prevents Testicular Damage in Kunming Mice Exposed to Cadmium via Activation of Nrf2/ARE Signaling Pathways

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Shu-Hua Yang

2016-10-01

Full Text Available Sulforaphane (SFN is a natural and highly effective antioxidant. Studies suggest that SFN protects cells and tissues against cadmium (Cd toxicity. This study investigated the protective effect of SFN against oxidative damage in the testes of Kunming mice exposed to cadmium, and explored the possible molecular mechanisms involved. Cadmium greatly reduced the serum testosterone levels in mice, reduced sperm motility, total sperm count, and increased the sperm deformity rate. Cadmium also reduces superoxide dismutase (T-SOD and glutathione (GSH levels and increases malondialdehyde (MDA concentrations. SFN intervention improved sperm quality, serum testosterone, and antioxidant levels. Both mRNA and protein expression of mouse testicular nuclear factor-erythroid 2-related factor 2 (Nrf2 was reduced in cadmium-treated group. Furthermore, the downstream genes of Nrf2, glutathione peroxidase (GSH-Px, γ-glutamyl cysteine synthetase (γ-GCS, heme oxygenase-1 (HO-1, and NAD(PH:quinone oxidoreductase-1 (NQO1 were also decreased in cadmium-treated group. SFN intervention increases the expression of these genes. Sulforaphane prevents cadmium-induced testicular damage, probably via activation of Nrf2/ARE signaling.

Intra-Abdominal Testicular Seminoma in a Woman with Testicular Feminization Syndrome

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Darshana D. Rasalkar

2011-01-01

Full Text Available We report a case of intra-abdominal testicular tumor in a 36-year-old married lady presenting with chief complaints of primary amenorrhea. The patient was later diagnosed with testicular feminization syndrome, a form of male pseudohermaphroditism. This testicular tumor was histologically proven as seminoma. Due to rarity, imaging findings in patients with testicular feminization syndrome and intraabdominal testicular tumor have been poorly documented. So far, only one case report had described the combined role of CT and MR imaging in intraabdominal testicular sex-cord stromal tumor. To our knowledge, this case is first to document USG and MR imaging in addition to MR spectroscopy features in intraabdominal testicular seminoma.

Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

2017-01-01

Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

Testicular Microlithiasis

DEFF Research Database (Denmark)

Pedersen, Malene Roland Vils; Osther, Palle Jørn Sloth; Sørensen, Flemming Brandt

2016-01-01

factors (testicular atrophy (N=1) and previous testicular cancer (N=4)), but no cases of testicular malignancy were found in the follow-up period. Conclusion: The low patient compliance conflicts with the ESUR Scrotal Imaging Subcommittee guidelines that recommend scrotal US follow-up annually for TML...

Effect of zearalenone on reproductive parameters and expression of selected testicular genes in mice

Czech Academy of Sciences Publication Activity Database

Žatecká, Eva; Děd, Lukáš; Elzeinová, Fatima; Kubátová, Alena; Dorosh, Andriy; Margaryan, Hasmik; Dostálová, Pavla; Korenková, Vlasta; Hošková, K.; Pěknicová, Jana

2014-01-01

Roč. 45, june (2014), s. 20-30 ISSN 0890-6238 R&D Projects: GA ČR(CZ) GAP503/12/1834; GA MŠk(CZ) ED1.1.00/02.0109 Institutional research plan: CEZ:AV0Z50520701 Institutional support: RVO:86652036 Keywords : zearalenone * fertility * reproductive parameters in male mice * spermatogenesis * gene expression * qPCR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.227, year: 2014

Sexually Dimorphic Expression of Secreted Frizzled-Related (SFRP) Genes in the Developing Mouse Müllerian Duct

Science.gov (United States)

COX, SAM; SMITH, LEE; BOGANI, DEBORA; CHEESEMAN, MICHAEL; SIGGERS, PAM; GREENFIELD, ANDY

2007-01-01

In developing male embryos, the female reproductive tract primordia (Müllerian ducts) regress due to the production of testicular anti-Müllerian hormone (AMH). Because of the association between secreted frizzled-related proteins (SFRPs) and apoptosis, their reported developmental expression patterns and the role of WNT signaling in female reproductive tract development, we examined expression of Sfrp2 and Sfrp5 during development of the Müllerian duct in male (XY) and female (XX) mouse embryos. We show that expression of both Sfrp2 and Sfrp5 is dynamic and sexually dimorphic. In addition, the male-specific expression observed for both genes prior to the onset of regression is absent in mutant male embryos that fail to undergo Müllerian duct regression. We identified ENU-induced point mutations in Sfrp5 and Sfrp2 that are predicted to severely disrupt the function of these genes. Male embryos and adults homozygous for these mutations, both individually and in combination, are viable and apparently fertile with no overt abnormalities of reproductive tract development. PMID:16700072

Gene expression and gene therapy imaging

International Nuclear Information System (INIS)

Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

2007-01-01

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

Carcinoma in situ testis, the progenitor of testicular germ cell tumours

DEFF Research Database (Denmark)

Hoei-Hansen, C E; Rajpert-De Meyts, E; Daugaard, G

2005-01-01

Testicular germ cell tumours (TGCT), including seminomas, embryonal carcinomas, teratomas and yolk sac tumours, have a common precursor, the carcinoma in situ (CIS) cell. Recent gene expression studies displaying close similarity of CIS cells to embryonic stem cells support the longstanding theory...... should be made to obtain diagnosis at the CIS stage, as intervention is possible before an invasive tumour develops, thus reducing the necessity for intensive therapy. CIS may be suspected in patients with an assumed extragonadal GCT or cryptorchidism, and in intersex patients and selected cases...

Association of the polymorphism of the CAG repeat in the mitochondrial DNA polymerase gamma gene (POLG) with testicular germ-cell cancer

DEFF Research Database (Denmark)

Blomberg Jensen, M; Leffers, H; Petersen, J H

2008-01-01

BACKGROUND: A possible association between the polymorphic CAG repeat in the DNA polymerase gamma (POLG) gene and the risk of testicular germ-cell tumours (TGCT) was investigated in this study. The hypothesis was prompted by an earlier preliminary study proposing an association of the absence...

Gene expression

International Nuclear Information System (INIS)

Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

1983-01-01

We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

Epigenetic: a molecular link between testicular cancer and environmental exposures?

Directory of Open Access Journals (Sweden)

Aurelie eVega

2012-11-01

Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Lack of effect on rat testicular organogenesis after in utero exposure to 3-monochloropropane-1,2-diol (3-MCPD).

Science.gov (United States)

El Ramy, Rosy; Ould Elhkim, Mostafa; Poul, Martine; Forest, Maguelone G; Leduque, Patrick; Le Magueresse-Battistoni, Brigitte

2006-10-01

3-Monochloropropane-1,2-diol (3-MCPD) is a food-born contaminant known to display toxic effects on male reproduction, producing infertility in rats and humans. Using the rat as a model, we investigated whether or not testicular organogenesis, which, in the rat species, occurs during the second half of gestation, was at particular risk regarding 3-MCPD toxicity. Pregnant rats were given daily doses of 5, 10 or 25 mg/kg BW of 3-MCPD from days 11.5-18.5 postcoitum (dpc). On 19.5 dpc, testes were removed from fetuses for histological examination and testosterone analysis. Eight genes were selected among the differentiation markers of testicular cell lineages, and their expression was studied by RT-PCR. The levels of 3-MCPD and its main metabolite, beta-chlorolactic acid, were assayed in fetal tissues and dam plasma. Our results show a statistically significant decrease in the mean body weight gain of pregnant rats treated with 10 and 25 mg/kg BW of 3-MCPD. Fetal testes exposed to 3-MCPD exhibited normal histology and produced testosterone at levels that were similar to controls. In addition, 3-MCPD did not alter gene expression in the fetal testes. This lack of effect occurred under conditions where 3-MCPD and beta-chlorolactic acid were found to readily cross the placental barrier and diffuse throughout the fetal tissues. Our findings indicate that 3-MCPD has minimal effect on rat testicular organogenesis.

Application of benchmark dose modeling to protein expression data in the development and analysis of mode of action/adverse outcome pathways for testicular toxicity.

Science.gov (United States)

Chepelev, Nikolai L; Meek, M E Bette; Yauk, Carole Lyn

2014-11-01

Reliable quantification of gene and protein expression has potential to contribute significantly to the characterization of hypothesized modes of action (MOA) or adverse outcome pathways for critical effects of toxicants. Quantitative analysis of gene expression by benchmark dose (BMD) modeling has been facilitated by the development of effective software tools. In contrast, protein expression is still generally quantified by a less robust effect level (no or lowest [adverse] effect levels) approach, which minimizes its potential utility in the consideration of dose-response and temporal concordance for key events in hypothesized MOAs. BMD modeling is applied here to toxicological data on testicular toxicity to investigate its potential utility in analyzing protein expression relevant to the proposed MOA to inform human health risk assessment. The results illustrate how the BMD analysis of protein expression in animal tissues in response to toxicant exposure: (1) complements other toxicity data, and (2) contributes to consideration of the empirical concordance of dose-response relationships, as part of the weight of evidence for hypothesized MOAs to facilitate consideration and application in regulatory risk assessment. Lack of BMD analysis in proteomics has likely limited its use for these purposes. This paper illustrates the added value of BMD modeling to support and strengthen hypothetical MOAs as a basis to facilitate the translation and uptake of the results of proteomic research into risk assessment. Copyright © 2014 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology © 2014 John Wiley & Sons, Ltd.

Prospectively Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort.

Science.gov (United States)

Pathak, Anand; Adams, Charleen D; Loud, Jennifer T; Nichols, Kathryn; Stewart, Douglas R; Greene, Mark H

2015-10-01

Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR = 11.9; 95% CI, 5.1-23.4; excess absolute risk = 7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR = 13.4; 95% CI, 1.6-48.6). Our data are the first to indicate that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. ©2015 American Association for Cancer Research.

Prospectively-Identified Incident Testicular Cancer Risk in a Familial Testicular Cancer Cohort

Science.gov (United States)

Pathak, Anand; Adams, Charleen D.; Loud, Jennifer T.; Nichols, Kathryn; Stewart, Douglas R.; Greene, Mark H.

2015-01-01

Background Human testicular germ cell tumors (TGCT) have a strong genetic component and a high familial relative risk. However, linkage analyses have not identified a rare, highly-penetrant familial TGCT (FTGCT) susceptibility locus. Currently, multiple low-penetrance genes are hypothesized to underlie the familial multiple-case phenotype. The observation that two is the most common number of affected individuals per family presents an impediment to FTGCT gene discovery. Clinically, the prospective TGCT risk in the multiple-case family context is unknown. Methods We performed a prospective analysis of TGCT incidence in a cohort of multiple-affected-person families and sporadic-bilateral-case families; 1,260 men from 140 families (10,207 person-years of follow-up) met our inclusion criteria. Age-, gender-, and calendar time-specific standardized incidence ratios (SIR) for TGCT relative to the general population were calculated using SEER*Stat. Results Eight incident TGCTs occurred during prospective FTGCT cohort follow-up (versus 0.67 expected; SIR=11.9; 95% confidence interval [CI]=5.1–23.4; excess absolute risk=7.2/10,000). We demonstrate that the incidence rate of TGCT is greater among bloodline male relatives from multiple-case testicular cancer families than that expected in the general population, a pattern characteristic of adult-onset Mendelian cancer susceptibility disorders. Two of these incident TGCTs occurred in relatives of sporadic-bilateral cases (0.15 expected; SIR=13.4; 95%CI=1.6–48.6). Conclusions Our data are the first indicating that despite relatively low numbers of affected individuals per family, members of both multiple-affected-person FTGCT families and sporadic-bilateral TGCT families comprise high-risk groups for incident testicular cancer. Impact Men at high TGCT risk might benefit from tailored risk stratification and surveillance strategies. PMID:26265202

Recovery of testicular blood flow following ligation of testicular vessels

International Nuclear Information System (INIS)

Pascual, J.A.; Villanueva-Meyer, J.; Salido, E.; Ehrlich, R.M.; Mena, I.; Rajfer, J.

1989-01-01

To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133-xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach

Neighboring Genes Show Correlated Evolution in Gene Expression

Science.gov (United States)

Ghanbarian, Avazeh T.; Hurst, Laurence D.

2015-01-01

When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

Gene Expression Commons: an open platform for absolute gene expression profiling.

Directory of Open Access Journals (Sweden)

Jun Seita

Full Text Available Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000 of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/ which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

International Nuclear Information System (INIS)

Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi; Nishimura, Kazuo; Jo, Yoshimasa; Nagai, Atsushi; Okuyama, Akihiko; Nonomura, Norio

2010-01-01

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

SERPINE2 is a possible candidate promotor for lymph node metastasis in testicular cancer

Energy Technology Data Exchange (ETDEWEB)

Nagahara, Akira; Nakayama, Masashi; Oka, Daizo; Tsuchiya, Mutsumi; Kawashima, Atsunari; Mukai, Masatoshi; Nakai, Yasutomo; Takayama, Hitoshi [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nishimura, Kazuo [Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamachi, Higashinari-ku, Osaka, 537-8511 (Japan); Jo, Yoshimasa; Nagai, Atsushi [Department of Urology, Kawasaki Medical University, 577 Matsushima, Kurashiki-City, Okayama 701-0192 (Japan); Okuyama, Akihiko [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan); Nonomura, Norio, E-mail: nono@uro.med.osaka-u.ac.jp [Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-City, Osaka 565-0871 (Japan)

2010-01-22

Testicular germ cell tumors (TGCTs) commonly metastasize to the lymph node or lung. However, it remains unclear which genes are associated with TGCT metastasis. The aim of this study was to identify gene(s) that promoted human TGCT metastasis. We intraperitoneally administered conditioned medium (CM) from JKT-1, a cell-line from a human testicular seminoma, or JKT-HM, a JKT-1 cell sub-line with high metastatic potential, into mice with JKT-1 xenografts. Administration of CM from JKT-HM significantly promoted lymph node metastasis. A cDNA microarray analysis showed that JKT-HM cells highly expressed the Serpine peptidase inhibitor, clade E, member 2 (SERPINE2), which encodes a secreted protein. Administration of CM from SERPINE2-silenced JKT-HM cells inhibited lymph node metastasis in the xenograft model, compared with administration of CM from JKT-HM cells. There was no significant difference in xenograft volume. Moreover, administration of CM from SERPINE2-over-expressing JKT-1 was likely to promote lymph node metastasis in the xenograft model. There was no difference in the in vitro proliferation or migration of JKT-1 cells cultured with CM from JKT-HM cells, compared to that with CM from JKT-1. There was no promotion of proliferation or lymphangiogenesis in the xenografts, as measured by Ki-67 and LYVE-1 immunohistochemistry, respectively. Although we could not clarify how SERPINE2 promoted lymph node metastasis, it may be a promoter in the development of lymph node metastasis in the human seminoma cells in a mouse xenograft model.

The Y-located gonadoblastoma gene TSPY amplifies its own expression through a positive feedback loop in prostate cancer cells

Energy Technology Data Exchange (ETDEWEB)

Kido, Tatsuo; Lau, Yun-Fai Chris, E-mail: Chris.Lau@UCSF.edu

2014-03-28

Highlights: • Y-encoded proto-oncoprotein TSPY amplifies its expression level via a positive feedback loop. • TSPY binds to the chromatin/DNA at exon 1 of TSPY gene. • TSPY enhances the gene expression in a TSPY exon 1 sequence dependent manner. • The conserved SET/NAP-domain is essential for TSPY transactivation. • Insights on probable mechanisms on TSPY exacerbation on cancer development in men. - Abstract: The testis-specific protein Y-encoded (TSPY) is a repetitive gene located on the gonadoblastoma region of the Y chromosome, and has been considered to be the putative gene for this oncogenic locus on the male-only chromosome. It is expressed in spermatogonial cells and spermatocytes in normal human testis, but abundantly in gonadoblastoma, testicular germ cell tumors and a variety of somatic cancers, including melanoma, hepatocellular carcinoma and prostate cancer. Various studies suggest that TSPY accelerates cell proliferation and growth, and promotes tumorigenesis. In this report, we show that TSPY could bind directly to the chromatin/DNA at exon 1 of its own gene, and greatly enhance the transcriptional activities of the endogenous gene in the LNCaP prostate cancer cells. Domain mapping analyses of TSPY have localized the critical and sufficient domain to the SET/NAP-domain. These results suggest that TSPY could efficiently amplify its expression and oncogenic functions through a positive feedback loop, and contribute to the overall tumorigenic processes when it is expressed in various human cancers.

Variations in testosterone pathway genes and susceptibility to testicular cancer in Norwegian men.

Science.gov (United States)

Kristiansen, W; Aschim, E L; Andersen, J M; Witczak, O; Fosså, S D; Haugen, T B

2012-12-01

Imbalance between the oestrogen and androgen levels in utero is hypothesized to influence testicular cancer (TC) risk. Thus, variation in genes involved in the action of sex hormones may contribute to variability of an individual's susceptibility to TC. Mutations in testosterone pathway genes may alter the level of testosterone in vivo and hypothetically the risk of developing TC. Luteinizing hormone receptor (LHR), 5α-reductase II (SRD5A2) and androgen receptor (AR) are key elements in androgen action. A case-control study comprising 651 TC cases and 313 controls in a Norwegian population was conducted for investigation of polymorphisms in the LHR, SRD5A and AR genes and their possible association with TC. A statistical significant difference was observed in patients being heterozygous for the LHR Asn312Ser polymorphism when comparing genotypes between all TC cases and controls (OR = 0.66, 95% CI = 0.48-0.89, p(adj) = 0.049). No statistically significant difference between the histological subtypes seminoma and non-seminoma was observed. Our results may suggest a possible association between genetic variation in the LHR gene and the risk of developing TC. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

Effect of neonatal or adult heat acclimation on plasma fT3 level, testicular thyroid receptors expression in male rats and testicular steroidogenesis in vitro in response to triiodothyronine treatment.

Science.gov (United States)

Kurowicka, B; Chrusciel, M; Zmijewska, A; Kotwica, G

2016-01-01

This study aimed to evaluate the effect of heat acclimation of neonatal and adult rats on their testes response to in vitro treatment with triiodothyronine (T3). Four groups of rats were housed from birth as: 1) control (CR) at 20°C for 90 days, 2) neonatal heat-acclimated (NHA) at 34°C for 90 days, 3) adult heat-acclimated (AHA) at 20°C for 45 days followed by 45 days at 34°C and 4) de-acclimated (DA) at 34°C for 45 days followed by 45 days at 20°C. Blood plasma and both testes were harvested from 90-day old rats. Testicular slices were then submitted to in vitro treatment with T3 (100 ng/ml) for 8 h. Plasma fT3 level was lower in AHA, NHA and DA groups than in CR group. Basal thyroid hormone receptor α1 (Thra1) expression was higher in testes of NHA and DA and β1 receptor (Thrb1) in DA rats vs. other groups. In the in vitro experiment, T3: 1) decreased Thra1 expression in all groups and Thrb1 in DA group, 2) increased Star expression in CR, NHA and DA groups, and Hsd17b3 expression in NHA group, 3) decreased the expression of Cyp11a1 in NHA and DA groups, and Cyp19a1 in all the groups, 4) did not affect the activity of steroidogenic enzymes and steroid secretion (A4, T, E2) in all the groups. These results indicate, that heat acclimation of rats, depending on their age, mainly affects the testicular expression of steroidogenic enzymes in response to short-lasting treatment with T3.

Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

Energy Technology Data Exchange (ETDEWEB)

Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

2014-09-01

Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

Identifying functional cancer-specific miRNA-mRNA interactions in testicular germ cell tumor.

Science.gov (United States)

Sedaghat, Nafiseh; Fathy, Mahmood; Modarressi, Mohammad Hossein; Shojaie, Ali

2016-09-07

Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Testicular steroidogenesis is not altered by 137 cesium Chernobyl fallout, following in utero or post-natal chronic exposure.

Science.gov (United States)

Grignard, Elise; Guéguen, Yann; Grison, Stéphane; Dublineau, Isabelle; Gourmelon, Patrick; Souidi, Maâmar

2010-05-01

The testis is especially sensitive to pollutants, including radionuclides. Following the Chernobyl nuclear power plant accident, several of these radionuclides were emitted and spread in the environment. Subsequently, children presented some disruptions of the endocrine system. To determine whether these disruptions were due to 137 cesium ((137)Cs) exposure, the effects of chronic contamination with low doses of (137)Cs in utero or from birth on testicular steroidogenesis in rats were studied. Contamination was continued for 9 months. No modification was observed in circulating level of hormones (17beta-estradiol, testosterone, follicle-stimulating hormone, luteinizing hormone) following in utero or post-natal contamination. Expression of several genes involved in testicular steroidogenesis was affected (cyp19a1, fxr, sf-1), without modification of protein expression or activity. Our results suggest that growing organisms may be affected at the molecular level by (137)Cs contamination at this post-accidental dose. Copyright 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Cancer in first-degree relatives and risk of testicular cancer in Denmark

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Nordsborg, Rikke Baastrup; Meliker, Jaymie R.; Wohlfahrt, Jan; Melbye, Mads; Raaschou-Nielsen, Ole

2011-01-01

Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. 6594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyse whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio (RR) for testicular cancer was 4.63 (95% CI: 2.41–8.87) when a father, 8.30(95% CI: 3.81–18.10) when a brother and 5.23 (95% CI: 1.35–20.26) when a son had testicular cancer compared with no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial Non-Hodgkin lymphoma and oesophageal cancer were associated with testicular cancer; however these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine. PMID:21207375

Two males with SRY-positive 46,XX testicular disorder of sex development.

Science.gov (United States)

Gunes, Sezgin; Asci, Ramazan; Okten, Gülsen; Atac, Fatih; Onat, Onur E; Ogur, Gonul; Aydin, Oguz; Ozcelik, Tayfun; Bagci, Hasan

2013-02-01

The 46,XX testicular disorder of sex development (46,XX testicular DSD) is a rare phenotype associated with disorder of the sex chromosomes. We describe the clinical, molecular, and cytogenetic findings of a 16- and a 30-year-old male patient with sex-determining region Y (SRY)-positive 46,XX testicular DSD. Chromosomal analysis revealed 46,XX karyotype. Fluorescence in situ hybridization (FISH) showed the SRY region translocated to the short arm of the X chromosome. The presence of the SRY gene was also confirmed by polymerase chain reaction (PCR). The X chromosome inactivation (XCI) assay showed that both patients have a random pattern of X chromosome inactivation. This report compares the symptoms and features of the SRY-positive 46,XX testicular DSD patients.

Imaging gene expression in gene therapy

International Nuclear Information System (INIS)

Wiebe, Leonard I.

1997-01-01

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

Testicular cancer and male infertility.

Science.gov (United States)

Paduch, Darius A

2006-11-01

Testicular cancer and infertility affect a similar age group of patients and have common biologic, epidemiologic, and environmental backgrounds. In this review, we provide current literature on links between infertility and testicular cancer, and new developments in the management of testicular cancer aimed at improving quality of life in men with testicular cancer. In-utero environmental exposure to endocrine disruptors modulates the genetically determined fate of primitive gonad and results in testicular dysgenesis syndrome, which may result in infertility and testicular cancer. Excellent response of testicular cancer to radiation and chemotherapy results in over 90% of survival and quality of life--fertility and sexual function--is of significant concern to patients and clinicians. The testicular-sparing management of testicular masses emerges as a sound alternative to radical orchiectomy and allows for preservation of spermatogenesis and hormonal function, and at the same time achieving similar survival rates. Secondary malignancies, pulmonary, and cardiovascular complications are recognized as late complications of treatment for testicular cancer. Better understanding of common mechanisms involved in infertility and testicular cancer, and scientifically driven evidence-based treatment options should improve quality of life in young men faced with this potentially life-threatening disease.

Myeloid cell leukemia-1 (Mc1-1 is a candidate target gene of hypoxia-inducible factor-1 (HIF-1 in the testis

Directory of Open Access Journals (Sweden)

Palladino Michael A

2012-12-01

Full Text Available Abstract Background Spermatic cord torsion can lead to testis ischemia (I and subsequent ischemia-reperfusion (I/R causing germ cell-specific apoptosis. Previously, we demonstrated that the hypoxia-inducible factor-1 (HIF-1 transcription factor, a key regulator of physiological responses to hypoxia, is abundant in Leydig cells in normoxic and ischemic testes. We hypothesize that testicular HIF-1 activates the expression of antiapoptotic target genes to protect Leydig cells from apoptosis. In silico analysis of testis genes containing a consensus hypoxia response element (HRE, 5’-RCGTG-3’ identified myeloid cell leukemia-1 (Mcl-1 as a potential HIF-1 target gene. The purpose of this study was to determine whether HIF-1 shows DNA-binding activity in normoxic and ischemic testes and whether Mcl-1 is a target gene of testicular HIF-1. Methods The testicular HIF-1 DNA-binding capacity was analyzed in vitro using a quantitative enzyme-linked immunosorbent assay (ELISA and electrophoretic mobility shift assays (EMSA. MCL-1 protein expression was evaluated by immunoblot analysis and immunohistochemistry. The binding of testicular HIF-1 to the Mcl-1 gene was examined via chromatin immunoprecipitation (ChIP analysis. Results The ELISA and EMSA assays demonstrated that testicular HIF-1 from normoxic and ischemic testes binds DNA equally strongly, suggesting physiological roles for HIF-1 in the normoxic testis, unlike most tissues in which HIF-1 is degraded under normoxic conditions and is only activated by hypoxia. MCL-1 protein was determined to be abundant in both normoxic and ischemic testes and expressed in Leydig cells. In a pattern identical to that of HIF-1 expression, the steady-state levels of MCL-1 were not significantly affected by I or I/R and MCL-1 co-localized with HIF-1α in Leydig cells. Chromatin immunoprecipitation (ChIP analysis using a HIF-1 antibody revealed sequences enriched for the Mcl-1 promoter. Conclusions The results

Mechanisms of Heshouwuyin in regulating apoptosis of testicular cells in aging rats through mitochondrial pathway.

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Chen, Jingbo; Wang, Yujuan; Hui, Chenhong; Xi, Yao; Liu, Xiang; Qi, Feng; Liu, Haokun; Wang, Zhenshan; Niu, Siyun

2016-09-01

Polygonum multiflorum has important effects on anti-aging and immunity enhancement. Many traditional Chinese medicine preparations based on Polygonum multiflorum are widely used for the clinical prevention and treatment of aging. However the mechanisms of these herb mixtures are often unknown. This study investigates the effect of Heshouwuyin, a Chinese herbal compound for invigorating the kidney, on the regulation of testicular cells apoptosis in aging rats. In this study, 18-month-old Wistar rats served as a model of natural aging and 12-month-old rats served as a young control group. Heshouwuyin group 1 and group 2 were comprised 18-month-old rats given Heshouwuyin intragastrically for 60 days and 30 days respectively. Then testes of the young control group were isolated in the age of 12 months, the other three groups were in the age of 18 months. TUNEL assay showed that the rate of testicular cell apoptosis was obviously higher and Flow cytometry analysis showed that the rate of cell proliferation was significantly lower in the natural aging group than in the young control group and that intervention with Heshouwuyin could reverse this phenomenon. Therefore, we further applied microarray analysis to screen out differentially expressed genes regulated by Heshouwuyin and related to cell apoptosis. The expression of these genes was observed by quantitative fluorescence PCR, immunofluorescence staining, and western blot. The results showed that the expression of 14-3-3σ was significantly lower and that the expression of DR6, BAX, caspase-3 and Cytc were significantly higher in the natural aging group than in the young control group, but intervention with Heshouwuyin significantly reversed this phenomenon. Moreover, the curative efficacy of Heshouwuyin after 60 days was better than that of Heshouwuyin after 30 days. Our study suggests that Heshouwuyin has anti-aging effects on the testis by means of inhibiting the occurrence of apoptosis in spermatogenic

Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data

OpenAIRE

Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris

2016-01-01

Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...

Single-nucleotide polymorphism in the 5-α-reductase gene (SRD5A2) is associated with increased prevalence of metabolic syndrome in chemotherapy-treated testicular cancer survivors.

