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Sample records for assessing human germ-cell

  1. Elucidating human male germ cell development by studying germ cell cancer.

    Science.gov (United States)

    Nettersheim, Daniel; Jostes, Sina; Schneider, Simon; Schorle, Hubert

    2016-10-01

    Human germ cell development is regulated in a spatio-temporal manner by complex regulatory networks. Here, we summarize results obtained in germ cell tumors and respective cell lines and try to pinpoint similarities to normal germ cell development. This comparison allows speculating about the critical and error-prone mechanisms, which when disturbed, lead to the development of germ cell tumors. Short after specification, primordial germ cells express markers of pluripotency, which, in humans, persists up to the stage of fetal/infantile spermatogonia. Aside from the rare spermatocytic tumors, virtually all seminomas and embryonal carcinomas express markers of pluripotency and show signs of pluripotency or totipotency. Therefore, it appears that proper handling of the pluripotency program appears to be the most critical step in germ cell development in terms of tumor biology. Furthermore, data from mice reveal that germline cells display an epigenetic signature, which is highly similar to pluripotent cells. This signature (poised histone code, DNA hypomethylation) is required for the rapid induction of toti- and pluripotency upon fertilization. We propose that adult spermatogonial cells, when exposed to endocrine disruptors or epigenetic active substances, are prone to reinitiate the pluripotency program, giving rise to a germ cell tumor. The fact that pluripotent cells can be derived from adult murine and human testicular cells further corroborates this idea. PMID:27512122

  2. Meeting Report. Assessing Human Germ-Cell Mutagenesis in thePost-Genome Era: A Celebration of the Legacy of William Lawson (Bill)Russell

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, Andrew J.; Mulvihill, John J.; Wassom, John S.; Malling,Heinrich V.; Shelby, Michael D.; Lewis, Susan E.; Witt, Kristine L.; Preston, R. Julian; Perreault-Darney, Sally; Allen, James W.; DeMarini,David M.; Woychik, Richard P.; Bishop Jack B; Workshop Presenters

    2006-04-18

    Although numerous germ-cell mutagens have been identified inanimal model systems, to date, no human germ-cell mutagens have beenconfirmed. Because the genomic integrity of our germ cells is essentialfor the continuation of the human species, a resolution of this enduringconundrum is needed. To facilitate such a resolution, we organized aworkshop at The Jackson Laboratory in Bar Harbor, Maine on September28-30, 2004. This interactive workshop brought together scientists from awide range of disciplines to assess the applicability of emergingmolecular methods for genomic analysis to the field of human germ-cellmutagenesis. Participants recommended that focused, coordinated humangerm-cell mutation studies be conducted in relation to important societalexposures. Because cancer survivors represent a unique cohort withwell-defined exposures, there was a consensus that studies should bedesigned to assess the mutational impact on children born to parents whohad received certain types of mutagenic cancer chemotherapy prior toconceiving their children. Within this high-risk cohort, parents andchildren could be evaluated for inherited changes in (a) gene sequencesand chromosomal structure, (b) repeat sequences and minisatelliteregions, and (c) global gene expression and chromatin. Participants alsorecommended studies to examine trans-generational effects in humansinvolving mechanisms such as changes in imprinting and methylationpatterns, expansion of nucleotide repeats, or induction of mitochondrialDNA mutations. Workshop participants advocated establishment of abio-bank of human tissue samples that could be used to conduct amultiple-endpoint, comprehensive, and collaborative effort to detectexposure-induced heritable alterations in the human genome. Appropriateanimal models of human germ-cell mutagenes is should be used in parallelwith human studies to provide insights into the mechanisms of mammaliangerm-cell mutagenesis. Finally, participants recommended that

  3. Bone Morphogenetic Protein 4 Mediates Human Embryonic Germ Cell Derivation

    OpenAIRE

    Hiller, Marc; Liu, Cyndi; Blumenthal, Paul D; John D Gearhart; Kerr, Candace L.

    2010-01-01

    Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recom...

  4. Assessment of germ cell apoptosis in cryptorchid rats

    Institute of Scientific and Technical Information of China (English)

    IzzetKocak; MehmetDuendar

    2002-01-01

    Aim:To investigate the relationship between germ cell edgeneration and apoptosis in cryptorchid rats.Methods:Thirteen21-day-oldWistar rats were made unilaterally cryptorchid by closing the left inguinal canal.At day30(Group1,n =6)and day60(Group2,n=7)after operation,the testes were removed for histopathological examination.30(Group1,n=6)and day60(Group2,n=7)after operation,the testes were removed for histopathological examination.The controls(n=8)were sham operated and were sacrificed at day60.Germ cell apoptosis was assessed by means of theTUNEL method.Results:Spermatogenesis was arrested and the testicular and seminiferous tubular diameters were significantly reduced In the Unilateral undescended testes(UUTs)compared with the contralateral descended testes(CDTs)and the control rats.