Science.gov (United States)

Boer, Hink; Westerink, Nico-Derk L; Altena, Renske; Nuver, Janine; Dijck-Brouwer, D A Janneke; van Faassen, Martijn; Klont, Frank; Kema, Ido P; Lefrandt, Joop D; Zwart, Nynke; Boezen, H Marike; Smit, Andries J; Meijer, Coby; Gietema, Jourik A

2016-02-01

Chemotherapy-treated testicular cancer survivors are at risk for development of the metabolic syndrome, especially in case of decreased androgen levels. Polymorphisms in the gene encoding steroid 5-α-reductase type II (SRD5A2) are involved in altered androgen metabolism. We investigated whether single-nucleotide polymorphisms (SNPs) rs523349 (V89L) and rs9282858 (A49T) in SRD5A2 are associated with cardiometabolic status in testicular cancer survivors. In 173 chemotherapy-treated testicular cancer survivors, hormone levels and cardiometabolic status were evaluated cross-sectionally (median 5 years [range 3-20] after chemotherapy) and correlated with SNPs in SRD5A2. The metabolic syndrome was more prevalent in survivors who were homozygous or heterozygous variant for SRD5A2 rs523349 compared to wild type (33% versus 19%, P = 0.032). In particular, patients with lower testosterone levels (testicular cancer survivors homozygous or heterozygous variant for SNP rs523349 in SRD5A2. Altered androgen sensitivity appears to be involved in the development of adverse metabolic and vascular changes in testicular cancer survivors and is a target for intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hypothalamic-pituitary-testicular system following testicular X-irradiation

International Nuclear Information System (INIS)

Verjans, H.L.; Eik-Nes, K.B.

1976-01-01

Testes of adult, male rats were exposed to a total dose of 1500 R of X-irradiation. Testicular weight decreased from day 8 after X-ray treatment. This decrease was, however, precded by an increment of the testis weight on day 4 following treatment. X-ray treatment of testes was associated with significant increase in serum FSH. Testicular irradiation had, however, no effect on ventral prostate and seminal vesicles weights. Serum testosterone increased only on day 1, 2 and 4 after irradiation, while serum LH levels tended to increase from day 8 post-irradiation. These changes were not significant, however, when compared with non-irradiated controls. At 7, 13 and 20 days following 1500 R of bilateral, testicular X-irradiation, the hypothalamic-pituitary unit was still capable of responding to exogenous gonadotrophin releasing factor. Serum FSH may in male rats be regulated at least partly by circulating steroids of testicular origin and partly by an unknown factor of non-interstitial cell nature. (author)

Imaging gene expression in gene therapy

Energy Technology Data Exchange (ETDEWEB)

Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

1997-12-31

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

Testicular calculus: A rare case.

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Sen, Volkan; Bozkurt, Ozan; Demır, Omer; Tuna, Burcin; Yorukoglu, Kutsal; Esen, Adil

2015-01-01

Testicular calculus is an extremely rare case with unknown etiology and pathogenesis. To our knowledge, here we report the third case of testicular calculus. A 31-year-old man was admitted to our clinic with painful solid mass in left testis. After diagnostic work-up for a possible testicular tumour, he underwent inguinal orchiectomy and histopathologic examination showed a testicular calculus. Case hypothesis: Solid testicular lesions in young adults generally correspond to testicular cancer. Differential diagnosis should be done carefully. Future implications: In young adults with painful and solid testicular mass with hyperechogenic appearance on scrotal ultrasonography, testicular calculus must be kept in mind in differential diagnosis. Further reports on this topic may let us do more clear recommendations about the etiology and treatment of this rare disease.

Effect of chronic usage of tramadol on motor cerebral cortex and testicular tissues of adult male albino rats and the effect of its withdrawal: histological, immunohistochemical and biochemical study.

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Ghoneim, Fatma M; Khalaf, Hanaa A; Elsamanoudy, Ayman Z; Helaly, Ahmed N

2014-01-01

This study was designed to demonstrate the histopathological and biochemical changes in rat cerebral cortex and testicles due to chronic usage of tramadol and the effect of withdrawal. Thirty adult male rats weighing 180-200 gm were classified into three groups; group I (control group) group II (10 rats received 50 mg/kg/day of tramadol intraperitoneally for 4 weeks) and group III (10 rats received the same dose as group II then kept 4 weeks later to study the effect of withdrawal). Histological and immunohistochemical examination of cerebral cortex and testicular specimens for Bax (apoptotic marker) were carried out. Testicular specimens were examined by electron microscopy. RT-PCR after RNA extraction from both specimens was done for the genes of some antioxidant enzymes .Also, malondialdehyde (MDA) was measured colourimetrically in tissues homogenizate. The results of this study demonstrated histological changes in testicular and brain tissues in group II compared to group I with increased apoptotic index proved by increased Bax expression. Moreover in this group increased MDA level with decreased gene expression of the antioxidant enzymes revealed oxidative stress. Group III showed signs of improvement but not returned completely normal. It could be concluded that administration of tramadol have histological abnormalities on both cerebral cortex and testicular tissues associated with oxidative stress in these organs. Also, there is increased apoptosis in both organs which regresses with withdrawal. These findings may provide a possible explanation for delayed fertility and psychological changes associated with tramadol abuse.

Studies of testicular function after treatment for testicular tumor, 1

International Nuclear Information System (INIS)

Furuhata, Akihiko; Ogawa, Katsuaki; Hosaka, Masahiko; Sugawara, Toshimichi.

1985-01-01

Recently, the treatment for testicular tumor has improved. Preservation of testicular function in the treatment of testicular tumor is important, because the majority of the patients are young. We investigated the testicular function of patients with testicular tumor before, during and after treatment. As a part of this study, the fertility of patients with testicular tumor before and after treatment was evaluated. 1. Fourteen of 78 married patients (18 %) showed sterility for two or more years before treatment. 2. When semen was examined in 31 patients before treatment, only seven patients (23 %) showed normal sperm counts of more than 40 x 10 6 /ml, and 19 (61.3 %) showed oligospermia or azoospermia with sperm counts of less than 10 x 10 6 /ml. 3. Of 20 patients who underwent retroperitoneal lymphnode dissection, 15 developed ejaculation deficiency. Four other patients also developed ejaculation deficiency but recovered, and three of them rendered their wives pregnant. 4. Of 23 patients given radiotherapy, nine produced children both before and after treatment, nine produced children before treatment but showed sterility after treatment, and five showed sterility both before and after treatment. 5. Examination of semen was performed in 17 patients given radiotherapy and in five given chemotherapy. Many patients developed oligospermia or azoospermia after the treatments, but revealed a tendency to recover with time. Based on the results mentioned above, it is inferred that the ability to produce sperm in patients with testicular tumor after treatment decreases but the decrease tends to recover to normal with time. (author)

Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer

DEFF Research Database (Denmark)

Hoei-Hansen, Christina E; Holm, Mette; Rajpert-De Meyts, Ewa

2003-01-01

This study was prompted by a hypothesis that testicular germ cell cancer may be aetiologically linked to other male reproductive abnormalities as a part of the so-called 'testicular dysgenesis syndrome' (TDS). To corroborate the hypothesis of a common association of germ cell cancer with testicular...... dysgenesis, microscopic dysgenetic features were quantified in contralateral testicular biopsies in patients with a testicular germ cell tumour. Two hundred and eighty consecutive contralateral testicular biopsies from Danish patients with testicular cancer diagnosed in 1998-2001 were evaluated...... presenting with testicular germ cell neoplasms of the adolescent and young type. The findings therefore support the hypothesis that this cancer is part of a testicular dysgenesis syndrome. The presence of contralateral carcinoma in situ was higher in the present study than previously reported....

Testicular cancer risk in first- and second-generation immigrants to Denmark.

Science.gov (United States)

Myrup, Charlotte; Westergaard, Tine; Schnack, Tine; Oudin, Anna; Ritz, Christian; Wohlfahrt, Jan; Melbye, Mads

2008-01-02

Immigrant studies offer insights into the relative importance of environment and genes in disease etiology. There is considerable variation in testicular cancer incidence worldwide. We investigated testicular cancer risk in first- and second-generation immigrants to Denmark, a high-incidence country, to evaluate the relative influence of genes and environment and the potential timing of action of environmental factor(s). A cohort of 2.1 million men who were born since 1930 and lived in Denmark between 1968 and 2003 was established based on information in the Danish Civil Registration System, which included their immigration histories. Cancer histories were obtained from the Danish Cancer Registry. Testicular cancer risk was estimated as rate ratios (RRs) with 95% confidence intervals (CIs) based on log-linear Poisson regression. Overall, 4216 testicular cancer cases occurred during 43 million person-years of follow-up in 2.1 million men. These included 166 cases among 344,444 direct immigrants to Denmark and 13 cases among 56,189 men born in Denmark to immigrant parents. These first- and second-generation immigrants had RRs of testicular cancer of 0.37 (95% CI = 0.31 to 0.43) and 0.88 (95% CI = 0.51 to 1.53), respectively, compared with men born in Denmark of parents born in Denmark. The rate in first-generation immigrants was not modified by age at immigration or duration of stay and reflected that in the country of origin. The testicular cancer risk in first-generation immigrants was lower than that in native-born Danes and reflected that in the countries of origin, whereas the risk in second-generation immigrants was similar to that in natives of Denmark. Together these findings argue for a substantial influence of environmental factors limited to the period early in life, most probably to the period in utero.

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

Science.gov (United States)

Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

2016-06-01

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

Exposure to di(n-butyl)phthalate and benzo(a)pyrene alters IL-1β secretion and subset expression of testicular macrophages, resulting in decreased testosterone production in rats

International Nuclear Information System (INIS)

Zheng Shanjun; Tian Huaijun; Cao Jia; Gao Yuqi

2010-01-01

Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1β), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1β secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plus BaP (DBP + BaP: 50 + 1 or 250 + 5 mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250 mg/kg/day; BaP: 1 or 5 mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90 days, the relative expression of macrophage subsets and their functions changed. ED2 + testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1β secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1β secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1β, resulted in enhanced production of IL-1β as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis.

Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract

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Ceder Yvonne

2009-09-01

Full Text Available Abstract Background Beta-microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus. Methods Genes were identified in the Callithrix jacchus genome database using bioinformatics and transcripts were analyzed by RT-PCR and quantified by real time PCR in the presence of SYBR green. Results The common marmoset has five MSMB: one processed pseudogene and four functional genes. The latter encompass homologous genomic regions of 32-35 kb, containing the genes of 12-14 kb and conserved upstream and downstream regions of 14-19 kb and 3-4 kb. One gene, MSMB1, occupies the same position on the chromosome as the single human gene. On the same chromosome, but several Mb away, is another MSMB locus situated with MSMB2, MSMB3 and MSMB4 arranged in tandem. Measurements of transcripts demonstrated that all functional genes are expressed in the male genital tract, generating very high transcript levels in the prostate. The transcript levels in seminal vesicles and testis are two and four orders of magnitude lower. A single gene, MSMB3, accounts for more than 90% of MSMB transcripts in both the prostate and the seminal vesicles, whereas in the testis around half of the transcripts originate from MSMB2. These genes display rapid evolution with a skewed distribution of mutated nucleotides; in MSMB2 they affect nucleotides encoding the N-terminal Greek key domain, whereas in MSMB3 it is the C-terminal MSMB-unique domain that is affected. Conclusion Callitrichide monkeys have four functional MSMB that are all expressed in the male genital tract, but the product from one gene, MSMB3, will predominate in seminal

Potential Stemness of Frozen-Thawed Testicular Biopsies without Sperm in Infertile Men Included into the In Vitro Fertilization Programme

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Martin Stimpfel

2012-01-01

Full Text Available We describe the potential stemness of a small amount of frozen-thawed testicular tissue without sperm obtained by biopsy from six patients undergoing assisted reproductive treatment. The patients were diagnosed with Sertoli Cell-Only Syndrome alone or combined with maturation arrest. Trying to provide the natural stem cell niche for cultured stem cells, all isolated cells from enzymatically degraded biopsies where cultured together in different culture media and the presence of putative mesenchymal and putative pluripotent ES-like stem cells was indicated using different methods. High throughput real-time quantitative PCR followed by multivariate analysis revealed the formation of distinct cell clusters reflecting high degree of similarity and some of these cell clusters expressed the genes characteristic for pluripotent stem cells. In the presence of the follicular fluid, prepared as serum, putative testicular stem cells showed a certain degree of plasticity, and spontaneously differentiated into adipose-like and neuronal-like cells. Additionally, using differentiation protocols putative testicular stem cells were differentiated into neuronal- and pancreatic-like cells. This study shows that in assisted reproduction programmes, testicular tissue with no sperm might be an important source of stem cells, although it is discarded in daily medical practice; this requires further research.

Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations

DEFF Research Database (Denmark)

Skakkebaek, N E; Rajpert-De Meyts, Ewa; Jørgensen, N

2007-01-01

Recently a worldwide rise in the incidence of testicular germ cell cancer (TGCC) has been repeatedly reported. The changing disease pattern may signal that other testicular problems may also be increasing. We have reviewed recent research progress, in particular evidence gathered in the Nordic...... countries, which shows strong associations between testicular cancer, undescended testis, hypospadias, poor testicular development and function, and male infertility. These studies have led us to suggest the existence of a testicular dysgenesis syndrome (TDS), of which TGCC, undescended testis, hypospadias...... in TGCC rates of a population may be 'whistle blowers' of other reproductive health problems. As cancer registries are often of excellent quality - in contrast to registries for congenital abnormalities - health authorities should consider an increase in TGCC as a warning that other reproductive health...

A Meta-Analysis of the Relationship between Testicular Microlithiasis and Incidence of Testicular Cancer.

Science.gov (United States)

Wang, Tao; Liu, LuHao; Luo, JinTai; Liu, TaiSheng; Wei, AnYang

2015-04-29

There are many recent observational studies on testicular microlithiasis (TM) and risk of testicular cancer. Whether TM increases the risk of testicular cancer is still inconclusive. The objective of this updated meta-analysis was to synthesize evidence from clinical observational studies that evaluated the association between TM and testicular cancer. We identified eligible studies by searching the PubMed, Embase and Cochrane Library before March 2014. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-or fixed-model. A total of 14 studies involving 35,578 participants were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale systematic review, eleven studies were identified as relatively high-quality. TM was strong association with an increased incidence of testicular cancer (RR = 12.70, 95% CI: 8.18-19.71, P testicular cancer. More researches are warranted to clarify an understanding of the association between TM and risk of testicular cancer.

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

Science.gov (United States)

Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

Acute heat stress induces differential gene expressions in the testes of a broiler-type strain of Taiwan country chickens.

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Wang, Shih-Han; Cheng, Chuen-Yu; Tang, Pin-Chi; Chen, Chih-Feng; Chen, Hsin-Hsin; Lee, Yen-Pai; Huang, San-Yuan

2015-01-01

The expression of testicular genes following acute heat stress has been reported in layer-type roosters, but few similar studies have been conducted on broilers. This study investigated the effect of acute heat stress on the gene expression in the testes of a broiler-type strain of Taiwan country chickens. Roosters were subjected to acute heat stress (38°C) for 4 h, and then exposed to 25°C, with testes collected 0, 2, and 6 h after the cessation of heat stress, using non-heat-stressed roosters as controls (n = 3 roosters per group). The body temperature and respiratory rate increased significantly (pstress. The numbers of apoptotic cells increased 2 h after the acute heat stress (79 ± 7 vs. 322 ± 192, control vs. heat stress; pstressed chickens from those of the controls, including genes involved in the response to stimulus, protein metabolism, signal transduction, cell adhesion, transcription, and apoptosis. The mRNA expressions of upregulated genes, including HSP25, HSP90AA1, HSPA2, and LPAR2, and of downregulated genes, including CDH5, CTNNA3, EHF, CIRBP, SLA, and NTF3, were confirmed through quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, numerous transcripts in the testes exhibited distinct expressions between the heat-stressed broiler-type and layer-type chickens. We concluded that the transcriptional responses of testes to acute heat stress may differ between the broiler-type and layer-type roosters. Whether the differential expression patterns associate with the heat-tolerance in the strains require a further exploration.

Testicular microlithiasis in patients with testicular cancer in the United Kingdom and in Denmark

DEFF Research Database (Denmark)

Pedersen, Malene Roland; Horsfield, Catherine; Foot, Oliver

2018-01-01

INTRODUCTION: Testicular cancer is the most common type of cancer in young Caucasian men. It has been suggested that testicular microlithiasis (TML) is a premalignant condition. This study's objective was to investigate TML histology prevalence in testicular cancer patients in two European...... populations. METHODS: We analysed archived histopathology orchiectomy specimens from 152 patients diagnosed with testicular cancer at Fredericia Hospital in Denmark from 2004 to 2014, and 106 patients diagnosed at St Thomas' Hospital in London from 2011 to 2015. RESULTS: The Danish patients' median age was 37...... in seminomas than in non-seminomas.
 CONCLUSIONS: The English testicular cancer patients had a statistically significantly higher TML prevalence than the Danish patients. This observation questions the hypothesised biological association between TML and testicular 
cancer. FUNDING: The Region of Southern...

Testicular Cancer—Patient Version

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Testicular cancer most often begins in germ cells (cells that make sperm). It is rare and is most frequently diagnosed in men 20-34 years old. Most testicular cancers can be cured, even if diagnosed at an advanced stage. Start here to find information on testicular cancer treatment, screening, and statistics.

Testicular cancer update.

Science.gov (United States)

Adra, Nabil; Einhorn, Lawrence H

2017-05-01

The advances seen in the treatment of testicular cancer are among the great achievements in modern medicine. These advances were made possible by the collaborative efforts of cancer researchers around the world. Investigators have been able to address many questions regarding the treatment of patients with disease limited to the testis, those with metastasis to the retroperitoneum only, and those with advanced metastatic disease. Questions answered include the chemotherapeutic agents to be used and in what combinations, the proper intensity of treatment and appropriate dosing, the optimal number of cycles of chemotherapy according to validated risk stratification, appropriate surgical approaches that preserve sexual function, the treatment of relapsed disease, what supportive care measures to take, and survivorship issues following treatment of testicular cancer. Today, cure is achievable in 95% of all patients with testicular cancer and 80% of those who have metastatic disease. Despite remarkable results with frontline and salvage combination chemotherapy, metastatic testicular cancer remains incurable in approximately 10% of patients, and novel treatment approaches are warranted. This review highlights past and recent discoveries in the treatment of patients with testicular cancer.

In vivo effects of chronic contamination with 137 cesium on testicular and adrenal steroidogenesis

International Nuclear Information System (INIS)

Grignard, Elise; Gueguen, Yann; Grison, Stephane; Gourmelon, Patrick; Souidi, Maamar; Lobaccaro, Jean-Marc A.

2008-01-01

More than 20 years after Chernobyl nuclear power plant explosion, radionuclids are still mainly bound to the organic soil layers. The radiation exposure is dominated by the external exposure to gamma-radiation following the decay of 137 Cs and by soil-to-plant-to-human transfer of 137 Cs into the food chain. Because of this persistence of contamination with 137 Cs, questions regarding public health for people living in contaminated areas were raised. We investigated the biological effects of chronic exposure to 137 Cs on testicular and adrenal steroidogenesis metabolisms in rat. Animals were exposed to radionuclide in their drinking water for 9 months at a dose of 6,500 Bq/l (610 Bq/kg/day). Cesium contamination decreases the level of circulating 17β-estradiol, and increases corticosterone level. In testis, several nuclear receptors messenger expression is disrupted; levels of mRNA encoding Liver X receptor α (LXRα) and LXRβ are increased, whereas farnesoid X receptor mRNA presents a lower level. Adrenal metabolism presents a paradoxical decrease in cyp11a1 gene expression. In conclusion, our results show for the first time molecular and hormonal modifications in testicular and adrenal steroidogenic metabolism, induced by chronic contamination with low doses of 137 Cs. (orig.)

In vivo effects of chronic contamination with 137 cesium on testicular and adrenal steroidogenesis

Energy Technology Data Exchange (ETDEWEB)

Grignard, Elise; Gueguen, Yann; Grison, Stephane; Gourmelon, Patrick; Souidi, Maamar [Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Toxicology, BP no 17, Fontenay-aux-Roses Cedex (France); Lobaccaro, Jean-Marc A. [UMR Universite Blaise Pascal-CNRS 6547, Physiologie Comparee et Endocrinologie Moleculaire, Centre de Recherche en Nutrition Humaine d' Auvergne, Aubiere Cedex (France)

2008-09-15

More than 20 years after Chernobyl nuclear power plant explosion, radionuclids are still mainly bound to the organic soil layers. The radiation exposure is dominated by the external exposure to gamma-radiation following the decay of {sup 137}Cs and by soil-to-plant-to-human transfer of {sup 137}Cs into the food chain. Because of this persistence of contamination with {sup 137}Cs, questions regarding public health for people living in contaminated areas were raised. We investigated the biological effects of chronic exposure to {sup 137}Cs on testicular and adrenal steroidogenesis metabolisms in rat. Animals were exposed to radionuclide in their drinking water for 9 months at a dose of 6,500 Bq/l (610 Bq/kg/day). Cesium contamination decreases the level of circulating 17{beta}-estradiol, and increases corticosterone level. In testis, several nuclear receptors messenger expression is disrupted; levels of mRNA encoding Liver X receptor {alpha} (LXR{alpha}) and LXR{beta} are increased, whereas farnesoid X receptor mRNA presents a lower level. Adrenal metabolism presents a paradoxical decrease in cyp11a1 gene expression. In conclusion, our results show for the first time molecular and hormonal modifications in testicular and adrenal steroidogenic metabolism, induced by chronic contamination with low doses of {sup 137}Cs. (orig.)

Antioxidants enhance the recovery of three cycles of bleomycin, etoposide, and cisplatin-induced testicular dysfunction, pituitary-testicular axis, and fertility in rats.

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Kilarkaje, Narayana; Mousa, Alyaa M; Al-Bader, Maie M; Khan, Khalid M

2013-10-01

To investigate the effects of an antioxidant cocktail (AC) on bleomycin, etoposide, and cisplatin (BEP)-induced testicular dysfunction. In vivo study. Research laboratory. Adult male and female Sprague-Dawley rats. The rats were treated with three cycles of 21 days each of therapeutically relevant dose levels of BEP (0.75, 7.5, and 1.5 mg/kg) with or without the AC (a mixture of α-tocopherol, L-ascorbic acid, Zn, and Se). Sperm parameters, fertility, serum hormone levels (ELISA), testicular histopathology, and expression of proliferating cell nuclear antigen (PCNA), and transferrin (Western blotting and immunohistochemistry) were evaluated at the end of treatment and a 63-day recovery period. At the end of treatment, the AC improved BEP-induced decrease in sperm motility and increase in abnormality but had no effect on reduced sperm count, fertility, and tubular atrophy, although it up-regulated germ cell proliferation. The AC normalized reduced inhibin B levels, but had no effect on decreased transferrin and testosterone and elevated LH levels. At the end of the recovery period, the AC enhanced the expression of PCNA and transferrin, repopulation of germ cells, LH-testosterone axis, and fertility, but had no effect on reduced FSH and elevated inhibin B levels. The antioxidants protect and then enhance the recovery of testicular and reproductive endocrine functions when administered concomitantly with BEP therapy. The AC may be beneficial to regain testicular functions after chemotherapy. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Testicular self-examination and testicular cancer: a cost-utility analysis.

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Aberger, Michael; Wilson, Bradley; Holzbeierlein, Jeffrey M; Griebling, Tomas L; Nangia, Ajay K

2014-12-01

The United States Preventive Services Task Force (USPSTF) has recommended against testicular self-examinations (TSE) or clinical examination for testicular cancer screening. However, in this recommendation there was no consideration of the significant fiscal cost of treating advanced disease versus evaluation of benign disease. In this study, a cost-utility validation for TSE was performed. The cost of treatment for an advanced-stage testicular tumor (both seminomatous and nonseminomatous) was compared to the cost of six other scenarios involving the clinical assessment of a testicular mass felt during self-examination (four benign and two early-stage malignant). Medicare reimbursements were used as an estimate for a national cost standard. The total treatment cost for an advanced-stage seminoma ($48,877) or nonseminoma ($51,592) equaled the cost of 313-330 benign office visits ($156); 180-190 office visits with scrotal ultrasound ($272); 79-83 office visits with serial scrotal ultrasounds and labs ($621); 6-7 office visits resulting in radical inguinal orchiectomy for benign pathology ($7,686) or 2-3 office visits resulting in treatment and surveillance of an early-stage testicular cancer ($17,283: seminoma, $26,190: nonseminoma). A large number of clinical evaluations based on the TSE for benign disease can be made compared to the cost of one missed advanced-stage tumor. An average of 2.4 to 1 cost benefit ratio was demonstrated for early detected testicular cancer versus advanced-stage disease. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication.

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Lee, Gyung Min; Ko, Jung Min; Shin, Choong Ho; Yang, Sei Won

2014-06-01

The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

Testicular germinal tumors

International Nuclear Information System (INIS)

Fresco, R.

2010-01-01

This work is about diagnosis, treatment and monitoring of testicular germinal tumors. The presumed diagnosis is based in the anamnesis, clinical examination, testicular ultrasound and tumor markers. The definitive diagnosis is obtained through the inguinal radical orchidectomy

Public awareness of testicular cancer and testicular self-examination in academic environments: a lost opportunity

Directory of Open Access Journals (Sweden)

Henry A. A. Ugboma

2011-01-01

Full Text Available BACKGROUND: Although testicular cancer is the most common cancer among 18- to 50-year-old males, healthcare providers seldom teach testicular self-examination techniques to clients, thus potentially missing opportunities for early detection. This form of cancer is easily diagnosable by testicular self-examination and is 96% curable if detected early. Periodic self-examination must be performed for early detection. Knowledge deficits and sociocultural norms contribute to low levels of health-related knowledge in most patients, resulting in undue delays before seeking medical advice. OBJECTIVE: Our aim is to assess the level of awareness of testicular cancer and the prevalence of the practice of testicular self-examination in academic environments to enable appropriate interventions. METHOD: A cross-sectional survey was administered to 750 consecutive males aged 18-50 years in three tertiary institutions in Port Harcourt from October 2008 to April 2009. RESULT: Knowledge or awareness of testicular cancer was poor. Almost all of the respondents were unaware that testicular lumps may be signs of cancer. A lump was typically construed as a benign carbuncle or something that could resolve spontaneously. The main factor contributing to respondents' lack of knowledge of testicular cancer was that few reported that they were "ever taught about testicular self-examination." CONCLUSION: Young adult men are unaware of their risk for testicular cancer, which is the most common neoplasm in this age group. Healthcare providers are not informing them of this risk, nor are they teaching them the simple early detection technique of self-examination of the testes.

[Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and individuals with infertility associated with AZFc deletion of the Y chromosome].

Science.gov (United States)

Nemtsova, M V; Ivkin, E V; Simonova, O A; Rudenko, V V; Chernykh, V B; Mikhaylenko, D S; Loran, O B

2016-01-01

Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to

Binding of Nickel to Testicular Glutamate–Ammonia Ligase Inhibits Its Enzymatic Activity

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SUN, YINGBIAO; OU, YOUNG; CHENG, MIN; RUAN, YIBING; VAN DER HOORN, FRANS A.

2016-01-01

SUMMARY Exposure to nickel has been shown to cause damage to the testis in several animal models. It is not known if the testis expresses protein(s) that can bind nickel. To test this, we used a nickel-binding assay to isolate testicular nickel-binding proteins. We identified glutamate–ammonia ligase (GLUL) as a prominent nickel-binding protein by mass spectrometry. Protein analysis and reverse transcriptase polymerase chain reaction showed that GLUL is expressed in the testis, predominantly in interstitial cells. We determined that GLUL has a higher affinity for nickel than for its regular co-factor manganese. We produced an enzymatically active, recombinant GLUL protein. Upon binding, nickel interferes with the manganese-catalyzed enzymatic activity of recombinant GLUL protein. We also determined that GLUL activity in testes of animals exposed to nickel sulfate is reduced. Our results identify testicular GLUL as the first testicular protein shown to be affected by nickel exposure. PMID:21254280

Simvastatin and Dipentyl Phthalate Lower Ex vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat

Science.gov (United States)

Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/transport, and...

FARO server: Meta-analysis of gene expression by matching gene expression signatures to a compendium of public gene expression data

DEFF Research Database (Denmark)

Manijak, Mieszko P.; Nielsen, Henrik Bjørn

2011-01-01

circumvented by instead matching gene expression signatures to signatures of other experiments. FINDINGS: To facilitate this we present the Functional Association Response by Overlap (FARO) server, that match input signatures to a compendium of 242 gene expression signatures, extracted from more than 1700...... Arabidopsis microarray experiments. CONCLUSIONS: Hereby we present a publicly available tool for robust characterization of Arabidopsis gene expression experiments which can point to similar experimental factors in other experiments. The server is available at http://www.cbs.dtu.dk/services/faro/....

Digital gene expression analysis of gene expression differences within Brassica diploids and allopolyploids.

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Jiang, Jinjin; Wang, Yue; Zhu, Bao; Fang, Tingting; Fang, Yujie; Wang, Youping

2015-01-27

Brassica includes many successfully cultivated crop species of polyploid origin, either by ancestral genome triplication or by hybridization between two diploid progenitors, displaying complex repetitive sequences and transposons. The U's triangle, which consists of three diploids and three amphidiploids, is optimal for the analysis of complicated genomes after polyploidization. Next-generation sequencing enables the transcriptome profiling of polyploids on a global scale. We examined the gene expression patterns of three diploids (Brassica rapa, B. nigra, and B. oleracea) and three amphidiploids (B. napus, B. juncea, and B. carinata) via digital gene expression analysis. In total, the libraries generated between 5.7 and 6.1 million raw reads, and the clean tags of each library were mapped to 18547-21995 genes of B. rapa genome. The unambiguous tag-mapped genes in the libraries were compared. Moreover, the majority of differentially expressed genes (DEGs) were explored among diploids as well as between diploids and amphidiploids. Gene ontological analysis was performed to functionally categorize these DEGs into different classes. The Kyoto Encyclopedia of Genes and Genomes analysis was performed to assign these DEGs into approximately 120 pathways, among which the metabolic pathway, biosynthesis of secondary metabolites, and peroxisomal pathway were enriched. The non-additive genes in Brassica amphidiploids were analyzed, and the results indicated that orthologous genes in polyploids are frequently expressed in a non-additive pattern. Methyltransferase genes showed differential expression pattern in Brassica species. Our results provided an understanding of the transcriptome complexity of natural Brassica species. The gene expression changes in diploids and allopolyploids may help elucidate the morphological and physiological differences among Brassica species.

Testicular growth and development in puberty.

Science.gov (United States)

Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

2017-06-01

To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

Epigenetic: a molecular link between testicular cancer and environmental exposures.

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Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A; Volle, David H

2012-01-01

In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

Varicocele and testicular function

Directory of Open Access Journals (Sweden)

Alexander W Pastuszak

2015-01-01

Full Text Available Testicular varicocele, a dilation of the veins of the pampiniform plexus thought to increase testicular temperature via venous congestion, is commonly associated with male infertility. Significant study has clarified the negative impact of varicocele on semen parameters and more recent work has shed light on its detrimental effects on the molecular and ultrastructural features of sperm and the testicular microenvironment, as well as more clearly defined the positive impacts of treatment on couples′ fertility. The relationship between varicocele and testicular endocrine function, while known for some time based on histologic evaluation, has become more apparent in the clinical setting with a growing link between varicocele and hypogonadism. Finally, in the pediatric setting, while future study will clarify the impact of varicocele on fertility and testicular function, recent work supports a parallel effect of varicocele in adolescents and adults, suggesting a re-evaluation of current treatment approaches in light of the progressive nature of the condition and potential increased risk of future disease.

Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

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Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

2014-05-01

Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

Directory of Open Access Journals (Sweden)

Benjamin Mayne

2016-10-01

Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

Epidemiology of testicular cancer: an overview.

Science.gov (United States)

Garner, Michael J; Turner, Michelle C; Ghadirian, Parviz; Krewski, Daniel

2005-09-01

Testicular cancer is a rare disease, accounting for 1.1% of all malignant neoplasms in Canadian males. Despite the low overall incidence of testicular cancer, it is the most common malignancy among young men. The incidence rate of testicular cancer has been increasing since the middle of the 20th century in many western countries. However, the etiology of testicular cancer is not well understood. A search of the peer-reviewed literature was conducted to identify important articles for review and inclusion in this overview of the epidemiology of testicular cancer. Most of the established risk factors are related to early life events, including cryptorchidism, carcinoma in situ and in utero exposure to estrogens. Occupational, lifestyle, socioeconomic and other risk factors have demonstrated mixed associations with testicular cancer. Although there are few established risk factors for testicular cancer, some appear to be related to hormonal balance at various life stages. Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, although they are not likely involved in cancer initiation. In addition to summarizing the current epidemiologic evidence on risk factors for testicular cancer, we suggest future research directions that may elucidate the etiology of testicular cancer.

Androgen action via testicular arteriole smooth muscle cells is important for Leydig cell function, vasomotion and testicular fluid dynamics.

Directory of Open Access Journals (Sweden)

Michelle Welsh

2010-10-01

Full Text Available Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO. Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis.

Testicular biopsy in psittacine birds (Psittaciformes): impact of endoscopy and biopsy on health, testicular morphology, and sperm parameters.

Science.gov (United States)

Hänse, Maria; Krautwald-Junghanns, Maria-Elisabeth; Reitemeier, Susanne; Einspanier, Almuth; Schmidt, Volker

2013-12-01

Histologic examination of a testicular biopsy sample may be required to evaluate the reproductive status of male psittacine birds. The purpose of this study was to evaluate the viability of testicular sampling from live birds by assessing the impact on the birds' health, testicular integrity, and sperm quality. Testicular biopsy samples were obtained by endoscopy 4 times during 12 months from 9 cockatiels (Nymphicus hollandicus) and 7 rose-ringed parakeets (Psittacula krameri). Only 2 of 16 birds showed testicular cicatrization or divided testicular tissue after a single endoscopy. Further complications, such as damage to the air sacs or bleeding, predominantly occurred in subsequent endoscopies. In both species, endoscopy and testicular biopsy caused only minor or transient effects on sperm production and sperm quality. These results support that a single testicular biopsy is a viable method for evaluating the reproductive status of male psittacine birds.

Differential Gene Expression and Aging

Directory of Open Access Journals (Sweden)

Laurent Seroude

2002-01-01

Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

Testicular regulation of neuronal glucose and monocarboxylate transporter gene expression profiles in CNS metabolic sensing sites during acute and recurrent insulin-induced hypoglycemia.

Science.gov (United States)

Vavaiya, Kamlesh V; Paranjape, Sachin A; Briski, Karen P

2007-01-01

Recurrent insulin-induced hypoglycemia (RIIH) impairs glucose counter-regulatory function in male humans and rodents and, in the latter, diminishes neuronal activation in CNS structures that monitor metabolic homeostasis, including the lateral hypothalamic area (LHA) and dorsal vagal complex (DVC). We investigated whether habituated neuronal reactivity in CNS sensing sites to hypoglycemia is correlated with modified monocarboxylate and/or glucose uptake by using quantitative real-time RT-PCR to analyze neuronal monocarboxylate transporter (MCT2) and glucose transporter variant (GLUT and GLUT4) gene expression profiles in the microdissected LHA, ventromedial nucleus hypothalamus (VMH), and DVC after one or multiple insulin injections. Because orchidectomy (ORDX) maintains uniform glycemic responses to RIIH in male rats, we also examined whether regional gene response patterns are testes dependent. In the intact male rat DVC, MCT2, GLUT3, and GLUT4 gene expression was not altered by acute hypoglycemia but was enhanced by RIIH. MCT2 and GLUT3 mRNA levels in the ORDX rat DVC did not differ among groups, but GLUT4 transcripts were progressively increased by acute and recurrent hypoglycemia. Precedent hypoglycemia decreased or increased basal MCT2 and GLUT4 gene expression, respectively, in the intact rat LHA; LHA GLUT3 transcription was augmented by RIIH in intact rats only. Acute hypoglycemia suppressed MCT2, GLUT3, and GLUT4 gene expression in the intact rat VMH, a response that was abolished by RIIH. In ORDX rats, VMH gene transcript levels were unchanged in response to one dose of insulin but were selectively diminished during RIIH. These data demonstrate site-specific, testes-dependent effects of acute and recurrent hypoglycemia on neuronal metabolic substrate transporter gene expression in characterized rat brain metabolic sensing loci and emphasize the need to assess the impact of potential alterations in glucose and lactate uptake during RIIH on general and

Polycistronic gene expression in Aspergillus niger.

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Schuetze, Tabea; Meyer, Vera

2017-09-25

Genome mining approaches predict dozens of biosynthetic gene clusters in each of the filamentous fungal genomes sequenced so far. However, the majority of these gene clusters still remain cryptic because they are not expressed in their natural host. Simultaneous expression of all genes belonging to a biosynthetic pathway in a heterologous host is one approach to activate biosynthetic gene clusters and to screen the metabolites produced for bioactivities. Polycistronic expression of all pathway genes under control of a single and tunable promoter would be the method of choice, as this does not only simplify cloning procedures, but also offers control on timing and strength of expression. However, polycistronic gene expression is a feature not commonly found in eukaryotic host systems, such as Aspergillus niger. In this study, we tested the suitability of the viral P2A peptide for co-expression of three genes in A. niger. Two genes descend from Fusarium oxysporum and are essential to produce the secondary metabolite enniatin (esyn1, ekivR). The third gene (luc) encodes the reporter luciferase which was included to study position effects. Expression of the polycistronic gene cassette was put under control of the Tet-On system to ensure tunable gene expression in A. niger. In total, three polycistronic expression cassettes which differed in the position of luc were constructed and targeted to the pyrG locus in A. niger. This allowed direct comparison of the luciferase activity based on the position of the luciferase gene. Doxycycline-mediated induction of the Tet-On expression cassettes resulted in the production of one long polycistronic mRNA as proven by Northern analyses, and ensured comparable production of enniatin in all three strains. Notably, gene position within the polycistronic expression cassette matters, as, luciferase activity was lowest at position one and had a comparable activity at positions two and three. The P2A peptide can be used to express at

Primary Testicular B-cell Lymphoma

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Aykut Buğra Şentürk

2015-12-01

Full Text Available Primary testicular lymphoma constitutes only 1-7% of all testicular neoplasms and less than 1% of all non-Hodgkin lymphoma. We report a 69-year-old man who presented with a painful right testicular mass. Treatment modalities consist of surgical excision, chemotherapy and radiation therapy, however there are no standardized treatment options.

Intermittent Testicular Torsion

African Journals Online (AJOL)

2017-06-02

Jun 2, 2017 ... had prior episodes of testicular pain, suggesting that they may have had intermittent torsion before .... None of the patients had antecedent history of sexual exposure, fever, or urinary tract infection .... torsion of the spermatic cord portends an increased risk of acute testicular infarction. J Urol 2008;180 4 ...

Subfertility and Risk of Testicular Cancer in the EPSAM Case-Control Study.

Science.gov (United States)

Grasso, Chiara; Zugna, Daniela; Fiano, Valentina; Robles Rodriguez, Nena; Maule, Milena; Gillio-Tos, Anna; Ciuffreda, Libero; Lista, Patrizia; Segnan, Nereo; Merletti, Franco; Richiardi, Lorenzo

2016-01-01

It has been suggested that subfertility and testicular cancer share genetic and environmental risk factors. We studied both subfertility and the strongest known testicular cancer susceptibility gene, the c-KIT ligand (KITLG), whose pathway is involved in spermatogenesis. The EPSAM case-control study is comprised of testicular cancer patients from the Province of Turin, Italy, diagnosed between 1997 and 2008. The present analysis included 245 cases and 436 controls from EPSAM, who were aged 20 years or older at diagnosis/recruitment. The EPSAM questionnaire collected information on factors such as number of children, age at first attempt to conceive, duration of attempt to conceive, use of assisted reproduction techniques, physician-assigned diagnosis of infertility, number of siblings, and self-reported cryptorchidism. Genotyping of the KITLG single nucleotide polymorphism (SNP) rs995030 was performed on the saliva samples of 202 cases and 329 controls. Testicular cancer was associated with the number of children fathered 5 years before diagnosis (odds ratio (OR) per additional child: 0.78, 95% confidence interval (CI): 0.58-1.04) and sibship size (OR per additional sibling: 0.76, 95% CI: 0.66-0.88). When considering the reproductive history until 1 year before diagnosis, attempting to conceive for at least 12 months or fathering a child using assisted reproduction techniques was not associated with the risk of testicular cancer, nor was age at first attempt to conceive or physician-assigned diagnosis of infertility. The SNP rs995030 was strongly associated with risk of testicular cancer (per allele OR: 1.83; 95%CI: 1.26-2.64), but it did not modify the association between number of children and the risk of testicular cancer. This study supports the repeatedly reported inverse association between number of children and risk of testicular cancer, but it does not find evidence of an association for other indicators of subfertility.

Comparison of global gene expression profiles of microdissected human foetal Leydig cells with their normal and hyperplastic adult equivalents

DEFF Research Database (Denmark)

Lottrup, Grete; Belling, Kirstine González-Izarzugaza; Leffers, Henrik

2017-01-01

the normally clustered and hyperplastic ALCs.WHAT IS KNOWN ALREADY: LCs are the primary androgen producing cells in males throughout development and appear in chronologically distinct populations; FLCs, neonatal LCs and ALCs. ALCs are responsible for progression through puberty and for maintenance...... of reproductive functions in adulthood. In patients with reproductive problems, such as infertility or testicular cancer, and especially in men with high gonadotrophin levels, LC function is often impaired, and LCs may cluster abnormally into hyperplastic micronodules (defined as clusters of > 15 LCs in a cross...... with reproductive disorders possibly reflect subtle changes in the expression of many genes rather than regulatory changes of single genes or pathways. The study provides new insights into the development and maturation of human LCs by the identification of a number of potential functional markers for FLC and ALC....

Chromosome 15 structural abnormalities: effect on IGF1R gene expression and function

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Rossella Cannarella

2017-09-01

Full Text Available Insulin-like growth factor 1 receptor (IGF1R, mapping on the 15q26.3 chromosome, is required for normal embryonic and postnatal growth. The aim of the present study was to evaluate the IGF1R gene expression and function in three unrelated patients with chromosome 15 structural abnormalities. We report two male patients with the smallest 15q26.3 chromosome duplication described so far, and a female patient with ring chromosome 15 syndrome. Patient one, with a 568 kb pure duplication, had overgrowth, developmental delay, mental and psychomotor retardation, obesity, cryptorchidism, borderline low testis volume, severe oligoasthenoteratozoospermia and gynecomastia. We found a 1.8-fold increase in the IGF1R mRNA and a 1.3-fold increase in the IGF1R protein expression (P < 0.05. Patient two, with a 650 kb impure duplication, showed overgrowth, developmental delay, mild mental retardation, precocious puberty, low testicular volume and severe oligoasthenoteratozoospermia. The IGF1R mRNA and protein expression was similar to that of the control. Patient three, with a 46,XX r(15 (p10q26.2 karyotype, displayed intrauterine growth retardation, developmental delay, mental and psychomotor retardation. We found a <0.5-fold decrease in the IGF1R mRNA expression and an undetectable IGF1R activity. After reviewing the previously 96 published cases of chromosome 15q duplication, we found that neurological disorders, congenital cardiac defects, typical facial traits and gonadal abnormalities are the prominent features in patients with chromosome 15q duplication. Interestingly, patients with 15q deletion syndrome display similar features. We speculate that both the increased and decreased IGF1R gene expression may play a role in the etiology of neurological and gonadal disorders.

Testicular Cancer and Testicular Self-Examination; Knowledge, Attitudes and Practice in Final Year Medical Students in Nigeria

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Ugwumba, Fred O; Ekwueme, Osa Eloka C; Okoh, Agharighom D

2016-11-01

The testicular cancer (TCa) incidence is increasing in many countries, with age-standardized incidence rates up to 7.8/100,000 men in the Western world, although reductions in mortality and increasingly high cure rates are being witnessed at the same time. In Africa, where rates are lower, presentation is often late and morbidity and mortality high. Given this scenario, awareness of testicular cancer and practice of testicular self-examination among future first response doctors is very important. This study was conducted to determine knowledge and attitude to testicular cancer, and practice of testicular self-examination (TSE) among final (6th) year medical students. In addition, the effect of an intervention in the form of a single PowerPoint® lecture, lasting 40 minutes with image content on testicular cancer and testicular self examination was assessed. Pre and post intervention administration of a self-administered structured pre tested questionnaire was performed on 151 medical students, 101 of whom returned answers (response rate of 66.8%). In the TC domain, there was a high level of awareness of testicular cancer, but poor knowledge of the age group most affected, with significant improvement post intervention (ptesticular self-examination pre-intervention was found considering the nature of the study group..Respondents had surprisingly weak/poor responses to the question “How important to men’s health is regular testicular self-examination?” Answers to the questions “Do you think it is worthwhile to examine your testis regularly?” and “Would you be interested in more information on testicular cancer and testicular self-examination?” were also suboptimal, but improved post intervention ptesticular cancer in the curricula of medical schools and other training institutions for health care personnel. Creative Commons Attribution License

Low hypoxia inducible factor-1α (HIF-1α) expression in testicular germ cell tumors - a major reason for enhanced chemosensitivity?

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Shenoy, Niraj; Dronca, Roxana; Quevedo, Fernando; Boorjian, Stephen A; Cheville, John; Costello, Brian; Kohli, Manish; Witzig, Thomas; Pagliaro, Lance

2017-08-01

The molecular basis for enhanced chemosensitivity of testicular germ cell tumors (GCT) has been an area of great interest, as it could potentially give us therapeutic leads in other resistant malignancies. Thus far, however, the increased sensitivity of GCT has been variously attributed to multiple factors - an inability to detoxify cisplatin, a lack of export pumps, an inability to repair the DNA damage, an intact apoptotic cascade and lack of p53 mutation; but a unifying underlying etiology leading to the aforementioned processes and having a translational implication has so far been elusive. Herein, we offer evidence to support a potential significant role for the previously demonstrated low hypoxia inducible factor-1α (HIF-1α) expression in mediating the general exquisite chemosensitivity of testicular GCT, through the aforementioned processes. This molecular mechanism based hypothesis could have a significant translational implication in platinum refractory GCT as well as other platinum resistant malignancies.

Effects of long-term heat stress and dietary restriction on the expression of genes of steroidogenic pathway and small heat-shock proteins in rat testicular tissue.

Science.gov (United States)

Bozkaya, F; Atli, M O; Guzeloglu, A; Kayis, S A; Yildirim, M E; Kurar, E; Yilmaz, R; Aydilek, N

2017-08-01

The aim was to investigate the effects of long-term heat stress and dietary restriction on the expression of certain genes involving in steroidogenic pathway and small heat-shock proteins (sHSPs) in rat testis. Sprague Dawley rats (n = 24) were equally divided into four groups. Group I and II were kept at an ambient temperature of 22°C, while Groups III and IV were reared at 38°C for 9 weeks. Feed was freely available for Group I and Group III, while Group II and Group IV were fed 60% of the diet consumed by their ad libitum counterparts. At the end of 9 weeks, testicles were collected under euthanasia. Total RNA was isolated from testis tissue samples. Expression profiles of the genes encoding androgen-binding protein, follicle-stimulating hormone receptor, androgen receptor, luteinising hormone receptor, steroidogenic acute regulatory protein (StAR), cyclooxygenase-2 and sHSP genes were assessed at mRNA levels using qPCR. Long-term heat stress decreased the expression of StAR and HspB10 genes while dietary restriction upregulated StAR gene expression. The results suggested that long-term heat stress negatively affected the expression of StAR and HspB10 genes and the dietary restriction was able to reverse negative effect of heat stress on the expression of StAR gene in rat testis. © 2016 Blackwell Verlag GmbH.

Gene expression inference with deep learning.

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Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

2016-06-15

Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Testicular Torsion (For Parents)

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... Parents Kids Teens Hernias Ultrasound: Scrotum Undescended Testicles Male Reproductive System PQ: I have a lump on one of ... to Do a Testicular Self-Exam (Slideshow) Varicocele Male Reproductive System Testicular Torsion View more About Us Contact Us ...

Male-biased genes in catfish as revealed by RNA-Seq analysis of the testis transcriptome.

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Fanyue Sun

Full Text Available BACKGROUND: Catfish has a male-heterogametic (XY sex determination system, but genes involved in gonadogenesis, spermatogenesis, testicular determination, and sex determination are poorly understood. As a first step of understanding the transcriptome of the testis, here, we conducted RNA-Seq analysis using high throughput Illumina sequencing. METHODOLOGY/PRINCIPAL FINDINGS: A total of 269.6 million high quality reads were assembled into 193,462 contigs with a N50 length of 806 bp. Of these contigs, 67,923 contigs had hits to a set of 25,307 unigenes, including 167 unique genes that had not been previously identified in catfish. A meta-analysis of expressed genes in the testis and in the gynogen (double haploid female allowed the identification of 5,450 genes that are preferentially expressed in the testis, providing a pool of putative male-biased genes. Gene ontology and annotation analysis suggested that many of these male-biased genes were involved in gonadogenesis, spermatogenesis, testicular determination, gametogenesis, gonad differentiation, and possibly sex determination. CONCLUSION/SIGNIFICANCE: We provide the first transcriptome-level analysis of the catfish testis. Our analysis would lay the basis for sequential follow-up studies of genes involved in sex determination and differentiation in catfish.

Cryopreservation of testicular tissue before long-term testicular cell culture does not alter in vitro cell dynamics

NARCIS (Netherlands)

Baert, Yoni; Braye, Aude; Struijk, Robin B.; van Pelt, Ans M. M.; Goossens, Ellen

2015-01-01

To assess whether testicular cell dynamics are altered during long-term culture after testicular tissue cryopreservation. Experimental basic science study. Reproductive biology laboratory. Testicular tissue with normal spermatogenesis was obtained from six donors. None. Detection and comparison of

Association of testicular echogenicity, scrotal circumference, testicular volume and testosterone concentration in buffaloes

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Henry D.M. Ayala

2016-12-01

Full Text Available ABSTRACT. Ayala H.D.M., Ribeiro H.F.L., Rolim Filho S.T., Silva E.V.C. & Vale W.G. Association of testicular echogenicity, scrotal circumference, testicular volume and testosterone concentration in buffaloes. [Associação entre a ecogenicidade, circunferência escrotal, volume testicular e concentração de testosterona em búfalos.] Revista Brasileira de Medicina Veterinária, 38(4:334-340, 2016. Programa de Pós-Graduação em Ciencia Animal, Universidade Federal do Pará, Rua Augusto Corrêa 1, Campus Universitário do Guamá, Belém, PA 66075-110, Brazil. E-mail wm.vale@hotmail.com This article aimed to discuss the changes in the testicular parenchyma, analyzed by the use of ultrasonography, and correlates them with the testicular biometric parameters and testosterone concentration in crossed Murrah x Mediterranean buffaloes. Nineteen buffaloes, with initial ages between 11 and 59 months,were submitted to fortnightly collections of semen for a period of six months. At each collection the testicular biometry and testicular echogenicity were evaluated as well as blood samples were also collected to measure the plasma testosterone levels. The data were submitted to analysis of variance by the GLM procedure, considering the age group fixed effect. The average data obtained were compared by the Duncan test, at 5% significance. There was a significant growth (P<0.05 of the scrotal circumference, which varied from 12.88±0.51 cmto 31.18±0.75 cm among animals aged 12 to 60 months, as well as testicular volume, which ranged from 30.28±17.37 to 611.96±38.69 cm³ among the animals. The echogenic intensity of the testicular parenchyma varied in pixels from 78.67±6.36 to 109.24±3.13 in animals aged 12 to 60 months respectively. In the animals with ages between 12 and 19 months was observed levels of testosterone considered being low, whereas in the animals from 20 to 21 months there was a progressive increase in the testosterone levels, which

Scaling of gene expression data allowing the comparison of different gene expression platforms

NARCIS (Netherlands)

van Ruissen, Fred; Schaaf, Gerben J.; Kool, Marcel; Baas, Frank; Ruijter, Jan M.

2008-01-01

Serial analysis of gene expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the amalgamation of the data resulting from these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce

cis sequence effects on gene expression

Directory of Open Access Journals (Sweden)

Jacobs Kevin

2007-08-01

Full Text Available Abstract Background Sequence and transcriptional variability within and between individuals are typically studied independently. The joint analysis of sequence and gene expression variation (genetical genomics provides insight into the role of linked sequence variation in the regulation of gene expression. We investigated the role of sequence variation in cis on gene expression (cis sequence effects in a group of genes commonly studied in cancer research in lymphoblastoid cell lines. We estimated the proportion of genes exhibiting cis sequence effects and the proportion of gene expression variation explained by cis sequence effects using three different analytical approaches, and compared our results to the literature. Results We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p cis sequence effects in our study, respectively. Conclusion Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.

Extracting gene expression patterns and identifying co-expressed genes from microarray data reveals biologically responsive processes

Directory of Open Access Journals (Sweden)

Paules Richard S

2007-11-01

Full Text Available Abstract Background A common observation in the analysis of gene expression data is that many genes display similarity in their expression patterns and therefore appear to be co-regulated. However, the variation associated with microarray data and the complexity of the experimental designs make the acquisition of co-expressed genes a challenge. We developed a novel method for Extracting microarray gene expression Patterns and Identifying co-expressed Genes, designated as EPIG. The approach utilizes the underlying structure of gene expression data to extract patterns and identify co-expressed genes that are responsive to experimental conditions. Results Through evaluation of the correlations among profiles, the magnitude of variation in gene expression profiles, and profile signal-to-noise ratio's, EPIG extracts a set of patterns representing co-expressed genes. The method is shown to work well with a simulated data set and microarray data obtained from time-series studies of dauer recovery and L1 starvation in C. elegans and after ultraviolet (UV or ionizing radiation (IR-induced DNA damage in diploid human fibroblasts. With the simulated data set, EPIG extracted the appropriate number of patterns which were more stable and homogeneous than the set of patterns that were determined using the CLICK or CAST clustering algorithms. However, CLICK performed better than EPIG and CAST with respect to the average correlation between clusters/patterns of the simulated data. With real biological data, EPIG extracted more dauer-specific patterns than CLICK. Furthermore, analysis of the IR/UV data revealed 18 unique patterns and 2661 genes out of approximately 17,000 that were identified as significantly expressed and categorized to the patterns by EPIG. The time-dependent patterns displayed similar and dissimilar responses between IR and UV treatments. Gene Ontology analysis applied to each pattern-related subset of co-expressed genes revealed underlying

Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

Science.gov (United States)

Diez-Caballero, Fernando; Castilla-Cortázar, Inma; Garcia-Fernandez, Maria; Puche, Juan Enrique; Diaz-Sanchez, Matias; Casares, Amelia Diaz; Aliaga-Montilla, M Aurelia; Rodriguez-Borrajo, Coronación; Gonzalez-Barón, Salvador

2006-01-01

Background Insulin-like Growth Factor-I (IGF-I) supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT) without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week) during 11 weeks. Then, rats with testicular atrophy (AT) were divided into two groups (n = 10 each): untreated rats (AT) receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g b.w.-1.day-1, sc.) for 28d. Healthy controls (CO, n = 10) were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx) were assessed. Results Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p Laron Syndrom or liver cirrhosis). PMID:16504030

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

Science.gov (United States)

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

Science.gov (United States)

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Modulation of gene expression made easy

DEFF Research Database (Denmark)

Solem, Christian; Jensen, Peter Ruhdal

2002-01-01

A new approach for modulating gene expression, based on randomization of promoter (spacer) sequences, was developed. The method was applied to chromosomal genes in Lactococcus lactis and shown to generate libraries of clones with broad ranges of expression levels of target genes. In one example...... that the method can be applied to modulating the expression of native genes on the chromosome. We constructed a series of strains in which the expression of the las operon, containing the genes pfk, pyk, and ldh, was modulated by integrating a truncated copy of the pfk gene. Importantly, the modulation affected...

Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer

DEFF Research Database (Denmark)

Hoei-Hansen, Christina E; Holm, Mette; Rajpert-De Meyts, Ewa

2003-01-01

dysgenesis, microscopic dysgenetic features were quantified in contralateral testicular biopsies in patients with a testicular germ cell tumour. Two hundred and eighty consecutive contralateral testicular biopsies from Danish patients with testicular cancer diagnosed in 1998-2001 were evaluated...... retrospectively. Two hundred and eighteen specimens were subsequently included in this study, after 63 patients who did not meet inclusion criteria had to be excluded. The presence of carcinoma in situ (which is believed to originate from transformed gonocytes) was detected in 8.7% of biopsies. The incidence...... patients, areas with immature and morphologically distorted tubules were also noted. Spermatogenesis was qualitatively normal in 51.4%, whereas 11.5% had very poor or absent spermatogenesis. It is concluded that microscopic testicular dysgenesis is a frequent feature in contralateral biopsies from patients...

Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ

DEFF Research Database (Denmark)

Rajpert-De Meyts, E; Kvist, Majbrit; Skakkebaek, N E

1996-01-01

Testicular carcinoma in situ (CIS) is the precursor of germ cell tumours in adults, except for spermatocytic seminoma. The mechanism of the progression from premalignant CIS to invasive and overt tumours is largely unknown. There are currently two main hypotheses: one is that CIS can progress dir...

Impalpable Testicular Seminoma Identified on Sonoelastography

Directory of Open Access Journals (Sweden)

Eric M. Ghiraldi

2015-09-01

Full Text Available The role of sonoelastography in diagnosing cancerous masses has increased since the advent of elastography as an ultrasound modality. Its ability to display differences in the mechanical properties of cancerous masses compared to normal surrounding tissue has shown benefit in increasing the accuracy of diagnosing malignant breast and thyroid masses and has shown early potential in accomplishing better targeted prostate biopsies. To date, the literature is limited in the number of studies describing the use of sonoelastography for testicular masses. We describe a 34-year-old man who presented with an incidental finding of an impalpable hypoechoic testicular mass on grayscale ultrasound during an infertility work-up. Sonoelastography was performed displaying intermediate testicular elastic properties. Upon frozen section of the mass during surgical exploration, classic testicular seminoma was diagnosed and subsequent radical orchiectomy was performed. We would like to use this atypical presentation of testicular seminoma to review the potential role of elastography for diagnosing testicular cancer.

Guidelines on testicular cancer

NARCIS (Netherlands)

Albers, Peter; Albrecht, Walter; Algaba, Ferran; Bokemeyer, Carsten; Cohn-Cedermark, Gabriella; Horwich, Alan; Klepp, Olbjoern; Laguna, M. Pilar; Pizzocaro, Giorgio

2005-01-01

To up-date the 2001 version of the EAU testicular cancer guidelines. A non-structured literature review until January 2005 using the MEDLINE database has been performed. Literature has been classified according to evidence-based medicine levels. Testicular cancer is a highly curable disease.

Acute testicular ischemia caused by incarcerated inguinal hernia.

Science.gov (United States)

Orth, Robert C; Towbin, Alexander J

2012-02-01

Acute testicular ischemia caused by an incarcerated inguinal hernia usually affects infants. There are few reports of diagnosis using US, and the effect of long-standing reducible hernias on testicular growth in infants and children is unknown. The objectives of this study were to determine the incidence of testicular ischemia secondary to an incarcerated inguinal hernia at scrotal sonography and to determine the effect on testicular size at diagnosis. A hospital database was used to locate scrotal sonography examinations documenting an inguinal hernia, and images were reviewed for signs of testicular ischemia. Testicular volumes were compared using the Wilcoxon signed rank test. A total of 147 patients were identified with an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%) had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and showed a statistically significant increase in ipsilateral testicular size compared to the contralateral testicle (P = 0.012). Patients without testicular ischemia did not show a significant difference in testicular size, regardless of patient age. An incarcerated inguinal hernia should be considered as a cause of acute testicular ischemia in infants younger than 6 months of age.

Using gene expression noise to understand gene regulation

NARCIS (Netherlands)

Munsky, B.; Neuert, G.; van Oudenaarden, A.

2012-01-01

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

Science.gov (United States)

Toberer, Ferdinand; Enk, Alexander; Hartschuh, Wolfgang; Grüllich, Carsten

2018-07-01

A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea; the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of cutaneous scalp tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Testicular Microlithiasis: Case Report and Literature Review

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Savić Goran

2017-09-01

Full Text Available Testicular microlithiasis is a condition characterized by the ultrasonographic findings with multiple microliths, with the prevalence of 0.6% to 9%. This is a condition of unknown etiology; however, in many cases it may be associated with cryptorchidism, Klinefelter syndrome, Down syndrome, varicocele, testicular torsion and male pseudohermaphroditism. Many retrospective studies point to the association between testicular microlithiasis and testicular cancer.

Familial testicular cancer and developmental anomalies

International Nuclear Information System (INIS)

Ondrus, D.; Kuba, D.; Chrenova, S.; Matoska, J.

1997-01-01

Familial occurrence belongs to factors followed in etiology and pathogenesis of testicular germ-cell tumors. Association with abnormal testicular development, or with other risk factors is relatively frequent. In our material 650 patients had been treated for testicular cancer in the period of 1981-1995. Familial occurrence was observed 7-times (1.08), most frequently in combination with cryptorchidism. Individual families were analyzed in details, including HLA typing. On basis of the observations the supplementation of initial examination of each patient with suspicious testicular cancer with detailed familiar history aimed also at the occurrence of urogenital developmental anomalies and tumors has been recommended. The knowledge about familial tumor occurrence in the first-degree relatives in combination with thorough testicular self-examination is being considered of great importance in the secondary prevention. (author)

Association of Torsion With Testicular Cancer: A Retrospective Study.

Science.gov (United States)

Uguz, Sami; Yilmaz, Sercan; Guragac, Ali; Topuz, Bahadır; Aydur, Emin

2016-02-01

Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported with the association of torsion in surgical specimens, and the published data remain scant on the association of torsion with testicular tumors. By retrospective medical record review, we identified 32 patients who had been diagnosed with testicular torsion, 20 of whom had undergone orchiectomy. Of these 20 patients, 2 were diagnosed with a malignancy. Our study, the largest case series to date, has shown an association between testicular torsion and testicular cancer of 6.4%. Testicular torsion is a medical emergency that usually requires surgical exploration. However, testicular malignancy has been anecdotally reported in association with torsion in surgical specimens. However, the published data remain scant on the association between torsion and the presence of testicular tumors. The present retrospective study explored the association between torsion and testicular cancer in patients with testicular torsion undergoing orchiectomy during scrotal exploration. A medical record review was performed of patients who had had a diagnosis of testicular torsion from January 2003 to February 2015. The clinicopathologic characteristics of the patients were recorded. A total of 32 patients were identified. Their mean age was 21.1 years (range, 7-39 years). All the patients had unilateral testicular torsion, which affected the left side in 17 and the right side in 15. Manual detorsion was successful in 6 patients, and 26 patients underwent emergency surgery with testicular detorsion (6 fixation surgery and 20 orchiectomy). The type of incision was scrotal in 6, inguinal in 10, and unspecified in 4. Pathologic examination of the orchiectomy specimens showed malignancy in 2 cases (seminoma and malign mixed germ cell tumor). To the best of our knowledge, the present single-center case series is the largest case series to date of

Metachronous Testicular Cancer After Orchiectomy: A Rare Case.

Science.gov (United States)

Arda, Ersan; Cakiroglu, Basri; Cetin, Gizem; Yuksel, Ilkan

2017-11-09

Testicular cancer represents approximately 1% of all cancers diagnosed in males. The prevalence of bilateral testicular germ cell tumor cases varies from 1% to 5%. Intratubular germ cell neoplasia (ITGCN) is a precursor for almost all testicular germ cell tumors (TGCT) and is one of the highest risks of developing contralateral testicular cancer. The radical orchiectomy is still preferred for the treatment of testicular cancer. However, in some cases like solitary testis, bilateral cancer or if the tumor size is under 30% percent of the testicular extent, organ-sparing surgery can be an option. There are just a few published reports of metachronous contralateral testicular cancer, developed after orchiectomy with the histopathology of the intratubular germ cell neoplasia.

Characterization of differentially expressed genes using high-dimensional co-expression networks

DEFF Research Database (Denmark)

Coelho Goncalves de Abreu, Gabriel; Labouriau, Rodrigo S.

2010-01-01

We present a technique to characterize differentially expressed genes in terms of their position in a high-dimensional co-expression network. The set-up of Gaussian graphical models is used to construct representations of the co-expression network in such a way that redundancy and the propagation...... that allow to make effective inference in problems with high degree of complexity (e.g. several thousands of genes) and small number of observations (e.g. 10-100) as typically occurs in high throughput gene expression studies. Taking advantage of the internal structure of decomposable graphical models, we...... construct a compact representation of the co-expression network that allows to identify the regions with high concentration of differentially expressed genes. It is argued that differentially expressed genes located in highly interconnected regions of the co-expression network are less informative than...

Regulation of eucaryotic gene expression

Energy Technology Data Exchange (ETDEWEB)

Brent, R.; Ptashne, M.S

1989-05-23

This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

Testicular biopsy in prepubertal boys

DEFF Research Database (Denmark)

Faure, Alice; Bouty, Aurore; O'Brien, Mike

2016-01-01

No consensus exists regarding the precise role of testicular biopsy in prepubertal boys, although it is considered useful for assessing the potential consequences of undescended testes on fertility. Current scientific knowledge indicates that surgeons should broaden indications for this procedure...... for the preservation of fertility after gonadotoxic chemotherapy - even for prepubertal boys - are emerging. Cryopreservation of testicular tissue samples for the preservation of fertility - although still an experimental method at present - is appealing in this context. In our opinion, testicular biopsy...

Endosulfan and flutamide impair testicular development in the juvenile Asian catfish, Clarias batrachus

Energy Technology Data Exchange (ETDEWEB)

Rajakumar, A.; Singh, R.; Chakrabarty, S.; Murugananthkumar, R.; Laldinsangi, C.; Prathibha, Y.; Sudhakumari, C.C.; Dutta-Gupta, A. [Department of Animal Sciences, School of Life Sciences-Centre for Advanced Studies, University of Hyderabad, P. O. Central University, Hyderabad 500046, Andhra Pradesh (India); Senthilkumaran, B., E-mail: bsksl@uohyd.ernet.in [Department of Animal Sciences, School of Life Sciences-Centre for Advanced Studies, University of Hyderabad, P. O. Central University, Hyderabad 500046, Andhra Pradesh (India)

2012-04-15

dph) to perform testicular germ cell count (histology), measurements of testosterone (T) and 11-ketotestosterone (11-KT) by enzyme immunoassay and transcript quantification by quantitative real-time PCR. In general, treatments decreased the expression of several genes including testis-related transcription factors (dmrt1, sox9a and wt1), steroidogenic enzymes (11{beta}-hsd2, 17{beta}-hsd12 and P450c17), steroidogenic acute regulatory protein and orphan nuclear receptors (nr2c1 and Ad4BP/SF-1). In contrast, the transcripts of cfGnRH and tph2 were elevated in the brain of all treated groups with maximum elevation in the endosulfan group. However, combination of endosulfan and flutamide (E + F) treatment showed minor antagonism in a few results of transcript quantification. Levels of T and 11-KT were elevated after flutamide and E + F treatments while no change was seen in the endosulfan group signifying the effect of flutamide as an androgen receptor antagonist. All the treatments modulated testis growth by decreasing the progression of differentiation of spermatogonia to spermatocytes. Based on these results, we suggest that the exposure to endosulfan and flutamide, even at low doses, impairs testicular development either directly or indirectly at the level of brain.

Morphology, sex steroid level and gene expression analysis in gonadal sex reversal of triploid female (XXX) rainbow trout (Oncorhynchus mykiss).

Science.gov (United States)

Xu, Gefeng; Huang, Tianqing; Jin, Xian; Cui, Cunhe; Li, Depeng; Sun, Cong; Han, Ying; Mu, Zhenbo

2016-02-01

In non-mammalian vertebrates, estrogens and expressions of cyp19a1 and foxl2 play critical roles in maintaining ovary differentiation and development, while dmrt1 and sox9 are male-specific genes in testicular differentiation and are highly conserved. In order to deeply understand the morphological change, sex steroids level and molecular mechanism of triploid female gonadal reversal in rainbow trout, we studied the ovary morphology, tendency of estradiol-17β (E2) and testosterone (T) levels and the relative expressions of dmrt1, cyp19a1, sox9 and foxl2 in juvenile and adult fish. Our results demonstrated that the development of triploid female gonads in rainbow trout went through arrested development, oocytes dedifferentiation, ovary reconstruction and sex reversal finally. During early gonadal development (154-334 days post-fertilization), the expressions of foxl2 and cyp19a1 increased linearly, while expressions of dmrt1 and sox9 were extremely suppressed, and E2 level was higher, while T level was lower. During the mid-to-late period of triploid female gonadal development (574-964 days post-fertilization), the expressions of dmrt1 and sox9 remained high and were very close to the quantity of diploid male genes, and T levels were even reaching diploid male plasma concentrations, while expressions of cyp19a1 and foxl2 were decreased, leading to decrease in E2 level. We realized that the development model of rainbow trout triploid female gonads was extremely rare, and the regulatory mechanism was very special. Genes involved in gonadal development and endogenous estrogens are pivotal factors in fish natural sex reversal.

Little effects of Insulin-like Growth Factor-I on testicular atrophy induced by hypoxia

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Casares Amelia

2006-02-01

Full Text Available Abstract Background Insulin-like Growth Factor-I (IGF-I supplementation restores testicular atrophy associated with advanced liver cirrhosis that is a condition of IGF-I deficiency. The aim of this work was to evaluate the effect of IGF-I in rats with ischemia-induced testicular atrophy (AT without liver disease and consequently with normal serum level of IGF-I. Methods Testicular atrophy was induced by epinephrine (1, 2 mg/Kg intra-scrotal injection five times per week during 11 weeks. Then, rats with testicular atrophy (AT were divided into two groups (n = 10 each: untreated rats (AT receiving saline sc, and AT+IGF, which were treated with IGF-I (2 μg.100 g b.w.-1.day-1, sc. for 28d. Healthy controls (CO, n = 10 were studied in parallel. Animals were sacrificed on day 29th. Hypophyso-gonadal axis, IGF-I and IGFBPs levels, testicular morphometry and histopathology, immuno-histochemical studies and antioxidant enzyme activity phospholipid hydroperoxide glutathione peroxidase (PHGPx were assessed. Results Compared to controls, AT rats displayed a reduction in testicular size and weight, with histological testicular atrophy, decreased cellular proliferation and transferrin expression, and all of these alterations were slightly improved by IGF-I at low doses. IGF-I therapy increased signifincantly steroidogenesis and PHGPx activity (p Conclusion In testicular atrophy by hypoxia, condition without IGF-I deficiency, IGF-treatment induces only partial effects. These findings suggest that IGF-I therapy appears as an appropriate treatment in hypogonadism only when this is associated to conditions of IGF-I deficiency (such as Laron Syndrom or liver cirrhosis.

Testicular Cancer—Health Professional Version

Science.gov (United States)

Most testicular cancers are germ cell tumors. Germ cell tumors are divided into seminomas and nonseminomas. Nonseminomas tend to grow and spread more quickly than seminomas. Find evidence-based information on testicular cancer treatment, screening, and statistics.

Inferring gene expression dynamics via functional regression analysis

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Leng Xiaoyan

2008-01-01

Full Text Available Abstract Background Temporal gene expression profiles characterize the time-dynamics of expression of specific genes and are increasingly collected in current gene expression experiments. In the analysis of experiments where gene expression is obtained over the life cycle, it is of interest to relate temporal patterns of gene expression associated with different developmental stages to each other to study patterns of long-term developmental gene regulation. We use tools from functional data analysis to study dynamic changes by relating temporal gene expression profiles of different developmental stages to each other. Results We demonstrate that functional regression methodology can pinpoint relationships that exist between temporary gene expression profiles for different life cycle phases and incorporates dimension reduction as needed for these high-dimensional data. By applying these tools, gene expression profiles for pupa and adult phases are found to be strongly related to the profiles of the same genes obtained during the embryo phase. Moreover, one can distinguish between gene groups that exhibit relationships with positive and others with negative associations between later life and embryonal expression profiles. Specifically, we find a positive relationship in expression for muscle development related genes, and a negative relationship for strictly maternal genes for Drosophila, using temporal gene expression profiles. Conclusion Our findings point to specific reactivation patterns of gene expression during the Drosophila life cycle which differ in characteristic ways between various gene groups. Functional regression emerges as a useful tool for relating gene expression patterns from different developmental stages, and avoids the problems with large numbers of parameters and multiple testing that affect alternative approaches.

Synthetic promoter libraries- tuning of gene expression

DEFF Research Database (Denmark)

Hammer, Karin; Mijakovic, Ivan; Jensen, Peter Ruhdal

2006-01-01

knockout and strong overexpression. However, applications such as metabolic optimization and control analysis necessitate a continuous set of expression levels with only slight increments in strength to cover a specific window around the wildtype expression level of the studied gene; this requirement can......The study of gene function often requires changing the expression of a gene and evaluating the consequences. In principle, the expression of any given gene can be modulated in a quasi-continuum of discrete expression levels but the traditional approaches are usually limited to two extremes: gene...

General Information about Testicular Cancer

Science.gov (United States)

... tumor markers are used to detect testicular cancer: Alpha-fetoprotein (AFP). Beta-human chorionic gonadotropin (β-hCG). Tumor ... tumor markers are used in staging testicular cancer : Alpha-fetoprotein (AFP) Beta-human chorionic gonadotropin (β-hCG). Lactate ...

Inguinal metastases from testicular cancer

DEFF Research Database (Denmark)

Daugaard, Gedske; Karas, Vladimir; Sommer, Peter

2006-01-01

To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease.......To evaluate the incidence of inguinal metastases in patients with testicular cancer and relapse after initial stage I disease....

Possible involvement of the glucocorticoid receptor (NR3C1) and selected NR3C1 gene variants in regulation of human testicular function

DEFF Research Database (Denmark)

Nordkap, L.; Almstrup, K.; Nielsen, J. E.

2017-01-01

Perceived stress has been associated with decreased semen quality but the mechanisms have not been elucidated. It is not known whether cortisol, the major stress hormone in humans, can act directly via receptors in the testis, and whether variants in the gene encoding the glucocorticoid receptor...... is limited, the results substantiate a suggested link between stress and testicular function. Hence this investigation should be regarded as a discovery study generating hypotheses for future studies....

Testicular Pain Associated With Minocycline Use

OpenAIRE

Kucherov, Victor; Hulbert, William; Wu, Guan

2015-01-01

Two males ages 16 and 23 years presented with new testicular pain while taking minocycline. Both patients experienced resolution of their symptoms only after minocycline discontinuation. Testicular pain with minocycline use has been previously described, however only in the setting of systemic autoimmune reactions (which were absent here). These cases represent probable rare adverse reactions to minocycline. For patients taking minocycline who experience otherwise unexplained testicular pain,...

Adaptive Evolution of Gene Expression in Drosophila.

Science.gov (United States)

Nourmohammad, Armita; Rambeau, Joachim; Held, Torsten; Kovacova, Viera; Berg, Johannes; Lässig, Michael

2017-08-08

Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Adaptive Evolution of Gene Expression in Drosophila

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Armita Nourmohammad

2017-08-01

Full Text Available Gene expression levels are important quantitative traits that link genotypes to molecular functions and fitness. In Drosophila, population-genetic studies have revealed substantial adaptive evolution at the genomic level, but the evolutionary modes of gene expression remain controversial. Here, we present evidence that adaptation dominates the evolution of gene expression levels in flies. We show that 64% of the observed expression divergence across seven Drosophila species are adaptive changes driven by directional selection. Our results are derived from time-resolved data of gene expression divergence across a family of related species, using a probabilistic inference method for gene-specific selection. Adaptive gene expression is stronger in specific functional classes, including regulation, sensory perception, sexual behavior, and morphology. Moreover, we identify a large group of genes with sex-specific adaptation of expression, which predominantly occurs in males. Our analysis opens an avenue to map system-wide selection on molecular quantitative traits independently of their genetic basis.

Genetic changes associated with testicular cancer susceptibility.

Science.gov (United States)

Pyle, Louise C; Nathanson, Katherine L

2016-10-01

Testicular germ cell tumor (TGCT) is a highly heritable cancer primarily affecting young white men. Genome-wide association studies (GWAS) have been particularly effective in identifying multiple common variants with strong contribution to TGCT risk. These loci identified through association studies have implicated multiple genes as associated with TGCT predisposition, many of which are unique among cancer types, and regulate processes such as pluripotency, sex specification, and microtubule assembly. Together these biologically plausible genes converge on pathways involved in male germ cell development and maturation, and suggest that perturbation of them confers susceptibility to TGCT, as a developmental defect of germ cell differentiation. Copyright © 2016 Elsevier Inc. All rights reserved.

Testicular dysgenesis syndrome

DEFF Research Database (Denmark)

Skakkebaek, N E; Rajpert-De Meyts, E; Main, K M

2001-01-01

Numerous reports have recently focused on various aspects of adverse trends in male reproductive health, such as the rising incidence of testicular cancer; low and probably declining semen quality; high and possibly increasing frequencies of undescended testis and hypospadias; and an apparently...... summarizes existing evidence supporting a new concept that poor semen quality, testis cancer, undescended testis and hypospadias are symptoms of one underlying entity, the testicular dysgenesis syndrome (TDS), which may be increasingly common due to adverse environmental influences. Experimental...

Dysregulated microRNA clusters in response to retinoic acid and CYP26B1 inhibitor induced testicular function in dogs.

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Vanmathy R Kasimanickam

Full Text Available Spermatogenesis is a multistep synchronized process. Diploid spermatogonia differentiate into haploid spermatozoa following mitosis, meiosis and spermiogenesis. Division and differentiation of male germ cells is achieved through the sequential expression of several genes. Numerous mRNAs in the differentiating germ cells undergo post-transcriptional and translational regulation. MiRNAs are powerful negative regulators of mRNA transcription, stability, and translation and recognize their mRNA targets through base-pairing. Retinoic acid (RA signaling is essential for spermatogenesis and testicular function. Testicular RA level is critical for RA signal transduction. This study investigated the miRNAs modulation in an RA- induced testicular environment following the administration of all-trans RA (2 µM and CYP26B1- inhibitor (1 µM compared to control. Eighty four canine mature miRNAs were analyzed and their expression signatures were distinguished using real-time PCR based array technology. Of the miRNAs analyzed, miRNA families such as miR-200 (cfa-miR-200a, cfa-miR-200b and cfa-miR-200c, Mirlet-7 (cfa-let-7a, cfa-let-7b, cfa-let-7c, cfa-let-7g and cfa-let-7f, miR-125 (cfa-miR-125a and cfa-miR-125b, miR-146 (cfa-miR-146a and cfa-miR-146b, miR-34 (cfa-miR-34a, cfa-miR-34b and cfa-miR-34c, miR-23 (cfa-miR-23a and cfa-miR-23b, cfa-miR-184, cfa-miR-214 and cfa-miR-141 were significantly up-regulated with testicular RA intervention via administration of CYP26B1 inhibitor and all-trans-RA and species of miRNA such as cfa-miR-19a, cfa-miR-29b, cfa-miR-29c, cfa-miR-101 and cfa-miR-137 were significantly down-regulated. This study explored information regarding chromosome distribution, human orthologous sequences and the interaction of target genes of miRNA families significantly distinguished in this study using prediction algorithms. This study importantly identified dysregulated miRNA species resulting from RA-induced spermatogenesis. The present

An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and Seminoma Separated by Two Decades and a Testicular Cancer Literature Review

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Dennis Andrew Buck

2017-09-01

Full Text Available Introduction: Testicular cancer is the most common malignancy in men aged 15–40 years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007 leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178: 1240–1245]. Testicular cancer presents as a painless testicular mass without transillumination. Testicular cancer is subcategorized under germ cell testicular cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90% originate in the testis, with the other 10% being extragonadal [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if a patient presents with a testicular mass and is 50 years old or older, the diagnosis of a primary lymphoma is considered until proven otherwise [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ cell testicular cancer is further divided into the subtypes of seminomatous and nonseminomatous; each presents with a unique histology and differing treatment implications. Discussion: Given the uniqueness of our patient’s metachronous second testicular primary, we sought to compare our case findings to available historic publications. We sought to address the issues of the incidence of a second primary testicular malignancy with regard to varying histology, age of incidence, and timing of a second primary testicular cancer, the presence of bowel involvement, and finally a brief discussion of testosterone replacement therapy. Conclusion: A review of our case presents several unique factors. The above varying literature has shown our patient to have met the odds of a contralateral testicular primary development in that he had a nonseminomatous primary, followed by a second testicular primary seminoma. Our patient exceeded the 15-year

An Uncommon Presentation of a Metachronous Testicular Primary Nonseminoma and Seminoma Separated by Two Decades and a Testicular Cancer Literature Review.

Science.gov (United States)

Buck, Dennis Andrew; Smith, Tristan Dean; Montana, Wilbur Nelson

2017-01-01

Testicular cancer is the most common malignancy in men aged 15-40 years [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Its incidence comprises 0.8% of all male cancers worldwide, with a mortality rate of 0.1%. The incidence has nearly doubled from 1975 to 2007 leading to the concern of environmental causes [Thomas: Am J Epidemiol 2013; 178: 1240-1245]. Testicular cancer presents as a painless testicular mass without transillumination. Testicular cancer is subcategorized under germ cell testicular cancer or sex cord-stromal tumors. Of the germ cell tumors, approximately 90% originate in the testis, with the other 10% being extragonadal [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Typically, if a patient presents with a testicular mass and is 50 years old or older, the diagnosis of a primary lymphoma is considered until proven otherwise [Bols et al.: Philadelphia, Wolters Kluwer, Lippincott Williams & Wilkins, 2011]. Germ cell testicular cancer is further divided into the subtypes of seminomatous and nonseminomatous; each presents with a unique histology and differing treatment implications. Given the uniqueness of our patient's metachronous second testicular primary, we sought to compare our case findings to available historic publications. We sought to address the issues of the incidence of a second primary testicular malignancy with regard to varying histology, age of incidence, and timing of a second primary testicular cancer, the presence of bowel involvement, and finally a brief discussion of testosterone replacement therapy. A review of our case presents several unique factors. The above varying literature has shown our patient to have met the odds of a contralateral testicular primary development in that he had a nonseminomatous primary, followed by a second testicular primary seminoma. Our patient exceeded the 15-year cumulative risk of contralateral metachronous testicular cancer of 1

Identity of M2A (D2-40) antigen and gp36 (Aggrus, T1A-2, podoplanin) in human developing testis, testicular carcinoma in situ and germ-cell tumours

DEFF Research Database (Denmark)

Sonne, Si Brask; Herlihy, Amy S; Hoei-Hansen, Christina E

2006-01-01

Testicular germ-cell tumours of young adults are derived from a pre-invasive intratubular lesion, carcinoma in situ (CIS). In a recent genome-wide gene expression screening using cDNA microarrays, we found PDPN over-expressed in CIS compared to normal adult testis. PDPN encodes podoplanin (Aggrus...... gonocytes and immature Sertoli cells, similar to the expression pattern of M2A antigen, a previously identified marker for CIS and seminoma. This reinforced our previous proposal that M2A (D2-40) antigen was identical to gp36 (podoplanin, Aggrus, T1A-2). Our findings also suggest that podoplanin has...

Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

DEFF Research Database (Denmark)

Jørgensen, N; Rajpert-De Meyts, E; Graem, N

1995-01-01

study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental......-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first......-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester...

Hypothesis: does ochratoxin A cause testicular cancer?

Science.gov (United States)

Schwartz, Gary G

2002-02-01

Little is known about the etiology of testicular cancer, which is the most common cancer among young men. Epidemiologic data point to a carcinogenic exposure in early life or in utero, but the nature of the exposure is unknown. We hypothesize that the mycotoxin, ochratoxin A, is a cause of testicular cancer. Ochratoxin A is a naturally occurring contaminant of cereals, pigmeat, and other foods and is a known genotoxic carcinogen in animals. The major features of the descriptive epidemiology of testicular cancer (a high incidence in northern Europe, increasing incidence over time, and associations with high socioeconomic status, and with poor semen quality) are all associated with exposure to ochratoxin A. Exposure of animals to ochratoxin A via the diet or via in utero transfer induces adducts in testicular DNA. We hypothesize that consumption of foods contaminated with ochratoxin A during pregnancy and/or childhood induces lesions in testicular DNA and that puberty promotes these lesions to testicular cancer. We tested the ochratoxin A hypothesis using ecologic data on the per-capita consumption of cereals, coffee, and pigmeat, the principal dietary sources of ochratoxin A. Incidence rates for testicular cancer in 20 countries were significantly correlated with the per-capita consumption of coffee and pigmeat (r = 0.49 and 0.54, p = 0.03 and 0.01). The ochratoxin A hypothesis offers a coherent explanation for much of the descriptive epidemiology of testicular cancer and suggests new avenues for analytic research.

Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

Science.gov (United States)

Xu, Pingzhen

2018-01-01

Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160

Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

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Boris P Hejblum

2015-06-01

Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

TESTICULAR CAPILLARY HEMANGIOMA: DESCRIPTION OF A CASE

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A. S. Markova

2012-01-01

Full Text Available The paper describes a clinical case of testicular capillary hemangioma in a 24-year-old man undergone a partial resection of the testis with the intraoperative morphological examination. Testicular capillary hemangioma is a rare benign tumor of a vascular origin, which can be similar to malignant testicular tumors on the clinical presentation, as well as on the imaging methods, in particular to seminoma. The intraoperative histological study can assist in avoiding organ-removing surgical interventions in diagnostically ambiguous cases if a benign testicular tumor is diagnosed.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis.

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Sonne, Si Brask; Kristensen, David Møbjerg; Novotny, Guy W; Olesen, Inge Ahlmann; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2008-04-01

Recent increases in male reproductive disorders have been linked to exposure to environmental factors leading to the testicular dysgenesis syndrome (TDS). Testicular cancer is the most severe condition in TDS and studies have shown a clear correlation between risk of testicular cancer and other components of TDS and that the geographical location of the mother during pregnancy can be a risk factor. This suggests that the dysgenesis has its origin in utero and that TDS is initiated by environmental factors, including possibly hormone-disrupting compounds that act on the mother and the developing foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from primordial germ cells or gonocytes. CIS cells and germ cell-derived cancers of the human type have so far not been described in any animal model of TDS, which could be caused by species differences in the development of the male gonad. Regardless of this, it is plausible that the dysgenesis, and hence the development of CIS cells, is a result of disturbed signalling between nurse cells and germ cells that allow embryonic germ cells to survive in the pre-pubertal and adult testis. The post-pubertal proliferation of CIS cells combined with aberrant signalling then leads to an accumulation of genetic changes in the CIS cells, which eventually results in the development of invasive testicular cancer in the adult.

Seasonal differences in the testicular transcriptome profile of free-living European beavers (Castor fiber L. determined by the RNA-Seq method.

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Iwona Bogacka

Full Text Available The European beaver (Castor fiber L. is an important free-living rodent that inhabits Eurasian temperate forests. Beavers are often referred to as ecosystem engineers because they create or change existing habitats, enhance biodiversity and prepare the environment for diverse plant and animal species. Beavers are protected in most European Union countries, but their genomic background remains unknown. In this study, gene expression patterns in beaver testes and the variations in genetic expression in breeding and non-breeding seasons were determined by high-throughput transcriptome sequencing. Paired-end sequencing in the Illumina HiSeq 2000 sequencer produced a total of 373.06 million of high-quality reads. De novo assembly of contigs yielded 130,741 unigenes with an average length of 1,369.3 nt, N50 value of 1,734, and average GC content of 46.51%. A comprehensive analysis of the testicular transcriptome revealed more than 26,000 highly expressed unigenes which exhibited the highest homology with Rattus norvegicus and Ictidomys tridecemlineatus genomes. More than 8,000 highly expressed genes were found to be involved in fundamental biological processes, cellular components or molecular pathways. The study also revealed 42 genes whose regulation differed between breeding and non-breeding seasons. During the non-breeding period, the expression of 37 genes was up-regulated, and the expression of 5 genes was down-regulated relative to the breeding season. The identified genes encode molecules which are involved in signaling transduction, DNA repair, stress responses, inflammatory processes, metabolism and steroidogenesis. Our results pave the way for further research into season-dependent variations in beaver testes.

Serum human chorionic gonadotropin is associated with angiogenesis in germ cell testicular tumors

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Avilés-Salas Alejandro

2009-08-01

Full Text Available Abstract Background Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG. hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF. Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. Methods We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP, and lactate dehydrogenase were measured prior to surgery. Vascular density (VD and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. Results Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type (p = 0.016, AFP ≥ 14.7 ng/mL (p = 0.0001, and hCG ≥ 25 mIU/mL (p = 0.0001. In multivariate analysis, the only significant VD-associated factor was hCG level (p = 0.04. When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization (p Conclusion This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.

Testicular dysgenesis syndrome and the origin of carcinoma in situ testis

DEFF Research Database (Denmark)

Sonne, Si Brask; Kristensen, David Møbjerg; Novotny, Guy W

2008-01-01

foetus, but the genetic background may also play a role. The morphological similarity of carcinoma in situ (CIS) cells (the precursor of the majority of invasive testicular cancers) with primordial germ cells and gonocytes, and overlap in expression of protein markers suggests an origin of CIS from...

Testicular teratoma, mimicking a simple testicular cyst, in an infant.

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Di Renzo, Dacia; Persico, Antonello; Sindici, Giulia; Lelli Chiesa, Pierluigi

2013-09-01

Prepubertal testicular tumors are rare, and teratoma is the second most frequent histologic type. Its typical features are those of a hard and painless scrotal mass at clinical examination, and nonhomogeneous, echoic, often with calcifications at ultrasonography. Rare but reported is the atypical presentation as a transilluminating scrotal mass, due to the presence of some internal cystic areas, detectable at ultrasonography. We report the case of an infant with a transilluminating scrotal mass, mimicking at ultrasonography and surgery a simple, fully liquid cyst, which the pathologic examination revealed to be mature cystic testicular teratoma. Copyright © 2013 Elsevier Inc. All rights reserved.

Specific immune cell and cytokine characteristics of human testicular germ cell neoplasia.

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Klein, Britta; Haggeney, Thomas; Fietz, Daniela; Indumathy, Sivanjah; Loveland, Kate L; Hedger, Mark; Kliesch, Sabine; Weidner, Wolfgang; Bergmann, Martin; Schuppe, Hans-Christian

2016-10-01

Which immune cells and cytokine profiles are characteristic for testicular germ cell neoplasia and what consequences does this have for the understanding of the related testicular immunopathology? The unique immune environment of testicular germ cell neoplasia comprises B cells and dendritic cells as well as high transcript levels of IL-6 and other B cell supporting or T helper cell type 1 (Th1)-driven cytokines and thus differs profoundly from normal testis or inflammatory lesions associated with hypospermatogenesis. T cells are known to be the major component of inflammatory infiltrates associated with either hypospermatogenesis or testicular cancer. It has previously been reported that B cells are only involved within infiltrates of seminoma samples, but this has not been investigated further. Immunohistochemical characterisation (IHC) of infiltrating immune cells and RT-qPCR-based analysis of corresponding cytokine microenvironments was performed on different testicular pathologies. Testicular biopsies, obtained from men undergoing andrological work-up of infertility or taken during surgery for testicular cancer, were used in this study. Samples were grouped as follows: (i) normal spermatogenesis (n = 18), (ii) hypospermatogenesis associated with lymphocytic infiltrates (n = 10), (iii) samples showing neoplasia [germ cell neoplasia in situ (GCNIS, n = 26) and seminoma, n = 18]. IHC was performed using antibodies against T cells (CD3+), B cells (CD20cy+), dendritic cells (CD11c+), macrophages (CD68+) and mast cells (mast cell tryptase+). Degree and compartmental localisation of immune cells throughout all groups analysed was evaluated semi-quantitatively. RT-qPCR on RNA extracted from cryo-preserved tissue samples was performed to analyse mRNA cytokine expression, specifically levels of IL-1β, IL-6, IL-17a, tumour necrosis factor (TNF)-α (pro-inflammatory), IL-10, transforming growth factor (TGF)-β1 (anti-inflammatory), IL-2, IL-12a, IL-12b

The rules of gene expression in plants: Organ identity and gene body methylation are key factors for regulation of gene expression in Arabidopsis thaliana

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Gutiérrez Rodrigo A

2008-09-01

Full Text Available Abstract Background Microarray technology is a widely used approach for monitoring genome-wide gene expression. For Arabidopsis, there are over 1,800 microarray hybridizations representing many different experimental conditions on Affymetrix™ ATH1 gene chips alone. This huge amount of data offers a unique opportunity to infer the principles that govern the regulation of gene expression in plants. Results We used bioinformatics methods to analyze publicly available data obtained using the ATH1 chip from Affymetrix. A total of 1887 ATH1 hybridizations were normalized and filtered to eliminate low-quality hybridizations. We classified and compared control and treatment hybridizations and determined differential gene expression. The largest differences in gene expression were observed when comparing samples obtained from different organs. On average, ten-fold more genes were differentially expressed between organs as compared to any other experimental variable. We defined "gene responsiveness" as the number of comparisons in which a gene changed its expression significantly. We defined genes with the highest and lowest responsiveness levels as hypervariable and housekeeping genes, respectively. Remarkably, housekeeping genes were best distinguished from hypervariable genes by differences in methylation status in their transcribed regions. Moreover, methylation in the transcribed region was inversely correlated (R2 = 0.8 with gene responsiveness on a genome-wide scale. We provide an example of this negative relationship using genes encoding TCA cycle enzymes, by contrasting their regulatory responsiveness to nitrate and methylation status in their transcribed regions. Conclusion Our results indicate that the Arabidopsis transcriptome is largely established during development and is comparatively stable when faced with external perturbations. We suggest a novel functional role for DNA methylation in the transcribed region as a key determinant

Exploring men's preferred strategies for learning about testicular disorders inclusive of testicular cancer: A qualitative descriptive study.

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Saab, Mohamad M; Landers, Margaret; Hegarty, Josephine

2017-02-01

Men's awareness of testicular disorders is lacking and their intention to seek help for testicular symptoms is sub-optimal. Studies conducted to explore and raise men's awareness of testicular disorders did not address their preferred learning strategies and failed to include men who are at risk for health inequities. The aim of this study was to explore, in-depth, the preferred strategies for learning about testicular disorders inclusive of testicular cancer among men who self-identify as heterosexual, gay, or bisexual. Maximum variation and snowball sampling were used to recruit 29 men aged 18-47 years. Participation was sought from community and youth organizations and a university in the Republic of Ireland. Semi-structured individual interviews and focus groups were conducted. Interviews were audio-recorded and transcribed verbatim. Inductive analysis of manifest content was used. Seventeen informants self-identified as heterosexual, 11 as gay, and one as bisexual. Four main categories emerged, namely: strategies to enhance awareness (television, internet, campaigns, print media), educational dos and don'ts (tailoring effective messages, drawbacks of national initiatives, ineffective learning strategies), implications of raising awareness (risks and benefits of increasing awareness), and learning among gay and bisexual men (learning needs and strategies). Future studies promoting awareness of testicular disorders should take into account men's preferred learning strategies. National campaigns should be delivered frequently and altered occasionally in order to achieve a top-up effect. Clinicians are encouraged to educate young men about the seriousness of testicular symptoms and the importance of seeking timely medical attention for any abnormalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

The functional landscape of mouse gene expression

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Zhang Wen

2004-12-01

Full Text Available Abstract Background Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such as yeast. Although the idea that tissue-specific expression is indicative of gene function in mammals is widely accepted, it has not been objectively tested nor compared with the related but distinct strategy of correlating gene co-expression as a means to predict gene function. Results We generated microarray expression data for nearly 40,000 known and predicted mRNAs in 55 mouse tissues, using custom-built oligonucleotide arrays. We show that quantitative transcriptional co-expression is a powerful predictor of gene function. Hundreds of functional categories, as defined by Gene Ontology 'Biological Processes', are associated with characteristic expression patterns across all tissues, including categories that bear no overt relationship to the tissue of origin. In contrast, simple tissue-specific restriction of expression is a poor predictor of which genes are in which functional categories. As an example, the highly conserved mouse gene PWP1 is widely expressed across different tissues but is co-expressed with many RNA-processing genes; we show that the uncharacterized yeast homolog of PWP1 is required for rRNA biogenesis. Conclusions We conclude that 'functional genomics' strategies based on quantitative transcriptional co-expression will be as fruitful in mammals as they have been in simpler organisms, and that transcriptional control of mammalian physiology is more modular than is generally appreciated. Our data and analyses provide a public resource for mammalian functional genomics.

Expression of Sox genes in tooth development.

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Kawasaki, Katsushige; Kawasaki, Maiko; Watanabe, Momoko; Idrus, Erik; Nagai, Takahiro; Oommen, Shelly; Maeda, Takeyasu; Hagiwara, Nobuko; Que, Jianwen; Sharpe, Paul T; Ohazama, Atsushi

2015-01-01

Members of the Sox gene family play roles in many biological processes including organogenesis. We carried out comparative in situ hybridization analysis of seventeen sox genes (Sox1-14, 17, 18, 21) during murine odontogenesis from the epithelial thickening to the cytodifferentiation stages. Localized expression of five Sox genes (Sox6, 9, 13, 14 and 21) was observed in tooth bud epithelium. Sox13 showed restricted expression in the primary enamel knots. At the early bell stage, three Sox genes (Sox8, 11, 17 and 21) were expressed in pre-ameloblasts, whereas two others (Sox5 and 18) showed expression in odontoblasts. Sox genes thus showed a dynamic spatio-temporal expression during tooth development.

Testicular Pain Associated With Minocycline Use

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Victor Kucherov

2015-05-01

Full Text Available Two males ages 16 and 23 years presented with new testicular pain while taking minocycline. Both patients experienced resolution of their symptoms only after minocycline discontinuation. Testicular pain with minocycline use has been previously described, however only in the setting of systemic autoimmune reactions (which were absent here. These cases represent probable rare adverse reactions to minocycline. For patients taking minocycline who experience otherwise unexplained testicular pain, a trial discontinuation of this medication should be considered.

Profiling Gene Expression in Germinating Brassica Roots.

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Park, Myoung Ryoul; Wang, Yi-Hong; Hasenstein, Karl H

2014-01-01

Based on previously developed solid-phase gene extraction (SPGE) we examined the mRNA profile in primary roots of Brassica rapa seedlings for highly expressed genes like ACT7 (actin7), TUB (tubulin1), UBQ (ubiquitin), and low expressed GLK (glucokinase) during the first day post-germination. The assessment was based on the mRNA load of the SPGE probe of about 2.1 ng. The number of copies of the investigated genes changed spatially along the length of primary roots. The expression level of all genes differed significantly at each sample position. Among the examined genes ACT7 expression was most even along the root. UBQ was highest at the tip and root-shoot junction (RS). TUB and GLK showed a basipetal gradient. The temporal expression of UBQ was highest in the MZ 9 h after primary root emergence and higher than at any other sample position. Expressions of GLK in EZ and RS increased gradually over time. SPGE extraction is the result of oligo-dT and oligo-dA hybridization and the results illustrate that SPGE can be used for gene expression profiling at high spatial and temporal resolution. SPGE needles can be used within two weeks when stored at 4 °C. Our data indicate that gene expression studies that are based on the entire root miss important differences in gene expression that SPGE is able to resolve for example growth adjustments during gravitropism.

Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene.

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Nomura, M; Tsujimura, A; Begum, N A; Matsumoto, M; Wabiko, H; Toyoshima, K; Seya, T

2000-01-01

The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3'-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8 kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein-silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46. PMID:11023821

Unstable Expression of Commonly Used Reference Genes in Rat Pancreatic Islets Early after Isolation Affects Results of Gene Expression Studies.

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Lucie Kosinová

Full Text Available The use of RT-qPCR provides a powerful tool for gene expression studies; however, the proper interpretation of the obtained data is crucially dependent on accurate normalization based on stable reference genes. Recently, strong evidence has been shown indicating that the expression of many commonly used reference genes may vary significantly due to diverse experimental conditions. The isolation of pancreatic islets is a complicated procedure which creates severe mechanical and metabolic stress leading possibly to cellular damage and alteration of gene expression. Despite of this, freshly isolated islets frequently serve as a control in various gene expression and intervention studies. The aim of our study was to determine expression of 16 candidate reference genes and one gene of interest (F3 in isolated rat pancreatic islets during short-term cultivation in order to find a suitable endogenous control for gene expression studies. We compared the expression stability of the most commonly used reference genes and evaluated the reliability of relative and absolute quantification using RT-qPCR during 0-120 hrs after isolation. In freshly isolated islets, the expression of all tested genes was markedly depressed and it increased several times throughout the first 48 hrs of cultivation. We observed significant variability among samples at 0 and 24 hrs but substantial stabilization from 48 hrs onwards. During the first 48 hrs, relative quantification failed to reflect the real changes in respective mRNA concentrations while in the interval 48-120 hrs, the relative expression generally paralleled the results determined by absolute quantification. Thus, our data call into question the suitability of relative quantification for gene expression analysis in pancreatic islets during the first 48 hrs of cultivation, as the results may be significantly affected by unstable expression of reference genes. However, this method could provide reliable information

Lifetime growth and risk of testicular cancer.

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Richiardi, Lorenzo; Vizzini, Loredana; Pastore, Guido; Segnan, Nereo; Gillio-Tos, Anna; Fiano, Valentina; Grasso, Chiara; Ciuffreda, Libero; Lista, Patrizia; Pearce, Neil; Merletti, Franco

2014-08-01

Adult height is associated with testicular cancer risk. We studied to what extent this association is explained by parental height, childhood height and age at puberty. We conducted a case-control study on germ-cell testicular cancer patients diagnosed in 1997-2008 and resident in the Province of Turin. Information was collected using mailed questionnaires in 2008-2011. Specifically, we asked for adult height (in cm), height at age 9 and 13 (compared to peers) and age at puberty (compared to peers). We also asked for paternal and maternal height (in cm) as indicators of genetic components of adult height. The analysis included 255 cases and 459 controls. Odds ratios (ORs) of testicular cancer were estimated for the different anthropometric variables. Adult height was associated with testicular cancer risk [OR: 1.16, 95% confidence interval (CI): 1.03-1.31 per 5-cm increase]. The risk of testicular cancer was only slightly increased for being taller vs. shorter than peers at age 9 (OR: 1.55, 95% CI: 0.91-2.64) or age 13 (OR: 1.26, 95% CI: 0.78-2.01), and parental height was not associated with testicular cancer risk. The OR for adult height was 1.32 (95% CI: 1.12-1.56) after adjustment for parental height. Among participants with small average parental height (testicular cancer for tall (>180 cm) vs. short (testicular cancer is likely to be explained by environmental factors affecting growth in early life, childhood and adolescence. © 2013 UICC.

Long-term health effects among testicular cancer survivors.

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Hashibe, Mia; Abdelaziz, Sarah; Al-Temimi, Mohammed; Fraser, Alison; Boucher, Kenneth M; Smith, Ken; Lee, Yuan-Chin Amy; Rowe, Kerry; Rowley, Braden; Daurelle, Micky; Holton, Avery E; VanDerslice, James; Richiardi, Lorenzo; Bishoff, Jay; Lowrance, Will; Stroup, Antoinette

2016-12-01

Testicular cancer is diagnosed at a young age and survival rates are high; thus, the long-term effects of cancer treatment need to be assessed. Our objectives are to estimate the incidence rates and determinants of late effects in testicular cancer survivors. We conducted a population-based cohort study of testicular cancer survivors, diagnosed 1991-2007, followed up for a median of 10 years. We identified 785 testicular cancer patients who survived ≥5 years and 3323 men free of cancer for the comparison group. Multivariate Cox regression analysis was used to compare the hazard ratio between the cases and the comparison group and for internal analysis among case patients. Testicular cancer survivors experienced a 24 % increase in risk of long-term health effects >5 years after diagnosis. The overall incidence rate of late effects among testicular cancer survivors was 66.3 per 1000 person years. Higher risks were observed among testicular cancer survivors for hypercholesterolemia, infertility, and orchitis. Chemotherapy and retroperitoneal lymph node dissection appeared to increase the risk of late effects. Being obese prior to cancer diagnosis appeared to be the strongest factor associated with late effects. Testicular cancer survivors were more likely to develop chronic health conditions when compared to cancer-free men. While the late effects risk was increased among testicular cancer survivors, the incidence rates of late effects after cancer diagnosis was fairly low.

Comprehensive analysis of gene expression patterns of hedgehog-related genes

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Baillie David

2006-10-01

Full Text Available Abstract Background The Caenorhabditis elegans genome encodes ten proteins that share sequence similarity with the Hedgehog signaling molecule through their C-terminal autoprocessing Hint/Hog domain. These proteins contain novel N-terminal domains, and C. elegans encodes dozens of additional proteins containing only these N-terminal domains. These gene families are called warthog, groundhog, ground-like and quahog, collectively called hedgehog (hh-related genes. Previously, the expression pattern of seventeen genes was examined, which showed that they are primarily expressed in the ectoderm. Results With the completion of the C. elegans genome sequence in November 2002, we reexamined and identified 61 hh-related ORFs. Further, we identified 49 hh-related ORFs in C. briggsae. ORF analysis revealed that 30% of the genes still had errors in their predictions and we improved these predictions here. We performed a comprehensive expression analysis using GFP fusions of the putative intergenic regulatory sequence with one or two transgenic lines for most genes. The hh-related genes are expressed in one or a few of the following tissues: hypodermis, seam cells, excretory duct and pore cells, vulval epithelial cells, rectal epithelial cells, pharyngeal muscle or marginal cells, arcade cells, support cells of sensory organs, and neuronal cells. Using time-lapse recordings, we discovered that some hh-related genes are expressed in a cyclical fashion in phase with molting during larval development. We also generated several translational GFP fusions, but they did not show any subcellular localization. In addition, we also studied the expression patterns of two genes with similarity to Drosophila frizzled, T23D8.1 and F27E11.3A, and the ortholog of the Drosophila gene dally-like, gpn-1, which is a heparan sulfate proteoglycan. The two frizzled homologs are expressed in a few neurons in the head, and gpn-1 is expressed in the pharynx. Finally, we compare the

Infertility with Testicular Cancer.

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Ostrowski, Kevin A; Walsh, Thomas J

2015-08-01

Testicular germ cell cancer is one of the most curable cancers. Most patients are treated during their reproductive years, making infertility a significant quality of life issue after successful treatment. This focused review evaluates the factors that contribute to infertility and specific fertility risks with the various testicular cancer treatments. Timing of patient discussions and current fertility treatments are reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

Early life risk factors for testicular cancer

DEFF Research Database (Denmark)

Piltoft, Johanne Spanggaard; Larsen, Signe Benzon; Dalton, Susanne Oksbjerg

2017-01-01

of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. METHODS: The study population consisted of 408 cases of testicular cancer identified by a government issued identification...... in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79-4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth......PURPOSE: One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective...

Testicular Volume: Size Does Matter

International Nuclear Information System (INIS)

Reyes Lobo, Alexander; Segovia Fuentes, Javier; Cerpa Reyes, Edgar

2011-01-01

Testicular volume is critical for semen production and, consequently, for fertility. Hence the importance of knowing the normal size ranges and the different methods for calculating size, in order to classify patients at risk and refer them for appropriate management. Ultrasound is the first-line diagnostic method for the evaluation of testicular pathology, and it is also the best tool for estimating the volume of both testicles, bearing in mind that a testicular volume below 15 cc results in fertility problems. Although there are many causes of infertility, varicocele is undoubtedly the most important of all, because of its frequency and because it is amenable to curative surgical treatment.

Testicular Metastases From Prostate Carcinoma

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Harrina Erlianti Rahardjo

2010-07-01

Full Text Available Metastasis of prostate carcinoma to the testis is seldom reported. The tumour may spread from the prostatic urethra by retrograde venous extension, arterial embolism or through direct invasion into the lymphatics and lumen of the vas deferens. Clinical manifestations of secondary testicular tumours from the prostate are most often unsuspected clinically and are instead detected incidentally during orchidectomy. Less frequently, a palpable mass is detected, which may be confused with a primary testicular neoplasm. We report a case of a 66-year-old patient with adenocarcinoma of the prostate, and a left testicular tumour that was diagnosed as metastases from prostate carcinoma after radical orchidectomy.

Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.

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Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav

2018-04-16

Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.

Methods for monitoring multiple gene expression

Energy Technology Data Exchange (ETDEWEB)

Berka, Randy [Davis, CA; Bachkirova, Elena [Davis, CA; Rey, Michael [Davis, CA

2012-05-01

The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

Methods for monitoring multiple gene expression

Energy Technology Data Exchange (ETDEWEB)

Berka, Randy; Bachkirova, Elena; Rey, Michael

2013-10-01

The present invention relates to methods for monitoring differential expression of a plurality of genes in a first filamentous fungal cell relative to expression of the same genes in one or more second filamentous fungal cells using microarrays containing Trichoderma reesei ESTs or SSH clones, or a combination thereof. The present invention also relates to computer readable media and substrates containing such array features for monitoring expression of a plurality of genes in filamentous fungal cells.

Determinants of human adipose tissue gene expression

DEFF Research Database (Denmark)

Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

2012-01-01

weight maintenance diets. For 175 genes, opposite regulation was observed during calorie restriction and weight maintenance phases, independently of variations in body weight. Metabolism and immunity genes showed inverse profiles. During the dietary intervention, network-based analyses revealed strong...... interconnection between expression of genes involved in de novo lipogenesis and components of the metabolic syndrome. Sex had a marked influence on AT expression of 88 transcripts, which persisted during the entire dietary intervention and after control for fat mass. In women, the influence of body mass index...... on expression of a subset of genes persisted during the dietary intervention. Twenty-two genes revealed a metabolic syndrome signature common to men and women. Genetic control of AT gene expression by cis signals was observed for 46 genes. Dietary intervention, sex, and cis genetic variants independently...

LINE FUSION GENES: a database of LINE expression in human genes

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Park Hong-Seog

2006-06-01

Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line

Expression analysis of MND1/GAJ, SPATA22, GAPDHS and ACR genes in testicular biopsies from non-obstructive azoospermia (NOA) patients

Czech Academy of Sciences Publication Activity Database

Dorosh, Andriy; Teplá, O.; Žatecká, Eva; Děd, Lukáš; Kočí, K.; Pěknicová, Jana

2013-01-01

Roč. 11, č. 42 (2013) ISSN 1477-7827 R&D Projects: GA ČR(CZ) GAP503/12/1834 Institutional research plan: CEZ:AV0Z50520701 Keywords : Non-obstructive azoospermia * Human test es * Biopsy * Spermatogenesis * gene expression * ICSI Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.409, year: 2013

Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko

2015-12-23

Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis-eQTLs. Expression

Familial testicular cancer in a single-centre population

NARCIS (Netherlands)

Sonneveld, DJA; Sleijfer, DT; Sijmons, RH; van der Graaf, WTA; Sluiter, WJ; Hoekstra, HJ; Schraffordt Koops, H.

Familial occurrence of testicular cancer suggests a genetic predisposition to the disease. A genetic susceptibility may also be reflected by the occurrence of bilateral testicular neoplasms and the high rates of urogenital developmental anomalies in families prone to testicular cancer. In this

Social Regulation of Gene Expression in Threespine Sticklebacks.

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Anna K Greenwood

Full Text Available Identifying genes that are differentially expressed in response to social interactions is informative for understanding the molecular basis of social behavior. To address this question, we described changes in gene expression as a result of differences in the extent of social interactions. We housed threespine stickleback (Gasterosteus aculeatus females in either group conditions or individually for one week, then measured levels of gene expression in three brain regions using RNA-sequencing. We found that numerous genes in the hindbrain/cerebellum had altered expression in response to group or individual housing. However, relatively few genes were differentially expressed in either the diencephalon or telencephalon. The list of genes upregulated in fish from social groups included many genes related to neural development and cell adhesion as well as genes with functions in sensory signaling, stress, and social and reproductive behavior. The list of genes expressed at higher levels in individually-housed fish included several genes previously identified as regulated by social interactions in other animals. The identified genes are interesting targets for future research on the molecular mechanisms of normal social interactions.

Unusual termination of the right testicular vein | Woldeyes | Anatomy ...

African Journals Online (AJOL)

The testicular veins are formed by the veins emerging from the testis and epididymis forming the pampiniform venous plexus. The right testicular vein drains into inferior vena cava and the left testicular vein to the left renal vein. Testicular veins display a great variability with regard to their number, course and sites of ...

A constructive approach to gene expression dynamics

International Nuclear Information System (INIS)

Ochiai, T.; Nacher, J.C.; Akutsu, T.

2004-01-01

Recently, experiments on mRNA abundance (gene expression) have revealed that gene expression shows a stationary organization described by a scale-free distribution. Here we propose a constructive approach to gene expression dynamics which restores the scale-free exponent and describes the intermediate state dynamics. This approach requires only one assumption: Markov property

An unusual presentation of testicular tumor

International Nuclear Information System (INIS)

Amin, M.U.; Rahan, T.; Haq, A.U.; Aftab, P.

2006-01-01

A case of testicular choriocarcinoma is reported in which blood mixed stools and haemoptysis were the presenting manifestations as the patient never told about the testicular swelling to his parents. Orchidectomy was performed but the patient presented again with massive hematemesis due to gastric perforation secondary to gastric metastasis. The size of the testis at diagnosis was approximately 12 x 7cm. This was also unusual as testicular choriocarcinoma presents as a small mass. The patient eventually died of the complications within one month of diagnosis. (author)

Evaluation of the Protective Effect of Olive Leaf Extract on Cisplatin-Induced Testicular Damage in Rats

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Rafa S. Almeer

2018-01-01

Full Text Available In the present investigation, the effect of olive leaf extract (OLE on testicular damage induced in rats by an intraperitoneal injection of cisplatin (cis-diamminedichloroplatinum (CDDP at a dose of 5 mg/kg was tested. Rats were randomly divided into 4 groups: control, CDDP, OLE, and OLE + CDDP. After 5 days of CDDP treatment, body and testicular weights, histopathological alteration, and serum male sex hormone levels were determined. In addition to the biochemical and immunohistochemical changes in the testes, CDDP caused the disorganization of germinal epithelium and apoptosis by inducing Bax and inhibiting Bcl-2 protein expression. Testicular weights, catalase, serum testosterone, testicular enzymatic (including glutathione peroxidase, glutathione reductase, and superoxide dismutase along with nonenzymatic (glutathione antioxidants, and levels of luteinizing and follicle-stimulating hormones were significantly reduced in addition to a significant increase in testicular malondialdehyde and nitrite/nitrate levels when compared with the control group. OLE treatment markedly attenuated both biochemical and histopathological changes. The reproductive beneficial effects of OLE were mediated, at least partly, by inducing the nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase 1 (HO-1 pathway.

Stably Expressed Genes Involved in Basic Cellular Functions.

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Kejian Wang

Full Text Available Stably Expressed Genes (SEGs whose expression varies within a narrow range may be involved in core cellular processes necessary for basic functions. To identify such genes, we re-analyzed existing RNA-Seq gene expression profiles across 11 organs at 4 developmental stages (from immature to old age in both sexes of F344 rats (n = 4/group; 320 samples. Expression changes (calculated as the maximum expression / minimum expression for each gene of >19000 genes across organs, ages, and sexes ranged from 2.35 to >109-fold, with a median of 165-fold. The expression of 278 SEGs was found to vary ≤4-fold and these genes were significantly involved in protein catabolism (proteasome and ubiquitination, RNA transport, protein processing, and the spliceosome. Such stability of expression was further validated in human samples where the expression variability of the homologous human SEGs was significantly lower than that of other genes in the human genome. It was also found that the homologous human SEGs were generally less subject to non-synonymous mutation than other genes, as would be expected of stably expressed genes. We also found that knockout of SEG homologs in mouse models was more likely to cause complete preweaning lethality than non-SEG homologs, corroborating the fundamental roles played by SEGs in biological development. Such stably expressed genes and pathways across life-stages suggest that tight control of these processes is important in basic cellular functions and that perturbation by endogenous (e.g., genetics or exogenous agents (e.g., drugs, environmental factors may cause serious adverse effects.

Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

NARCIS (Netherlands)

Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

1989-01-01

We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

Prognostic features and markers for testicular cancer management

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Eddy S Leman

2010-01-01

Full Text Available Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When diagnosed at early stage, testicular cancer is usually curable with a high survival rate. In the past three decades, successful multidisciplinary approaches for the management of testicular cancer have significantly increased patient survival rates. Utilization of tumor markers and accurate prognostic classification has also contributed to successful therapy. In this article, we highlight the most commonly used tumor markers and several potential "novel" markers for testicular cancer as part of the ongoing effort in biomarker research and discovery. In addition, this article also identifies several key prognostic features that have been demonstrated to play a role in predicting relapse. These features include tumor size, rete testis invasion, lymphovascular invasion, and tumor histology. Together with tumor markers, these prognostic factors should be taken into account for risk-adapted management of testicular cancer.

Validation of commonly used reference genes for sleep-related gene expression studies

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Castro Rosa MRPS

2009-05-01

Full Text Available Abstract Background Sleep is a restorative process and is essential for maintenance of mental and physical health. In an attempt to understand the complexity of sleep, multidisciplinary strategies, including genetic approaches, have been applied to sleep research. Although quantitative real time PCR has been used in previous sleep-related gene expression studies, proper validation of reference genes is currently lacking. Thus, we examined the effect of total or paradoxical sleep deprivation (TSD or PSD on the expression stability of the following frequently used reference genes in brain and blood: beta-actin (b-actin, beta-2-microglobulin (B2M, glyceraldehyde-3-phosphate dehydrogenase (GAPDH, and hypoxanthine guanine phosphoribosyl transferase (HPRT. Results Neither TSD nor PSD affected the expression stability of all tested genes in both tissues indicating that b-actin, B2M, GAPDH and HPRT are appropriate reference genes for the sleep-related gene expression studies. In order to further verify these results, the relative expression of brain derived neurotrophic factor (BDNF and glycerol-3-phosphate dehydrogenase1 (GPD1 was evaluated in brain and blood, respectively. The normalization with each of four reference genes produced similar pattern of expression in control and sleep deprived rats, but subtle differences in the magnitude of expression fold change were observed which might affect the statistical significance. Conclusion This study demonstrated that sleep deprivation does not alter the expression stability of commonly used reference genes in brain and blood. Nonetheless, the use of multiple reference genes in quantitative RT-PCR is required for the accurate results.

Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

International Nuclear Information System (INIS)

Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

2013-01-01

DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors. To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses. The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H 2 O 2 , the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased. Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to

Use of pharmacogenomics in predicting bleomycin-induced pulmonary toxicity in testicular cancer patients.

NARCIS (Netherlands)

Nuver, J; Van Zweeden, M; Holzik, ML; Meijer, C; Hoekstra, H; Suurmeijer, A; Hofstra, R; Groen, H; Sleijfer, D; Gietema, J

2004-01-01

4531 Background:Use of bleomycin, important for treatment efficacy in testicular cancer, is limited by its pulmonary toxicity. Bleomycin is mainly excreted by the kidneys, but can also be inactivated by bleomycin hydrolase (BLH). An A1450G polymorphic site in the BLH gene results in an amino acid

Stochastic gene expression in Arabidopsis thaliana.

Science.gov (United States)

Araújo, Ilka Schultheiß; Pietsch, Jessica Magdalena; Keizer, Emma Mathilde; Greese, Bettina; Balkunde, Rachappa; Fleck, Christian; Hülskamp, Martin

2017-12-14

Although plant development is highly reproducible, some stochasticity exists. This developmental stochasticity may be caused by noisy gene expression. Here we analyze the fluctuation of protein expression in Arabidopsis thaliana. Using the photoconvertible KikGR marker, we show that the protein expressions of individual cells fluctuate over time. A dual reporter system was used to study extrinsic and intrinsic noise of marker gene expression. We report that extrinsic noise is higher than intrinsic noise and that extrinsic noise in stomata is clearly lower in comparison to several other tissues/cell types. Finally, we show that cells are coupled with respect to stochastic protein expression in young leaves, hypocotyls and roots but not in mature leaves. Our data indicate that stochasticity of gene expression can vary between tissues/cell types and that it can be coupled in a non-cell-autonomous manner.

Neonatal testicular tumour presenting as an acute scrotum ...

African Journals Online (AJOL)

Juvenile granulosa cell tumour (JGCT) is a rare benign stromal cell tumour of the testis accounting for approximately 1% of all paediatric testicular tumours. Presenting primarily as a painless testicular mass, the tumour may be associated with undescended testis, hydrocele or testicular torsion. Abnormal karyotype has also ...

Deriving Trading Rules Using Gene Expression Programming

Directory of Open Access Journals (Sweden)

Adrian VISOIU

2011-01-01

Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

Using PCR to Target Misconceptions about Gene Expression

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Leslie K. Wright

2013-02-01

Full Text Available We present a PCR-based laboratory exercise that can be used with first- or second-year biology students to help overcome common misconceptions about gene expression. Biology students typically do not have a clear understanding of the difference between genes (DNA and gene expression (mRNA/protein and often believe that genes exist in an organism or cell only when they are expressed. This laboratory exercise allows students to carry out a PCR-based experiment designed to challenge their misunderstanding of the difference between genes and gene expression. Students first transform E. coli with an inducible GFP gene containing plasmid and observe induced and un-induced colonies. The following exercise creates cognitive dissonance when actual PCR results contradict their initial (incorrect predictions of the presence of the GFP gene in transformed cells. Field testing of this laboratory exercise resulted in learning gains on both knowledge and application questions on concepts related to genes and gene expression.

Secondary malignant neoplasms in testicular cancer survivors.

Science.gov (United States)

Curreri, Stephanie A; Fung, Chunkit; Beard, Clair J

2015-09-01

Testicular cancer is the most common cancer among men aged 15 to 40 years, and the incidence of testicular cancer is steadily increasing. Despite successful treatment outcomes and the rate of survival at 5 to 10 years being 95%, survivors can experience late effects of both their cancer and the treatment they received, including secondary malignant neoplasms (SMNs). We discuss the development of non-germ cell SMNs that develop after diagnosis and treatment of testicular cancer and their effect on mortality. Patients diagnosed with testicular cancer frequently choose postoperative surveillance if they are diagnosed with clinical stage I disease. These patients may experience an increased risk for developing SMNs following radiation exposure from diagnostic imaging. Similarly, radiotherapy for testicular cancer is associated with increased risks of developing both solid tumors and leukemia. Studies have reported that patients exposed to higher doses of radiation have an increased risk of developing SMNs when compared with patients who received lower doses of radiation. Patients treated with chemotherapy also experience an increased risk of developing SMNs following testicular cancer, though the risk following chemotherapy and radiation therapy combined is not well described. A large population-based study concluded that the rate ratios for both cancer-specific and all-cause mortality for SMNs among testicular cancer survivors were not significantly different from those of matched first cancers. Although it is known that patients who receive adjuvant chemotherapy or radiotherapy or who undergo routine diagnostic or follow-up imaging for a primary testicular cancer are at an increased risk for developing SMNs, the extent of this risk is largely unknown. It is critically important that research be conducted to determine this risk and its contributing factors as accurately as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

Differential gene expression during Trypanosoma cruzi metacyclogenesis

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Marco Aurelio Krieger

1999-09-01

Full Text Available The transformation of epimastigotes into metacyclic trypomastigotes involves changes in the pattern of expressed genes, resulting in important morphological and functional differences between these developmental forms of Trypanosoma cruzi. In order to identify and characterize genes involved in triggering the metacyclogenesis process and in conferring to metacyclic trypomastigotes their stage specific biological properties, we have developed a method allowing the isolation of genes specifically expressed when comparing two close related cell populations (representation of differential expression or RDE. The method is based on the PCR amplification of gene sequences selected by hybridizing and subtracting the populations in such a way that after some cycles of hybridization-amplification genes specific to a given population are highly enriched. The use of this method in the analysis of differential gene expression during T. cruzi metacyclogenesis (6 hr and 24 hr of differentiation and metacyclic trypomastigotes resulted in the isolation of several clones from each time point. Northern blot analysis showed that some genes are transiently expressed (6 hr and 24 hr differentiating cells, while others are present in differentiating cells and in metacyclic trypomastigotes. Nucleotide sequencing of six clones characterized so far showed that they do not display any homology to gene sequences available in the GeneBank.

Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon

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Hackett Perry B

2006-06-01

Full Text Available Abstract Background Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. Results Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA system that is capable of activating the expression of genes under control of a Tet response element (TRE promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. Conclusion Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene

Analysis of multiplex gene expression maps obtained by voxelation

Directory of Open Access Journals (Sweden)

Smith Desmond J

2009-04-01

Full Text Available Abstract Background Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. Results To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in

Analysis of multiplex gene expression maps obtained by voxelation.

Science.gov (United States)

An, Li; Xie, Hongbo; Chin, Mark H; Obradovic, Zoran; Smith, Desmond J; Megalooikonomou, Vasileios

2009-04-29

Gene expression signatures in the mammalian brain hold the key to understanding neural development and neurological disease. Researchers have previously used voxelation in combination with microarrays for acquisition of genome-wide atlases of expression patterns in the mouse brain. On the other hand, some work has been performed on studying gene functions, without taking into account the location information of a gene's expression in a mouse brain. In this paper, we present an approach for identifying the relation between gene expression maps obtained by voxelation and gene functions. To analyze the dataset, we chose typical genes as queries and aimed at discovering similar gene groups. Gene similarity was determined by using the wavelet features extracted from the left and right hemispheres averaged gene expression maps, and by the Euclidean distance between each pair of feature vectors. We also performed a multiple clustering approach on the gene expression maps, combined with hierarchical clustering. Among each group of similar genes and clusters, the gene function similarity was measured by calculating the average gene function distances in the gene ontology structure. By applying our methodology to find similar genes to certain target genes we were able to improve our understanding of gene expression patterns and gene functions. By applying the clustering analysis method, we obtained significant clusters, which have both very similar gene expression maps and very similar gene functions respectively to their corresponding gene ontologies. The cellular component ontology resulted in prominent clusters expressed in cortex and corpus callosum. The molecular function ontology gave prominent clusters in cortex, corpus callosum and hypothalamus. The biological process ontology resulted in clusters in cortex, hypothalamus and choroid plexus. Clusters from all three ontologies combined were most prominently expressed in cortex and corpus callosum. The experimental

A comparative gene expression database for invertebrates

Directory of Open Access Journals (Sweden)

Ormestad Mattias

2011-08-01

Full Text Available Abstract Background As whole genome and transcriptome sequencing gets cheaper and faster, a great number of 'exotic' animal models are emerging, rapidly adding valuable data to the ever-expanding Evo-Devo field. All these new organisms serve as a fantastic resource for the research community, but the sheer amount of data, some published, some not, makes detailed comparison of gene expression patterns very difficult to summarize - a problem sometimes even noticeable within a single lab. The need to merge existing data with new information in an organized manner that is publicly available to the research community is now more necessary than ever. Description In order to offer a homogenous way of storing and handling gene expression patterns from a variety of organisms, we have developed the first web-based comparative gene expression database for invertebrates that allows species-specific as well as cross-species gene expression comparisons. The database can be queried by gene name, developmental stage and/or expression domains. Conclusions This database provides a unique tool for the Evo-Devo research community that allows the retrieval, analysis and comparison of gene expression patterns within or among species. In addition, this database enables a quick identification of putative syn-expression groups that can be used to initiate, among other things, gene regulatory network (GRN projects.

Genetic Variants Contribute to Gene Expression Variability in Humans

Science.gov (United States)

Hulse, Amanda M.; Cai, James J.

2013-01-01

Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

Correction of gene expression data

DEFF Research Database (Denmark)

Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

2014-01-01

This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

Gene expression in colorectal cancer

DEFF Research Database (Denmark)

Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

2002-01-01

Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

Testicular Cancer

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... getting it in the other one? Is my son more likely to get testicular cancer if I ... and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans Nutrients and Nutritional ...

Multiscale Embedded Gene Co-expression Network Analysis.

Directory of Open Access Journals (Sweden)

Won-Min Song

2015-11-01

Full Text Available Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3, the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA by: i introducing quality control of co-expression similarities, ii parallelizing embedded network construction, and iii developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs. We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA. MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Multiscale Embedded Gene Co-expression Network Analysis.

Science.gov (United States)

Song, Won-Min; Zhang, Bin

2015-11-01

Gene co-expression network analysis has been shown effective in identifying functional co-expressed gene modules associated with complex human diseases. However, existing techniques to construct co-expression networks require some critical prior information such as predefined number of clusters, numerical thresholds for defining co-expression/interaction, or do not naturally reproduce the hallmarks of complex systems such as the scale-free degree distribution of small-worldness. Previously, a graph filtering technique called Planar Maximally Filtered Graph (PMFG) has been applied to many real-world data sets such as financial stock prices and gene expression to extract meaningful and relevant interactions. However, PMFG is not suitable for large-scale genomic data due to several drawbacks, such as the high computation complexity O(|V|3), the presence of false-positives due to the maximal planarity constraint, and the inadequacy of the clustering framework. Here, we developed a new co-expression network analysis framework called Multiscale Embedded Gene Co-expression Network Analysis (MEGENA) by: i) introducing quality control of co-expression similarities, ii) parallelizing embedded network construction, and iii) developing a novel clustering technique to identify multi-scale clustering structures in Planar Filtered Networks (PFNs). We applied MEGENA to a series of simulated data and the gene expression data in breast carcinoma and lung adenocarcinoma from The Cancer Genome Atlas (TCGA). MEGENA showed improved performance over well-established clustering methods and co-expression network construction approaches. MEGENA revealed not only meaningful multi-scale organizations of co-expressed gene clusters but also novel targets in breast carcinoma and lung adenocarcinoma.

Vitamin D metabolism and effects on pluripotency genes and cell differentiation in testicular germ cell tumors in vitro and in vivo

DEFF Research Database (Denmark)

Blomberg Jensen, Martin; Jørgensen, Anne; Nielsen, John Erik

2012-01-01

and express pluripotency factors (NANOG/OCT4). Vitamin D (VD) is metabolized in the testes, and here, we examined VD metabolism in TGCT differentiation and pluripotency regulation. We established that the VD receptor (VDR) and VD-metabolizing enzymes are expressed in human fetal germ cells, CIS, and invasive......) treatment in vivo. These novel findings show that VD metabolism is involved in the mesodermal transition during differentiation of cancer cells with embryonic stem cell characteristics, which points to a function for VD during early embryonic development and possibly in the pathogenesis of TGCTs.......Testicular germ cell tumors (TGCTs) are classified as either seminomas or nonseminomas. Both tumors originate from carcinoma in situ (CIS) cells, which are derived from transformed fetal gonocytes. CIS, seminoma, and the undifferentiated embryonal carcinoma (EC) retain an embryonic phenotype...

Analysis of Gene Expression Profiles of Microdissected Cell Populations Indicates that Testicular Carcinoma In situ Is an Arrested Gonocyte

DEFF Research Database (Denmark)

Sonne, S. B.; Almstrup, K.; Dalgaard, M.

2009-01-01

samples of each tissue type were used for the analyses. Unique expression patterns for these developmentally very related cell types revealed that CIS cells were very similar to gonocytes because only five genes distinguished these two cell types. We did not find indications that CIS was derived from....... speculate that disturbed development of somatic cells in the fetal testis may play a role in allowing undifferentiated cells to survive in the postnatal testes. The further development of CIS into invasive germ cell tumors may depend on signals from their postpubertal niche of somatic cells, including...

Testicular biopsy in psittacine birds (Psittaciformes): comparative evaluation of testicular reproductive status by endoscopic, histologic, and cytologic examination.

Science.gov (United States)

Hänse, Maria; Krautwald-Junghanns, Maria-Elisabeth; Reitemeier, Susanne; Einspanier, Almuth; Schmidt, Volker

2013-12-01

Knowledge of the reproductive cycle of male parrots is important for examining the male genital tract and for successful breeding, especially of endangered species. To evaluate different diagnostic methods and criteria concerning the classification of reproductive stages, we examined 20 testicular samples obtained at necropsy in psittacine birds of different species and testicular biopsy samples collected from 9 cockatiels (Nymphicus hollandicus) and 7 rose-ringed parakeets (Psittacula krameri) by endoscopy 4 times over a 12-month period. The testicular reproductive status was assessed histologically and then compared with the macroscopic appearance of the testicles and cytologic results. The histologic examination was nondiagnostic in 19 of 59 testicular biopsy samples. By contrast, the cytologic preparations were diagnostic in 57 of 59 biopsy samples. The results of the cytologic examination coincided with the histologic results in 34 of 38 biopsy samples and 18 of 20 necropsy samples. Macroscopic parameters displayed some differences between reproductive stages but provided an unreliable indication of the reproductive status. These results suggest that microscopic examination of a testicular biopsy sample is a reliable method for evaluating the reproductive status of male parrots and is preferable to the macroscopic evaluation of the testicle. Cytologic examination provides fast preliminary results, even when the histologic preparation is not sufficient for evaluation, but results may be erroneous. Thus, a combination of histologic and cytologic examination is recommended for evaluating testicular reproductive status.

Vascular Gene Expression: A Hypothesis

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Angélica Concepción eMartínez-Navarro

2013-07-01

Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

GSEH: A Novel Approach to Select Prostate Cancer-Associated Genes Using Gene Expression Heterogeneity.

Science.gov (United States)

Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun

2018-01-01

When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.

The evolution of gene expression in primates

OpenAIRE

Tashakkori Ghanbarian, Avazeh

2015-01-01

The evolution of a gene’s expression profile is commonly assumed to be independent of its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between expression of neighboring genes in extant taxa. Indeed, in all eukaryotic genomes, genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their e...

Testicular cancer knowledge among deaf and hearing men.

Science.gov (United States)

Sacks, Loren; Nakaji, Melanie; Harry, Kadie M; Oen, Marcia; Malcarne, Vanessa L; Sadler, Georgia Robins

2013-09-01

Testicular cancer typically affects young and middle-aged men. An educational video about prostate and testicular cancer was created in American Sign Language, with English open captioning and voice overlay, so that it could be viewed by audiences of diverse ages and hearing characteristics. This study recruited young Deaf (n = 85) and hearing (n = 90) adult males to help evaluate the educational value of the testicular cancer portion of this video. Participants completed surveys about their general, testicular, and total cancer knowledge before and after viewing the video. Although hearing men had higher pre-test scores than Deaf men, both Deaf and hearing men demonstrated significant increases in General, Testicular, and Total Cancer Knowledge scores after viewing the intervention video. Overall, results demonstrate the value of the video to Deaf and hearing men.

Onco-testicular sperm extraction: birth of a healthy baby after fertility preservation in synchronous bilateral testicular cancer and azoospermia.

Science.gov (United States)

Roque, M; Sampaio, M; Salles, P G de Oliveira; Geber, S

2015-05-01

Testicular germ cell tumours (TGCT) represent 1%-1.5% of all male neoplasms, and they have the highest prevalence among men between 15 and 35 years old. Synchronous bilateral disease is a rare presentation, and the ratio of metachronous to synchronous bilateral disease is about 4 : 1. Several studies have suggested a correlation between male infertility and testicular cancer, with a 20-fold increase in the incidence of testicular cancer in infertile patients compared with the general population. At the time of diagnosis, 50%-75% of patients with unilateral TGCT present with subfertility; almost 13% of the patients are azoospermic before treatment, and up to two-thirds of patients become azoospermic following adjuvant cancer therapies. Therefore, fertility preservation should be considered in all oncological treatments. The only available option to preserve the reproductive potential in azoospermic patients with testicular cancer is to perform an onco-testicular sperm extraction (onco-TESE) before cancer treatment. In this paper, we describe a rare case of a patient with synchronous bilateral testicular cancer and azoospermia who was submitted to onco-TESE, sperm cryopreservation, and which was followed by the delivery of a healthy baby after intracytoplasmic sperm injection (ICSI), emphasising the importance of fertility preservation in oncology patients. © 2014 Blackwell Verlag GmbH.

Treatment-associated leukemia following testicular cancer

NARCIS (Netherlands)

Travis, LB; Andersson, M; Gospodarowicz, M; van Leeuwen, FE; Bergfeldt, K; Lynch, CF; Curtis, RE; Kohler, BA; Wiklund, T; Storm, H; Holowaty, E; Hall, P; Pukkala, E; Sleijfer, DT; Clarke, EA; Boice, JD; Stovall, M; Gilbert, E

2000-01-01

Background: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. Methods: Within a

Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

International Nuclear Information System (INIS)

Salem, Tamer Z.; Zhang, Fengrui; Thiem, Suzanne M.

2013-01-01

Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

Reduced expression of Autographa californica nucleopolyhedrovirus ORF34, an essential gene, enhances heterologous gene expression

Energy Technology Data Exchange (ETDEWEB)

Salem, Tamer Z. [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbial Molecular Biology, AGERI, Agricultural Research Center, Giza 12619 (Egypt); Division of Biomedical Sciences, Zewail University, Zewail City of Science and Technology, Giza 12588 (Egypt); Zhang, Fengrui [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Thiem, Suzanne M., E-mail: smthiem@msu.edu [Department of Entomology, Michigan State University, East Lansing, MI 48824 (United States); Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824 (United States)

2013-01-20

Autographa californica multiple nucleopolyhedrovirus ORF34 is part of a transcriptional unit that includes ORF32, encoding a viral fibroblast growth factor (FGF) and ORF33. We identified ORF34 as a candidate for deletion to improve protein expression in the baculovirus expression system based on enhanced reporter gene expression in an RNAi screen of virus genes. However, ORF34 was shown to be an essential gene. To explore ORF34 function, deletion (KO34) and rescue bacmids were constructed and characterized. Infection did not spread from primary KO34 transfected cells and supernatants from KO34 transfected cells could not infect fresh Sf21 cells whereas the supernatant from the rescue bacmids transfection could recover the infection. In addition, budded viruses were not observed in KO34 transfected cells by electron microscopy, nor were viral proteins detected from the transfection supernatants by western blots. These demonstrate that ORF34 is an essential gene with a possible role in infectious virus production.

Testicular cancer: addressing the psychosexual issues.

LENUS (Irish Health Repository)

Moore, Annamarie

2012-01-31

Testicular cancer is the most common malignancy in men aged 15-35 years and predominantly occurs at a time in a man\\'s life when important decisions about marriage, starting a family and a professional career are being made. While treatments for testicular cancer are very successful, they can have a major impact on the person\\'s sexuality and sense of self. The focus of this article is on exploring the impact of cancer treatments for testicular cancer on men\\'s sexuality and how nurses can respond to their concerns in a sensitive and informed manner.

Widespread ectopic expression of olfactory receptor genes

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Yanai Itai

2006-05-01

Full Text Available Abstract Background Olfactory receptors (ORs are the largest gene family in the human genome. Although they are expected to be expressed specifically in olfactory tissues, some ectopic expression has been reported, with special emphasis on sperm and testis. The present study systematically explores the expression patterns of OR genes in a large number of tissues and assesses the potential functional implication of such ectopic expression. Results We analyzed the expression of hundreds of human and mouse OR transcripts, via EST and microarray data, in several dozens of human and mouse tissues. Different tissues had specific, relatively small OR gene subsets which had particularly high expression levels. In testis, average expression was not particularly high, and very few highly expressed genes were found, none corresponding to ORs previously implicated in sperm chemotaxis. Higher expression levels were more common for genes with a non-OR genomic neighbor. Importantly, no correlation in expression levels was detected for human-mouse orthologous pairs. Also, no significant difference in expression levels was seen between intact and pseudogenized ORs, except for the pseudogenes of subfamily 7E which has undergone a human-specific expansion. Conclusion The OR superfamily as a whole, show widespread, locus-dependent and heterogeneous expression, in agreement with a neutral or near neutral evolutionary model for transcription control. These results cannot reject the possibility that small OR subsets might play functional roles in different tissues, however considerable care should be exerted when offering a functional interpretation for ectopic OR expression based only on transcription information.

Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

Science.gov (United States)

Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

2013-01-01

The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology.

Science.gov (United States)

Pérez, Cecilia V; Gómez, Leticia G; Gualdoni, Gisela S; Lustig, Livia; Rabinovich, Gabriel A; Guazzone, Vanesa A

2015-07-30

Galectin-1 (Gal-1), a proto-type member of galectin family, is highly expressed in immune privileged sites, including the testis. However, in spite of considerable progress the relevance of endogenous and exogenous Gal-1 in testis pathophysiology have not yet been explored. Here we evaluated the in vivo roles of Gal-1 in experimental autoimmune orchitis (EAO), a well-established model of autoimmune testicular inflammation associated with subfertility and infertility. A significant reduction in the incidence and severity of EAO was observed in mice genetically deficient in Gal-1 (Lgals1(-/-)) versus wild-type (WT) mice. Testicular histopathology revealed the presence of multifocal testicular damage in WT mice characterized by an interstitial mononuclear cell infiltrate and different degrees of germ cell sloughing of seminiferous tubules. TUNEL assay and assessment of active caspase-3 expression, revealed the prevalence of apoptotic spermatocytes mainly localized in the adluminal compartment of seminiferous tubules in EAO mice. A significant increased number of TUNEL-positive germ cells was detected in EAO testis from WT compared with Lgals1(-/-) mice. In contrast, exogenous administration of recombinant Gal-1 to WT mice undergoing EAO attenuated the severity of the disease. Our results unveil a dual role of endogenous versus exogenous Gal-1 in the control of autoimmune testis inflammation.

Dynamic association rules for gene expression data analysis.

Science.gov (United States)

Chen, Shu-Chuan; Tsai, Tsung-Hsien; Chung, Cheng-Han; Li, Wen-Hsiung

2015-10-14

The purpose of gene expression analysis is to look for the association between regulation of gene expression levels and phenotypic variations. This association based on gene expression profile has been used to determine whether the induction/repression of genes correspond to phenotypic variations including cell regulations, clinical diagnoses and drug development. Statistical analyses on microarray data have been developed to resolve gene selection issue. However, these methods do not inform us of causality between genes and phenotypes. In this paper, we propose the dynamic association rule algorithm (DAR algorithm) which helps ones to efficiently select a subset of significant genes for subsequent analysis. The DAR algorithm is based on association rules from market basket analysis in marketing. We first propose a statistical way, based on constructing a one-sided confidence interval and hypothesis testing, to determine if an association rule is meaningful. Based on the proposed statistical method, we then developed the DAR algorithm for gene expression data analysis. The method was applied to analyze four microarray datasets and one Next Generation Sequencing (NGS) dataset: the Mice Apo A1 dataset, the whole genome expression dataset of mouse embryonic stem cells, expression profiling of the bone marrow of Leukemia patients, Microarray Quality Control (MAQC) data set and the RNA-seq dataset of a mouse genomic imprinting study. A comparison of the proposed method with the t-test on the expression profiling of the bone marrow of Leukemia patients was conducted. We developed a statistical way, based on the concept of confidence interval, to determine the minimum support and minimum confidence for mining association relationships among items. With the minimum support and minimum confidence, one can find significant rules in one single step. The DAR algorithm was then developed for gene expression data analysis. Four gene expression datasets showed that the proposed

Gene expression in periodontal tissues following treatment

Directory of Open Access Journals (Sweden)

Eisenacher Martin

2008-07-01

Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

Association of Down's syndrome and testicular cancer.

Science.gov (United States)

Dieckmann, K P; Rübe, C; Henke, R P

1997-05-01

We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.

Gene expression profiles in skeletal muscle after gene electrotransfer

DEFF Research Database (Denmark)

Hojman, Pernille; Zibert, John R; Gissel, Hanne

2007-01-01

BACKGROUND: Gene transfer by electroporation (DNA electrotransfer) to muscle results in high level long term transgenic expression, showing great promise for treatment of e.g. protein deficiency syndromes. However little is known about the effects of DNA electrotransfer on muscle fibres. We have...... caused down-regulation of structural proteins e.g. sarcospan and catalytic enzymes. Injection of DNA induced down-regulation of intracellular transport proteins e.g. sentrin. The effects on muscle fibres were transient as the expression profiles 3 weeks after treatment were closely related......) followed by a long low voltage pulse (LV, 100 V/cm, 400 ms); a pulse combination optimised for efficient and safe gene transfer. Muscles were transfected with green fluorescent protein (GFP) and excised at 4 hours, 48 hours or 3 weeks after treatment. RESULTS: Differentially expressed genes were...

Comparative gene expression between two yeast species

Directory of Open Access Journals (Sweden)

Guan Yuanfang

2013-01-01

Full Text Available Abstract Background Comparative genomics brings insight into sequence evolution, but even more may be learned by coupling sequence analyses with experimental tests of gene function and regulation. However, the reliability of such comparisons is often limited by biased sampling of expression conditions and incomplete knowledge of gene functions across species. To address these challenges, we previously systematically generated expression profiles in Saccharomyces bayanus to maximize functional coverage as compared to an existing Saccharomyces cerevisiae data repository. Results In this paper, we take advantage of these two data repositories to compare patterns of ortholog expression in a wide variety of conditions. First, we developed a scalable metric for expression divergence that enabled us to detect a significant correlation between sequence and expression conservation on the global level, which previous smaller-scale expression studies failed to detect. Despite this global conservation trend, between-species gene expression neighborhoods were less well-conserved than within-species comparisons across different environmental perturbations, and approximately 4% of orthologs exhibited a significant change in co-expression partners. Furthermore, our analysis of matched perturbations collected in both species (such as diauxic shift and cell cycle synchrony demonstrated that approximately a quarter of orthologs exhibit condition-specific expression pattern differences. Conclusions Taken together, these analyses provide a global view of gene expression patterns between two species, both in terms of the conditions and timing of a gene's expression as well as co-expression partners. Our results provide testable hypotheses that will direct future experiments to determine how these changes may be specified in the genome.

A possible new syndrome with growth-hormone secreting pituitary adenoma, colonic polyposis, lipomatosis, lentigines and renal carcinoma in association with familial testicular germ cell malignancy: A case report

Directory of Open Access Journals (Sweden)

Mai Phuong L

2007-03-01

Full Text Available Abstract Background Germ-cell testicular cancer has not been definitively linked to any known hereditary cancer susceptibility disorder. Familial testicular cancer in the presence of other findings in affected and unaffected family members might indicate a previously-unidentified hereditary cancer syndrome. Case presentation The patient was diagnosed with a left testicular seminoma at age 28, and treated with left orchiectomy followed by adjuvant cobalt radiation. His family history is significant for testicular seminoma in his son, bladder cancer in his sister, and lipomatosis in his father. His evaluation as part of an etiologic study of familial testicular cancer revealed multiple colon polyps (adenomatous, hyperplastic, and hamartomatous first found in his 50 s, multiple lipomas, multiple hyperpigmented skin lesions, left kidney cancer diagnosed at age 64, and a growth-hormone producing pituitary adenoma with associated acromegaly diagnosed at age 64. The patient underwent genetic testing for Cowden syndrome (PTEN gene, Carney complex (PRKAR1A gene, and multiple endocrine neoplasia syndrome type 1 (MEN1 gene; no deleterious mutations were identified. Discussion The constellation of benign and malignant neoplasms in the context of this patient's familial testicular cancer raised the possibility that these might be manifestations of a known hereditary susceptibility cancer syndrome; however, genetic testing for the three syndromes that were most likely to explain these findings did not show any mutation. Alternatively, this family's phenotype might represent a novel neoplasm susceptibility disorder. This possibility cannot be evaluated definitively on the basis of a single case report; additional observations and studies are necessary to investigate this hypothesis further.

The clinical utility of testicular prosthesis placement in children with genital and testicular disorders

Science.gov (United States)

2014-01-01

Testicular prosthesis placement is a useful important adjunctive reconstructive therapy for managing children with testicular loss or absence. Though these prostheses are functionless, experience has shown that they are extremely helpful in creating a more normal male body image and in preventing/relieving psychological stress in males with a missing testicle. With attention to details of implant technique, excellent cosmetic results can be anticipated in simulating a normal appearing scrotum. PMID:26816795

Attenuation of the cyproterone acetate-induced testicular hypofunction by a novel nutraceutical lycopene: a genomic approach.

Science.gov (United States)

Tripathy, A; Ghosh, A; Dey, A; Pakhira, B P; Ghosh, D

2017-10-01

This study was designed to explore the cyproterone acetate (CPA)-induced andrological hypofunction and its correction by oral administration of lycopene. In this concern, spermatogenic, biochemical, histological and genomic profiles were studied. Cyproterone acetate administration for 1 month helped to develop infertile model rats. A significant recovery was noted in sperm motility, sperm count, sperm viability, hypo-osmotic swelling tail-coiled spermatozoa; activities of testicular ∆ 5 , 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, catalase (CAT) and superoxide dismutase (SOD); and levels of conjugated diene (CD), malondialdehyde (MDA), testicular cholesterol and serum testosterone after the administration of lycopene at 1.5 mg/0.5 ml Tween-80/100 g body weight/day for last 1 month to infertile model rats. Simultaneously, qRT-PCR study of Bax, Bcl-2, caspase-3, ∆ 5 , 3β-HSD and 17β-HSD genes in testicular tissue showed a significant rectification towards the control in CPA-pre-treated cum CPA-lycopene-cotreated rats. Side-by-side histological and histometric studies showed a significant correction in qualitative analysis of spermatogenesis and seminiferous tubular diameter (STD) in CPA-pre-treated cum CPA-lycopene-cotreated rats. Lycopene showed outstanding efficacy in the management of CPA-induced testicular hypofunction with special reference to correction in oxidative stress-induced testicular apoptosis at genomic level. © 2016 Blackwell Verlag GmbH.

Interactive visualization of gene regulatory networks with associated gene expression time series data

NARCIS (Netherlands)

Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.

2008-01-01

We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

Serial analysis of gene expression (SAGE)

NARCIS (Netherlands)

van Ruissen, Fred; Baas, Frank

2007-01-01

In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE

An Interactive Database of Cocaine-Responsive Gene Expression

Directory of Open Access Journals (Sweden)

Willard M. Freeman

2002-01-01

Full Text Available The postgenomic era of large-scale gene expression studies is inundating drug abuse researchers and many other scientists with findings related to gene expression. This information is distributed across many different journals, and requires laborious literature searches. Here, we present an interactive database that combines existing information related to cocaine-mediated changes in gene expression in an easy-to-use format. The database is limited to statistically significant changes in mRNA or protein expression after cocaine administration. The Flash-based program is integrated into a Web page, and organizes changes in gene expression based on neuroanatomical region, general function, and gene name. Accompanying each gene is a description of the gene, links to the original publications, and a link to the appropriate OMIM (Online Mendelian Inheritance in Man entry. The nature of this review allows for timely modifications and rapid inclusion of new publications, and should help researchers build second-generation hypotheses on the role of gene expression changes in the physiology and behavior of cocaine abuse. Furthermore, this method of organizing large volumes of scientific information can easily be adapted to assist researchers in fields outside of drug abuse.

Global incidence and outcome of testicular cancer

Science.gov (United States)

Shanmugalingam, Thurkaa; Soultati, Aspasia; Chowdhury, Simon; Rudman, Sarah; Van Hemelrijck, Mieke

2013-01-01

Background Testicular cancer is a rare tumor type accounting for 1% of malignancies in men. It is, however, the most common cancer in young men in Western populations. The incidence of testicular cancer is increasing globally, although a decline in mortality rates has been reported in Western countries. It is important to identify whether the variations in trends observed between populations are linked to genetic or environmental factors. Methods Age-standardized incidence rates and age-standardized mortality rates for testicular cancer were obtained for men of all ages in ten countries from the Americas, Asia, Europe, and Oceania using the Cancer Incidence in Five Continents (CI5plus) and World Health Organization (WHO) mortality databases. The annual percent change was calculated using Joinpoint regression to assess temporal changes between geographical regions. Results Testicular cancer age-standardized incidence rates are highest in New Zealand (7.8), UK (6.3), Australia (6.1), Sweden (5.6), USA (5.2), Poland (4.9), and Spain (3.8) per 100,000 men. India, China, and Colombia had the lowest incidence (0.5, 1.3, and 2.2, respectively) per 100,000 men. The annual percent changes for overall testicular cancer incidence significantly increased in the European countries Sweden 2.4%, (2.2; 2.6); UK 2.9%, (2.2; 3.6); and Spain 5.0%, (1.7; 8.4), Australia 3.0%, (2.2; 3.7), and China 3.5%, (1.9; 5.1). India had the lowest overall testicular cancer incidence −1.7%, (−2.5; −0.8). Annual percent changes for overall testicular cancer mortality rates were decreasing in all study populations, with the greatest decline observed in Sweden −4.2%, (−4.8; −3.6) and China −4.9%, (−6.5; −3.3). Conclusion Testicular cancer is increasing in incidence in many countries; however, mortality rates remain low and most men are cured. An understanding of the risks and long-term side effects of treatment are important in managing men with this disease. PMID:24204171

CDX2 gene expression in acute lymphoblastic leukemia

International Nuclear Information System (INIS)

Arnaoaut, H.H.; Mokhtar, D.A.; Samy, R.M.; Omar, Sh.A.; Khames, S.A.

2014-01-01

CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR) to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL) at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD) on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

Identification of reference genes in human myelomonocytic cells for gene expression studies in altered gravity.

Science.gov (United States)

Thiel, Cora S; Hauschild, Swantje; Tauber, Svantje; Paulsen, Katrin; Raig, Christiane; Raem, Arnold; Biskup, Josefine; Gutewort, Annett; Hürlimann, Eva; Unverdorben, Felix; Buttron, Isabell; Lauber, Beatrice; Philpot, Claudia; Lier, Hartwin; Engelmann, Frank; Layer, Liliana E; Ullrich, Oliver

2015-01-01

Gene expression studies are indispensable for investigation and elucidation of molecular mechanisms. For the process of normalization, reference genes ("housekeeping genes") are essential to verify gene expression analysis. Thus, it is assumed that these reference genes demonstrate similar expression levels over all experimental conditions. However, common recommendations about reference genes were established during 1 g conditions and therefore their applicability in studies with altered gravity has not been demonstrated yet. The microarray technology is frequently used to generate expression profiles under defined conditions and to determine the relative difference in expression levels between two or more different states. In our study, we searched for potential reference genes with stable expression during different gravitational conditions (microgravity, normogravity, and hypergravity) which are additionally not altered in different hardware systems. We were able to identify eight genes (ALB, B4GALT6, GAPDH, HMBS, YWHAZ, ABCA5, ABCA9, and ABCC1) which demonstrated no altered gene expression levels in all tested conditions and therefore represent good candidates for the standardization of gene expression studies in altered gravity.

Testicular Cancer

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... of skin behind the penis. You can get cancer in one or both testicles. Testicular cancer mainly affects young men between the ages of ... undescended testicle Have a family history of the cancer Symptoms include pain, swelling, or lumps in your ...

Inferring gene networks from discrete expression data

KAUST Repository

Zhang, L.

2013-07-18

The modeling of gene networks from transcriptional expression data is an important tool in biomedical research to reveal signaling pathways and to identify treatment targets. Current gene network modeling is primarily based on the use of Gaussian graphical models applied to continuous data, which give a closedformmarginal likelihood. In this paper,we extend network modeling to discrete data, specifically data from serial analysis of gene expression, and RNA-sequencing experiments, both of which generate counts of mRNAtranscripts in cell samples.We propose a generalized linear model to fit the discrete gene expression data and assume that the log ratios of the mean expression levels follow a Gaussian distribution.We restrict the gene network structures to decomposable graphs and derive the graphs by selecting the covariance matrix of the Gaussian distribution with the hyper-inverse Wishart priors. Furthermore, we incorporate prior network models based on gene ontology information, which avails existing biological information on the genes of interest. We conduct simulation studies to examine the performance of our discrete graphical model and apply the method to two real datasets for gene network inference. © The Author 2013. Published by Oxford University Press. All rights reserved.

GESTATIONAL AGE AT BIRTH AND RISK OF TESTICULAR CANCER

Science.gov (United States)

Crump, Casey; Sundquist, Kristina; Winkleby, Marilyn A.; Sieh, Weiva; Sundquist, Jan

2011-01-01

Most testicular germ cell tumors originate from carcinoma in situ cells in fetal life, possibly related to sex hormone imbalances in early pregnancy. Previous studies of association between gestational age at birth and testicular cancer have yielded discrepant results and have not examined extreme preterm birth. Our objective was to determine whether low gestational age at birth is independently associated with testicular cancer in later life. We conducted a national cohort study of 354,860 men born in Sweden in 1973–1979, including 19,214 born preterm (gestational age testicular cancer incidence through 2008. A total of 767 testicular cancers (296 seminomas and 471 nonseminomatous germ cell tumors) were identified in 11.2 million person-years of follow-up. Extreme preterm birth was associated with an increased risk of testicular cancer (hazard ratio 3.95; 95% CI, 1.67–9.34) after adjusting for other perinatal factors, family history of testicular cancer, and cryptorchidism. Only five cases (three seminomas and two nonseminomas) occurred among men born extremely preterm, limiting the precision of risk estimates. No association was found between later preterm birth, post-term birth, or low or high fetal growth and testicular cancer. These findings suggest that extreme but not later preterm birth may be independently associated with testicular cancer in later life. They are based on a small number of cases and will need confirmation in other large cohorts. Elucidation of the key prenatal etiologic factors may potentially lead to preventive interventions in early life. PMID:22314417

Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

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Yu Zhang

2013-12-01

Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

Studying the Complex Expression Dependences between Sets of Coexpressed Genes

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Mario Huerta

2014-01-01

Full Text Available Organisms simplify the orchestration of gene expression by coregulating genes whose products function together in the cell. The use of clustering methods to obtain sets of coexpressed genes from expression arrays is very common; nevertheless there are no appropriate tools to study the expression networks among these sets of coexpressed genes. The aim of the developed tools is to allow studying the complex expression dependences that exist between sets of coexpressed genes. For this purpose, we start detecting the nonlinear expression relationships between pairs of genes, plus the coexpressed genes. Next, we form networks among sets of coexpressed genes that maintain nonlinear expression dependences between all of them. The expression relationship between the sets of coexpressed genes is defined by the expression relationship between the skeletons of these sets, where this skeleton represents the coexpressed genes with a well-defined nonlinear expression relationship with the skeleton of the other sets. As a result, we can study the nonlinear expression relationships between a target gene and other sets of coexpressed genes, or start the study from the skeleton of the sets, to study the complex relationships of activation and deactivation between the sets of coexpressed genes that carry out the different cellular processes present in the expression experiments.

Polymorphic variation in the androgen receptor gene: association with risk of testicular germ cell cancer and metastatic disease

DEFF Research Database (Denmark)

Västermark, Åke; Giwercman, Yvonne Lundberg; Hagströmer, Oskar

2011-01-01

Increasing incidence of testicular germ cell cancer (TGCC) is most probably related to environment and lifestyle. However, an underlying genetic predisposition may play a role and since sex steroids are assumed to be important for the rise and progression of TGCC, a study of androgen receptor (AR...... of endocrine disruptors. From a biological point of view, our findings strengthen the hypothesis of the importance of androgen action in the aetiology and pathogenesis of testicular malignancy. Future studies should focus on the impact of sex hormones on foetal germ cell development and the interaction between...

Gene expression of the mismatch repair gene MSH2 in primary colorectal cancer

DEFF Research Database (Denmark)

Jensen, Lars Henrik; Kuramochi, Hidekazu; Crüger, Dorthe Gylling

2011-01-01

promoter was only detected in 14 samples and only at a low level with no correlation to gene expression. MSH2 gene expression was not a prognostic factor for overall survival in univariate or multivariate analysis. The gene expression of MSH2 is a potential quantitative marker ready for further clinical...

Baldness and testicular cancer: the EPSAM case-control study.

Science.gov (United States)

Moirano, G; Zugna, D; Grasso, C; Lista, P; Ciuffreda, L; Segnan, N; Merletti, F; Richiardi, L

2016-03-01

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk. © 2016 American Society of Andrology and European Academy of Andrology.

The relationship among gene expression, the evolution of gene dosage, and the rate of protein evolution.

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Jean-François Gout

2010-05-01

Full Text Available The understanding of selective constraints affecting genes is a major issue in biology. It is well established that gene expression level is a major determinant of the rate of protein evolution, but the reasons for this relationship remain highly debated. Here we demonstrate that gene expression is also a major determinant of the evolution of gene dosage: the rate of gene losses after whole genome duplications in the Paramecium lineage is negatively correlated to the level of gene expression, and this relationship is not a byproduct of other factors known to affect the fate of gene duplicates. This indicates that changes in gene dosage are generally more deleterious for highly expressed genes. This rule also holds for other taxa: in yeast, we find a clear relationship between gene expression level and the fitness impact of reduction in gene dosage. To explain these observations, we propose a model based on the fact that the optimal expression level of a gene corresponds to a trade-off between the benefit and cost of its expression. This COSTEX model predicts that selective pressure against mutations changing gene expression level or affecting the encoded protein should on average be stronger in highly expressed genes and hence that both the frequency of gene loss and the rate of protein evolution should correlate negatively with gene expression. Thus, the COSTEX model provides a simple and common explanation for the general relationship observed between the level of gene expression and the different facets of gene evolution.

Noise minimization in eukaryotic gene expression.

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Hunter B Fraser

2004-06-01

Full Text Available All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or "noise." Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

Noise minimization in eukaryotic gene expression

Energy Technology Data Exchange (ETDEWEB)

Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

2004-01-15

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection.

Noise minimization in eukaryotic gene expression

International Nuclear Information System (INIS)

Fraser, Hunter B.; Hirsh, Aaron E.; Giaever, Guri; Kumm, Jochen; Eisen, Michael B.

2004-01-01

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or noise. Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection

Phthalate excretion pattern and testicular function

DEFF Research Database (Denmark)

Joensen, Ulla Nordström; Frederiksen, Hanne; Jensen, Martin Blomberg

2012-01-01

In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function.......In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function....

Positive selection on gene expression in the human brain

DEFF Research Database (Denmark)

Khaitovich, Philipp; Tang, Kun; Franz, Henriette

2006-01-01

Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

A stochastic approach to multi-gene expression dynamics

International Nuclear Information System (INIS)

Ochiai, T.; Nacher, J.C.; Akutsu, T.

2005-01-01

In the last years, tens of thousands gene expression profiles for cells of several organisms have been monitored. Gene expression is a complex transcriptional process where mRNA molecules are translated into proteins, which control most of the cell functions. In this process, the correlation among genes is crucial to determine the specific functions of genes. Here, we propose a novel multi-dimensional stochastic approach to deal with the gene correlation phenomena. Interestingly, our stochastic framework suggests that the study of the gene correlation requires only one theoretical assumption-Markov property-and the experimental transition probability, which characterizes the gene correlation system. Finally, a gene expression experiment is proposed for future applications of the model

Assays for noninvasive imaging of reporter gene expression

International Nuclear Information System (INIS)

Gambhir, S.S.; Barrio, J.R.; Herschman, H.R.; Phelps, M.E.

1999-01-01

Repeated, noninvasive imaging of reporter gene expression is emerging as a valuable tool for monitoring the expression of genes in animals and humans. Monitoring of organ/cell transplantation in living animals and humans, and the assessment of environmental, behavioral, and pharmacologic modulation of gene expression in transgenic animals should soon be possible. The earliest clinical application is likely to be monitoring human gene therapy in tumors transduced with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene. Several candidate assays for imaging reporter gene expression have been studied, utilizing cytosine deaminase (CD), HSV1-tk, and dopamine 2 receptor (D2R) as reporter genes. For the HSV1-tk reporter gene, both uracil nucleoside derivatives (e.g., 5-iodo-2'-fluoro-2'-deoxy-1-β-D-arabinofuranosyl-5-iodouracil [FIAU] labeled with 124 I, 131 I ) and acycloguanosine derivatives {e.g., 8-[ 18 F]fluoro-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (8-[ 18 F]-fluoroganciclovir) ([ 18 F]FGCV), 9-[(3-[ 18 F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG)} have been investigated as reporter probes. For the D2R reporter gene, a derivative of spiperone {3-(2'-[ 18 F]-Fluoroethyl)spiperone ([ 18 F]FESP)} has been used with positron emission tomography (PET) imaging. In this review, the principles and specific assays for imaging reporter gene expression are presented and discussed. Specific examples utilizing adenoviral-mediated delivery of a reporter gene as well as tumors expressing reporter genes are discussed

Microdissection of gonadal tissues for gene expression analyses

DEFF Research Database (Denmark)

Jørgensen, Anne; Dalgaard, Marlene Danner; Sonne, Si Brask

2011-01-01

Laser microdissection permits isolation of specific cell types from tissue sections or cell cultures. This may be beneficial when investigating the role of specific cells in a complex tissue or organ. In tissues with easily distinguishable morphology, a simple hematoxylin staining is sufficient...... phosphatase enzyme, such as fetal germ cells, testicular carcinoma in situ cells, and putatively also other early stem cell populations. We have applied these protocols for microdissection of rat Leydig cells, fetal human and zebrafish germ cells, and human testicular germ cell tumors, but the staining...

PRAME gene expression profile in medulloblastoma

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Tânia Maria Vulcani-Freitas

2011-02-01

Full Text Available Medulloblastoma is the most common malignant tumors of central nervous system in the childhood. The treatment is severe, harmful and, thus, has a dismal prognosis. As PRAME is present in various cancers, including meduloblastoma, and has limited expression in normal tissues, this antigen can be an ideal vaccine target for tumor immunotherapy. In order to find a potential molecular target, we investigated PRAME expression in medulloblastoma fragments and we compare the results with the clinical features of each patient. Analysis of gene expression was performed by real-time quantitative PCR from 37 tumor samples. The Mann-Whitney test was used to analysis the relationship between gene expression and clinical characteristics. Kaplan-Meier curves were used to evaluate survival. PRAME was overexpressed in 84% samples. But no statistical association was found between clinical features and PRAME overexpression. Despite that PRAME gene could be a strong candidate for immunotherapy since it is highly expressed in medulloblastomas.

Systematic identification of human housekeeping genes possibly useful as references in gene expression studies.

Science.gov (United States)

Caracausi, Maria; Piovesan, Allison; Antonaros, Francesca; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

2017-09-01

The ideal reference, or control, gene for the study of gene expression in a given organism should be expressed at a medium‑high level for easy detection, should be expressed at a constant/stable level throughout different cell types and within the same cell type undergoing different treatments, and should maintain these features through as many different tissues of the organism. From a biological point of view, these theoretical requirements of an ideal reference gene appear to be best suited to housekeeping (HK) genes. Recent advancements in the quality and completeness of human expression microarray data and in their statistical analysis may provide new clues toward the quantitative standardization of human gene expression studies in biology and medicine, both cross‑ and within‑tissue. The systematic approach used by the present study is based on the Transcriptome Mapper tool and exploits the automated reassignment of probes to corresponding genes, intra‑ and inter‑sample normalization, elaboration and representation of gene expression values in linear form within an indexed and searchable database with a graphical interface recording quantitative levels of expression, expression variability and cross‑tissue width of expression for more than 31,000 transcripts. The present study conducted a meta‑analysis of a pool of 646 expression profile data sets from 54 different human tissues and identified actin γ 1 as the HK gene that best fits the combination of all the traditional criteria to be used as a reference gene for general use; two ribosomal protein genes, RPS18 and RPS27, and one aquaporin gene, POM121 transmembrane nucleporin C, were also identified. The present study provided a list of tissue‑ and organ‑specific genes that may be most suited for the following individual tissues/organs: Adipose tissue, bone marrow, brain, heart, kidney, liver, lung, ovary, skeletal muscle and testis; and also provides in these cases a representative

Surviving testicular cancer: the Lebanese lived experience.

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Saab, Mohammad; Noureddine, Samar; Abu-Saad Huijer, Huda; Dejong, Jocelyn

2014-01-01

Testicular cancer is thought to have a great impact on its survivors, yet there has been limited literature on the topic globally and no literature on the topic in Lebanon and the Arab region. The purpose of this study was to explore the lived experience of Lebanese testicular cancer survivors and gain an in-depth understanding of the psychosexual aspect of their experience. A hermeneutic phenomenological approach with semistructured digitally recorded interviews and observational field notes was utilized. A purposive sample of Lebanese testicular cancer survivors, aged between 18 and 50 years, in remission for at least 3 years, and willing to share personal information was recruited. Interviews were transcribed verbatim in Arabic. Data saturation was achieved at the seventh interview; a total of eight informants were recruited. The opening question was, "Tell me about your life since you got treated for testicular cancer," and was followed by probing questions. Two to three weeks after the initial interview, informants were called to validate the investigators' primary analysis. Six core themes emerged: cancer perception in the Lebanese culture; "do not show, do not tell"; cancer experience is a turning point; fertility, manhood, and relationships; coping with cancer; and preserved aspects of life. The findings provide an in-depth understanding of the experience of Lebanese testicular cancer survivors with a focus on the psychosexual aspect of this experience. The results suggest the need to educate patients about testicular cancer and its effect on their fertility.

Green fluorescent protein as indicator of nonviral transient transfection efficiency in endometrial and testicular biopsies.

Science.gov (United States)

Zizzi, Antonio; Minardi, Daniele; Ciavattini, Andrea; Giantomassi, Federica; Montironi, Rodolfo; Muzzonigro, Giovanni; Di Primio, Roberto; Lucarini, Guendalina

2010-03-01

In the last years, physical and chemical methods of plasmid delivery have revolutionized the efficiency of nonviral gene transfer, and the success of gene therapy is largely dependent upon the development of gene-delivery methods. The nonviral techniques that lead to a direct transfer of DNA into tissue fragments, like electroporation (EP) and lipofection delivery systems are still insufficiently investigated. Our aim was to test the efficiency of EP and lipofection protocols in endometrial and testicular tissue fragments, using a naked plasmid DNA encoding green fluorescent protein (GFP). Because the transfection efficiency depends upon several factors, we tried to optimize the transfection conditions by testing different lipofectamine 2000 and plasmid ratios, electrical parameters, and culture after transfection. Our results show that these two nonviral methods of gene delivery are feasible and efficient in gene transfection of endometrial and testicular tissue biopsies. We found that the most performing ratio of plasmid:lipofectamine was 10:50 for transient lipofection, whereas two pulses for 10 s at 960 microF of capacitance, 200 V of voltage were the most favorable electrical parameters for EP efficiency in the presence of 5 microL of phMGFP plasmid. After lipofection and EP, the highest GFP intensity was observed respectively after 48 and 72 h of tissue fragment culturing. In conclusion, nonviral methods are attractive for an improvement of the gene therapy and our protocol could provide useful indications for in vivo gene therapy applications.

SIGNATURE: A workbench for gene expression signature analysis

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Chang Jeffrey T

2011-11-01

Full Text Available Abstract Background The biological phenotype of a cell, such as a characteristic visual image or behavior, reflects activities derived from the expression of collections of genes. As such, an ability to measure the expression of these genes provides an opportunity to develop more precise and varied sets of phenotypes. However, to use this approach requires computational methods that are difficult to implement and apply, and thus there is a critical need for intelligent software tools that can reduce the technical burden of the analysis. Tools for gene expression analyses are unusually difficult to implement in a user-friendly way because their application requires a combination of biological data curation, statistical computational methods, and database expertise. Results We have developed SIGNATURE, a web-based resource that simplifies gene expression signature analysis by providing software, data, and protocols to perform the analysis successfully. This resource uses Bayesian methods for processing gene expression data coupled with a curated database of gene expression signatures, all carried out within a GenePattern web interface for easy use and access. Conclusions SIGNATURE is available for public use at http://genepattern.genome.duke.edu/signature/.

Mining gene expression data of multiple sclerosis.

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Pi Guo

Full Text Available Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.Gene expression profiles based on the transcriptome of peripheral blood mononuclear cells from a total of 44 samples from 26 multiple sclerosis patients and 18 individuals with other neurological diseases (control were analyzed. Feature selection algorithms including Support Vector Machine based on Recursive Feature Elimination, Receiver Operating Characteristic Curve, and Boruta algorithms were jointly performed to select candidate genes associating with multiple sclerosis. Multiple classification models categorized samples into two different groups based on the identified genes. Models' performance was evaluated using cross-validation methods, and an optimal classifier for gene selection was determined.An overlapping feature set was identified consisting of 8 genes that were differentially expressed between the two phenotype groups. The genes were significantly associated with the pathways of apoptosis and cytokine-cytokine receptor interaction. TNFSF10 was significantly associated with multiple sclerosis. A Support Vector Machine model was established based on the featured genes and gave a practical accuracy of ∼86%. This binary classification model also outperformed the other models in terms of Sensitivity, Specificity and F1 score.The combined analytical framework integrating feature ranking algorithms and Support Vector Machine model could be used for selecting genes for other diseases.

Familial risks in testicular cancer as aetiological clues.

Science.gov (United States)

Hemminki, Kari; Chen, Bowang

2006-02-01

We used the nationwide Swedish Family-Cancer Database to analyse the risk for testicular cancer in offspring through parental and sibling probands. Among 0 to 70-year-old offspring, 4,586 patients had testicular cancer. Standardized incidence ratios for familial risk were 3.8-fold when a father and 7.6-fold when a brother had testicular cancer. Testicular cancer was associated with leukaemia, distal colon and kidney cancer, melanoma, connective tissue tumours and lung cancer in families. Non-seminoma was associated with maternal lung cancer but the risk was highest for the late-onset cases, providing no support to the theory of the in utero effect of maternal smoking on the son's risk of testicular cancer. However, the theory cannot be excluded but should be taken up for study when further data are available on maternal smoking. The high familial risk may be the product of shared childhood environment and heritable causes.

Plasticity-Related Gene Expression During Eszopiclone-Induced Sleep.

Science.gov (United States)

Gerashchenko, Dmitry; Pasumarthi, Ravi K; Kilduff, Thomas S

2017-07-01

Experimental evidence suggests that restorative processes depend on synaptic plasticity changes in the brain during sleep. We used the expression of plasticity-related genes to assess synaptic plasticity changes during drug-induced sleep. We first characterized sleep induced by eszopiclone in mice during baseline conditions and during the recovery from sleep deprivation. We then compared the expression of 18 genes and two miRNAs critically involved in synaptic plasticity in these mice. Gene expression was assessed in the cerebral cortex and hippocampus by the TaqMan reverse transcription polymerase chain reaction and correlated with sleep parameters. Eszopiclone reduced the latency to nonrapid eye movement (NREM) sleep and increased NREM sleep amounts. Eszopiclone had no effect on slow wave activity (SWA) during baseline conditions but reduced the SWA increase during recovery sleep (RS) after sleep deprivation. Gene expression analyses revealed three distinct patterns: (1) four genes had higher expression either in the cortex or hippocampus in the group of mice with increased amounts of wakefulness; (2) a large proportion of plasticity-related genes (7 out of 18 genes) had higher expression during RS in the cortex but not in the hippocampus; and (3) six genes and the two miRNAs showed no significant changes across conditions. Even at a relatively high dose (20 mg/kg), eszopiclone did not reduce the expression of plasticity-related genes during RS period in the cortex. These results indicate that gene expression associated with synaptic plasticity occurs in the cortex in the presence of a hypnotic medication. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Burned-Out Testicular Tumor: A Case Report

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N. Balalaa

2011-01-01

Full Text Available Germ cell tumors constitute the majority of all testicular tumors, which are relatively rare overall and are mainly encountered in young adults and teenagers. The term ‘burned-out’ germ cell tumor refers to the presence of a metastatic germ cell tumor with histological regression of the primary testicular lesion. Clinical examination of the testes and scrotal sonography is pivotal in the initial diagnosis of such neoplasms. We present a case of a 31-year-old male with a retroperitoneal mass and no palpable lesion on testicular examination.

Testicular lymphocytic vasculitis treated with prednisolone and azathioprine.

Science.gov (United States)

Kanzawa, Yohei; Imai, Yukihiro; Mizuno, Yasushi; Nishioka, Hiroaki

2017-07-01

Testicular vasculitis is a rare condition and little is known about its morphological features. Herein, we report a case of testicular lymphocytic vasculitis, which is rarely documented, in an elderly man. He presented with left testicular swelling and fever, but without any signs of other organ involvement. He was effectively treated with prednisolone and azathioprine. This case report offers information related to the disease course and the importance of biopsy.

Genetics Home Reference: 46,XX testicular disorder of sex development

Science.gov (United States)

... 46,XX testicular disorder of sex development 46,XX testicular disorder of sex development Printable PDF Open ... to view the expand/collapse boxes. Description 46,XX testicular disorder of sex development is a condition ...

Evaluation of suitable reference genes for gene expression studies in bovine muscular tissue

Directory of Open Access Journals (Sweden)

Dunner Susana

2008-09-01

Full Text Available Abstract Background Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RTqPCR is a technique used to measure mRNA species copy number as a way to determine key genes involved in different biological processes. However, the expression level of these key genes may vary among tissues or cells not only as a consequence of differential expression but also due to different factors, including choice of reference genes to normalize the expression levels of the target genes; thus the selection of reference genes is critical for expression studies. For this purpose, ten candidate reference genes were investigated in bovine muscular tissue. Results The value of stability of ten candidate reference genes included in three groups was estimated: the so called 'classical housekeeping' genes (18S, GAPDH and ACTB, a second set of genes used in expression studies conducted on other tissues (B2M, RPII, UBC and HMBS and a third set of novel genes (SF3A1, EEF1A2 and CASC3. Three different statistical algorithms were used to rank the genes by their stability measures as produced by geNorm, NormFinder and Bestkeeper. The three methods tend to agree on the most stably expressed genes and the least in muscular tissue. EEF1A2 and HMBS followed by SF3A1, ACTB, and CASC3 can be considered as stable reference genes, and B2M, RPII, UBC and GAPDH would not be appropriate. Although the rRNA-18S stability measure seems to be within the range of acceptance, its use is not recommended because its synthesis regulation is not representative of mRNA levels. Conclusion Based on geNorm algorithm, we propose the use of three genes SF3A1, EEF1A2 and HMBS as references for normalization of real-time RTqPCR in muscle expression studies.

Expression profiling identifies genes involved in emphysema severity

Directory of Open Access Journals (Sweden)

Bowman Rayleen V

2009-09-01

Full Text Available Abstract Chronic obstructive pulmonary disease (COPD is a major public health problem. The aim of this study was to identify genes involved in emphysema severity in COPD patients. Gene expression profiling was performed on total RNA extracted from non-tumor lung tissue from 30 smokers with emphysema. Class comparison analysis based on gas transfer measurement was performed to identify differentially expressed genes. Genes were then selected for technical validation by quantitative reverse transcriptase-PCR (qRT-PCR if also represented on microarray platforms used in previously published emphysema studies. Genes technically validated advanced to tests of biological replication by qRT-PCR using an independent test set of 62 lung samples. Class comparison identified 98 differentially expressed genes (p p Gene expression profiling of lung from emphysema patients identified seven candidate genes associated with emphysema severity including COL6A3, SERPINF1, ZNHIT6, NEDD4, CDKN2A, NRN1 and GSTM3.

Decoupling Linear and Nonlinear Associations of Gene Expression

KAUST Repository

Itakura, Alan

2013-05-01

The FANTOM consortium has generated a large gene expression dataset of different cell lines and tissue cultures using the single-molecule sequencing technology of HeliscopeCAGE. This provides a unique opportunity to investigate novel associations between gene expression over time and different cell types. Here, we create a MatLab wrapper for a powerful and computationally intensive set of statistics known as Maximal Information Coefficient, and then calculate this statistic for a large, comprehensive dataset containing gene expression of a variety of differentiating tissues. We then distinguish between linear and nonlinear associations, and then create gene association networks. Following this analysis, we are then able to identify clusters of linear gene associations that then associate nonlinearly with other clusters of linearity, providing insight to much more complex connections between gene expression patterns than previously anticipated.

Decoupling Linear and Nonlinear Associations of Gene Expression

KAUST Repository

Itakura, Alan

2013-01-01

The FANTOM consortium has generated a large gene expression dataset of different cell lines and tissue cultures using the single-molecule sequencing technology of HeliscopeCAGE. This provides a unique opportunity to investigate novel associations between gene expression over time and different cell types. Here, we create a MatLab wrapper for a powerful and computationally intensive set of statistics known as Maximal Information Coefficient, and then calculate this statistic for a large, comprehensive dataset containing gene expression of a variety of differentiating tissues. We then distinguish between linear and nonlinear associations, and then create gene association networks. Following this analysis, we are then able to identify clusters of linear gene associations that then associate nonlinearly with other clusters of linearity, providing insight to much more complex connections between gene expression patterns than previously anticipated.

Genetic architecture of gene expression in the chicken

Directory of Open Access Journals (Sweden)

Stanley Dragana

2013-01-01

Full Text Available Abstract Background The annotation of many genomes is limited, with a large proportion of identified genes lacking functional assignments. The construction of gene co-expression networks is a powerful approach that presents a way of integrating information from diverse gene expression datasets into a unified analysis which allows inferences to be drawn about the role of previously uncharacterised genes. Using this approach, we generated a condition-free gene co-expression network for the chicken using data from 1,043 publically available Affymetrix GeneChip Chicken Genome Arrays. This data was generated from a diverse range of experiments, including different tissues and experimental conditions. Our aim was to identify gene co-expression modules and generate a tool to facilitate exploration of the functional chicken genome. Results Fifteen modules, containing between 24 and 473 genes, were identified in the condition-free network. Most of the modules showed strong functional enrichment for particular Gene Ontology categories. However, a few showed no enrichment. Transcription factor binding site enrichment was also noted. Conclusions We have demonstrated that this chicken gene co-expression network is a useful tool in gene function prediction and the identification of putative novel transcription factors and binding sites. This work highlights the relevance of this methodology for functional prediction in poorly annotated genomes such as the chicken.

Early detection of testicular cancer: revisiting the role of self-efficacy in testicular self-examination among young asymptomatic males.

Science.gov (United States)

Umeh, Kanayo; Chadwick, Rebecca

2016-02-01

Research suggests that self-efficacy is an important factor in behaviors that facilitate the early-detection of various cancers. In general people with high self-efficacy are more likely to attend cancer screening sessions or perform bodily self-exams. However, there is a paucity of research focusing on testicular cancer and testicular self-examination (TSE). The effect of self-efficacy on TSE remains unclear especially given the relative obscurity of the testicular cancer threat, and appropriate clinical- and self-detection procedures, in the young asymptomatic male population. Thus, the present study tested the interaction of self-efficacy with young men's appraisals of the threat of testicular cancer. The study was based on 2 × 2 × 2 mixed factorial experimental design. Over 100 young asymptomatic men were exposed to a health warning about testicular cancer and randomly assigned to high/low self-efficacy, vulnerability, and severity conditions. High self-efficacy increased motivation to perform TSE given high vulnerability, but damaged attitudes to self-exams given low vulnerability and severity estimates. High self-efficacy also facilitated subsequent TSE. Overall, these findings support preexisting notions of self-efficacy but raise new questions about the moderating effects of threat appraisals.

Spermatogenesis and testicular tumours in ageing dogs

NARCIS (Netherlands)

Peters, M. A.; de rooij, D. G.; Teerds, K. J.; van der Gaag, I.; van Sluijs, F. J.

2000-01-01

Spermatogenesis was examined in testes from 74 dogs of various breeds without clinically detected testicular disease. A modified Johnsen score system was used to determine whether spermatogenesis deteriorates with ageing. The diameter of seminiferous tubules was measured in dogs without testicular

Bayesian assignment of gene ontology terms to gene expression experiments

Science.gov (United States)

Sykacek, P.

2012-01-01

Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

Bayesian assignment of gene ontology terms to gene expression experiments.

Science.gov (United States)

Sykacek, P

2012-09-15

Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

Gene expression profile data for mouse facial development

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Sonia M. Leach

2017-08-01

Full Text Available This article contains data related to the research articles "Spatial and Temporal Analysis of Gene Expression during Growth and Fusion of the Mouse Facial Prominences" (Feng et al., 2009 [1] and “Systems Biology of facial development: contributions of ectoderm and mesenchyme” (Hooper et al., 2017 In press [2]. Embryonic mammalian craniofacial development is a complex process involving the growth, morphogenesis, and fusion of distinct facial prominences into a functional whole. Aberrant gene regulation during this process can lead to severe craniofacial birth defects, including orofacial clefting. As a means to understand the genes involved in facial development, we had previously dissected the embryonic mouse face into distinct prominences: the mandibular, maxillary or nasal between E10.5 and E12.5. The prominences were then processed intact, or separated into ectoderm and mesenchyme layers, prior analysis of RNA expression using microarrays (Feng et al., 2009, Hooper et al., 2017 in press [1,2]. Here, individual gene expression profiles have been built from these datasets that illustrate the timing of gene expression in whole prominences or in the separated tissue layers. The data profiles are presented as an indexed and clickable list of the genes each linked to a graphical image of that gene׳s expression profile in the ectoderm, mesenchyme, or intact prominence. These data files will enable investigators to obtain a rapid assessment of the relative expression level of any gene on the array with respect to time, tissue, prominence, and expression trajectory.

Testicular Cancer Education in the Classroom.

Science.gov (United States)

Wohl, Royal E.

1998-01-01

Testicular cancer (TC) education is not widespread, though TC is the most common cancer in men ages 15-34 years. Teachers can positively influence young men by providing TC and testicular self-examination (TSE) education in school. The paper describes TC and TSE, discussing strategies for and barriers to implementation of TC/TSE instruction in the…

Integrated olfactory receptor and microarray gene expression databases

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Crasto Chiquito J

2007-06-01

Full Text Available Abstract Background Gene expression patterns of olfactory receptors (ORs are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB, which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction. Description ORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data. Conclusion ORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

Gene expression analysis of flax seed development

Science.gov (United States)

2011-01-01

Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise

Gene expression analysis of flax seed development

Directory of Open Access Journals (Sweden)

Sharpe Andrew

2011-04-01

Full Text Available Abstract Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages seed coats (globular and torpedo stages and endosperm (pooled globular to torpedo stages and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST (GenBank accessions LIBEST_026995 to LIBEST_027011 were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152 had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid

Testicular Metastasis of Prostate Cancer: A Case Report

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Ayumu Kusaka

2014-09-01

Full Text Available The incidence of secondary neoplasms of the testis during autopsies is approximately 2.5%. Although most secondary testicular metastases are due to prostate cancer, only a few patients with prostate cancer have clinically manifested testicular metastasis. We report the case of a prostate cancer patient with testicular metastasis who was diagnosed after the presence of a palpable mass in the right testis. A 56-year-old Japanese male presented to our hospital with an elevated serum prostate-specific antigen (PSA level of 137 ng/ml. He was diagnosed with stage IV (T3N1M1b prostate cancer and received androgen deprivation therapy, followed by various hormonal manipulations. His serum PSA level was undetectable for 1 year. No distant metastases were detected during imaging examinations. He received radiation therapy; however, his serum PSA level increased gradually. Four months later, he presented with right testicular swelling. Computed tomography revealed a heterogenous mass in the right testis and a right high inguinal orchiectomy was performed. Histopathological analysis showed that the right testis was infiltrated with metastatic adenocarcinoma with a Gleason score of 8. This is a rare case of right testicular metastasis in a patient with prostate cancer. Testicular metastasis of prostate cancer can be aggressive and metastasize.

Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

DEFF Research Database (Denmark)

Edsgärd, D; Scheel, M; Hansen, N T

2011-01-01

-associated genes among loci targeted by CNVs. The top-ranked candidate, RLN1, encoding a Relaxin-H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome-wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed....... Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population-wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible role...

Heterozygous deletion at the RLN1 locus in a family with testicular germ cell cancer identified by integrating copy number variation data with phenome and interactome information

DEFF Research Database (Denmark)

Edsgard, Stefan Daniel; Scheel, M.; Hansen, Niclas Tue

2011-01-01

‐associated genes among loci targeted by CNVs. The top‐ranked candidate, RLN1, encoding a Relaxin‐H1 peptide, although only detected in one of the families, was selected for further investigations. Validation of the CNV at the RLN1 locus was performed as an association study using qPCR with 106 sporadic testicular...... GCT patients and 200 healthy controls. Observed CNV frequencies of 1.9% among cases and 1.5% amongst controls were not significantly different and this was further confirmed by CNV data extracted from a genome‐wide analysis of 189 cases and 380 controls, where similar frequencies of 2.2% were observed...... and spermatids. Collectively, the findings show that a heterozygous loss at the RLN1 locus is not a genetic factor mediating high population‐wide risk for testicular germ cell tumour, but do not exclude a contribution of this aberration in some cases of cancer. The preliminary expression data suggest a possible...

Supplementary Material for: Global expression differences and tissue specific expression differences in rice evolution result in two contrasting types of differentially expressed genes

KAUST Repository

Horiuchi, Youko; Harushima, Yoshiaki; Fujisawa, Hironori; Mochizuki, Takako; Fujita, Masahiro; Ohyanagi, Hajime; Kurata, Nori

2015-01-01

Abstract Background Since the development of transcriptome analysis systems, many expression evolution studies characterized evolutionary forces acting on gene expression, without explicit discrimination between global expression differences and tissue specific expression differences. However, different types of gene expression alteration should have different effects on an organism, the evolutionary forces that act on them might be different, and different types of genes might show different types of differential expression between species. To confirm this, we studied differentially expressed (DE) genes among closely related groups that have extensive gene expression atlases, and clarified characteristics of different types of DE genes including the identification of regulating loci for differential expression using expression quantitative loci (eQTL) analysis data. Results We detected differentially expressed (DE) genes between rice subspecies in five homologous tissues that were verified using japonica and indica transcriptome atlases in public databases. Using the transcriptome atlases, we classified DE genes into two types, global DE genes and changed-tissues DE genes. Global type DE genes were not expressed in any tissues in the atlas of one subspecies, however changed-tissues type DE genes were expressed in both subspecies with different tissue specificity. For the five tissues in the two japonica-indica combinations, 4.6 ± 0.8 and 5.9 ± 1.5 % of highly expressed genes were global and changed-tissues DE genes, respectively. Changed-tissues DE genes varied in number between tissues, increasing linearly with the abundance of tissue specifically expressed genes in the tissue. Molecular evolution of global DE genes was rapid, unlike that of changed-tissues DE genes. Based on gene ontology, global and changed-tissues DE genes were different, having no common GO terms. Expression differences of most global DE genes were regulated by cis

K-RAS and N-RAS mutations in testicular germ cell tumors

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Bekir Muhammet Hacioglu

2017-05-01

Full Text Available Testicular cancer is a relatively rare tumor type, accounting for approximately 1% of all cancers in men. However, among men aged between 15 and 40 years, testicular cancer is the most commonly diagnosed malignancy. Testicular germ cell tumors (TGCTs are classified as seminoma and non-seminoma. The RAS oncogene controls several cellular functions, including cell proliferation, apoptosis, migration, and differentiation. Thus, RAS signaling is important for normal germ cell development. Mutations of the Kirsten RAS (K-RAS gene are present in over 20% of all cancers. RAS gene mutations have also been reported in TGCTs. We investigated K-RAS and N-RAS mutations in seminoma and non-seminoma TGCT patients. A total of 24 (55% pure seminoma cases and 19 (45% non-seminoma cases were included in the study. K-RAS and N-RAS analyses were performed in our molecular pathology laboratory, using K-RAS and N-RAS Pyro Kit 24 V1 (Qiagen. In total, a RAS mutation was present in 12 patients (27%: 7 seminoma (29% and 5 non-seminoma cases (26% [p = 0.55]. A K-RAS mutation was present in 4 pure seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63], and an N-RAS mutation was observed in 4 seminoma tumors (16% and 3 non-seminoma tumors (15% [p = 0.63]. Both, K-RAS and N-RAS mutations were present in two patients: one with seminoma tumor and the other with non-seminoma tumor. To date, no approved targeted therapy is available for the treatment of TGCTs. The analysis of K-RAS and N-RAS mutations in these tumors may provide more treatment options, especially in platinum-resistant tumors.

Identification of suitable reference genes for gene expression studies of shoulder instability.

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Mariana Ferreira Leal

Full Text Available Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially

Intermittent Testicular Torsion

African Journals Online (AJOL)

2017-12-05

, presence of abnormal testicular lie in otherwise normal testes, absence of urinary symptoms, and negative urine cultures. This diagnosis was confirmed by resolution of symptoms following bilateral orchidopexy. All patients ...

Surviving testicular cancer: : sexuality & other existential issues

NARCIS (Netherlands)

Pool, Grietje

2003-01-01

The thesis deals with the psychological aspects of ‘sexuality after testicular cancer’, where my collegue, the physician dr. Van Basten formerly predominantly described the physical-biological aspects of this subject. Testicular cancer is a type of male genital cancer, usually diagnosed between

Testicular lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; d'Amore, F; Christensen, Bjarne Egelund

1994-01-01

In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases...

Detecting microRNA activity from gene expression data

LENUS (Irish Health Repository)

Madden, Stephen F

2010-05-18

Abstract Background MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. Results Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. Conclusions We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

Detecting microRNA activity from gene expression data.

LENUS (Irish Health Repository)

Madden, Stephen F

2010-01-01

BACKGROUND: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression by binding to the messenger RNA (mRNA) of protein coding genes. They control gene expression by either inhibiting translation or inducing mRNA degradation. A number of computational techniques have been developed to identify the targets of miRNAs. In this study we used predicted miRNA-gene interactions to analyse mRNA gene expression microarray data to predict miRNAs associated with particular diseases or conditions. RESULTS: Here we combine correspondence analysis, between group analysis and co-inertia analysis (CIA) to determine which miRNAs are associated with differences in gene expression levels in microarray data sets. Using a database of miRNA target predictions from TargetScan, TargetScanS, PicTar4way PicTar5way, and miRanda and combining these data with gene expression levels from sets of microarrays, this method produces a ranked list of miRNAs associated with a specified split in samples. We applied this to three different microarray datasets, a papillary thyroid carcinoma dataset, an in-house dataset of lipopolysaccharide treated mouse macrophages, and a multi-tissue dataset. In each case we were able to identified miRNAs of biological importance. CONCLUSIONS: We describe a technique to integrate gene expression data and miRNA target predictions from multiple sources.

Gene expression results in lipopolysaccharide-stimulated monocytes depend significantly on the choice of reference genes

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Øvstebø Reidun

2010-05-01

Full Text Available Abstract Background Gene expression in lipopolysaccharide (LPS-stimulated monocytes is mainly studied by quantitative real-time reverse transcription PCR (RT-qPCR using GAPDH (glyceraldehyde 3-phosphate dehydrogenase or ACTB (beta-actin as reference gene for normalization. Expression of traditional reference genes has been shown to vary substantially under certain conditions leading to invalid results. To investigate whether traditional reference genes are stably expressed in LPS-stimulated monocytes or if RT-qPCR results are dependent on the choice of reference genes, we have assessed and evaluated gene expression stability of twelve candidate reference genes in this model system. Results Twelve candidate reference genes were quantified by RT-qPCR in LPS-stimulated, human monocytes and evaluated using the programs geNorm, Normfinder and BestKeeper. geNorm ranked PPIB (cyclophilin B, B2M (beta-2-microglobulin and PPIA (cyclophilin A as the best combination for gene expression normalization in LPS-stimulated monocytes. Normfinder suggested TBP (TATA-box binding protein and B2M as the best combination. Compared to these combinations, normalization using GAPDH alone resulted in significantly higher changes of TNF-α (tumor necrosis factor-alpha and IL10 (interleukin 10 expression. Moreover, a significant difference in TNF-α expression between monocytes stimulated with equimolar concentrations of LPS from N. meningitides and E. coli, respectively, was identified when using the suggested combinations of reference genes for normalization, but stayed unrecognized when employing a single reference gene, ACTB or GAPDH. Conclusions Gene expression levels in LPS-stimulated monocytes based on RT-qPCR results differ significantly when normalized to a single gene or a combination of stably expressed reference genes. Proper evaluation of reference gene stabiliy is therefore mandatory before reporting RT-qPCR results in LPS-stimulated monocytes.

Differentially expressed genes in iron-induced prion protein conversion

International Nuclear Information System (INIS)

Kim, Minsun; Kim, Eun-hee; Choi, Bo-Ran; Woo, Hee-Jong

2016-01-01

The conversion of the cellular prion protein (PrP C ) to the protease-resistant isoform is the key event in chronic neurodegenerative diseases, including transmissible spongiform encephalopathies (TSEs). Increased iron in prion-related disease has been observed due to the prion protein-ferritin complex. Additionally, the accumulation and conversion of recombinant PrP (rPrP) is specifically derived from Fe(III) but not Fe(II). Fe(III)-mediated PK-resistant PrP (PrP res ) conversion occurs within a complex cellular environment rather than via direct contact between rPrP and Fe(III). In this study, differentially expressed genes correlated with prion degeneration by Fe(III) were identified using Affymetrix microarrays. Following Fe(III) treatment, 97 genes were differentially expressed, including 85 upregulated genes and 12 downregulated genes (≥1.5-fold change in expression). However, Fe(II) treatment produced moderate alterations in gene expression without inducing dramatic alterations in gene expression profiles. Moreover, functional grouping of identified genes indicated that the differentially regulated genes were highly associated with cell growth, cell maintenance, and intra- and extracellular transport. These findings showed that Fe(III) may influence the expression of genes involved in PrP folding by redox mechanisms. The identification of genes with altered expression patterns in neural cells may provide insights into PrP conversion mechanisms during the development and progression of prion-related diseases. - Highlights: • Differential genes correlated with prion degeneration by Fe(III) were identified. • Genes were identified in cell proliferation and intra- and extracellular transport. • In PrP degeneration, redox related genes were suggested. • Cbr2, Rsad2, Slc40a1, Amph and Mvd were expressed significantly.

Regulation of meiotic gene expression in plants

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Adele eZhou

2014-08-01

Full Text Available With the recent advances in genomics and sequencing technologies, databases of transcriptomes representing many cellular processes have been built. Meiotic transcriptomes in plants have been studied in Arabidopsis thaliana, rice (Oryza sativa, wheat (Triticum aestivum, petunia (Petunia hybrida, sunflower (Helianthus annuus, and maize (Zea mays. Studies in all organisms, but particularly in plants, indicate that a very large number of genes are expressed during meiosis, though relatively few of them seem to be required for the completion of meiosis. In this review, we focus on gene expression at the RNA level and analyze the meiotic transcriptome datasets and explore expression patterns of known meiotic genes to elucidate how gene expression could be regulated during meiosis. We also discuss mechanisms, such as chromatin organization and non-coding RNAs, that might be involved in the regulation of meiotic transcription patterns.

Evaluating the consistency of gene sets used in the analysis of bacterial gene expression data

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Tintle Nathan L

2012-08-01

Full Text Available Abstract Background Statistical analyses of whole genome expression data require functional information about genes in order to yield meaningful biological conclusions. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG are common sources of functionally grouped gene sets. For bacteria, the SEED and MicrobesOnline provide alternative, complementary sources of gene sets. To date, no comprehensive evaluation of the data obtained from these resources has been performed. Results We define a series of gene set consistency metrics directly related to the most common classes of statistical analyses for gene expression data, and then perform a comprehensive analysis of 3581 Affymetrix® gene expression arrays across 17 diverse bacteria. We find that gene sets obtained from GO and KEGG demonstrate lower consistency than those obtained from the SEED and MicrobesOnline, regardless of gene set size. Conclusions Despite the widespread use of GO and KEGG gene sets in bacterial gene expression data analysis, the SEED and MicrobesOnline provide more consistent sets for a wide variety of statistical analyses. Increased use of the SEED and MicrobesOnline gene sets in the analysis of bacterial gene expression data may improve statistical power and utility of expression data.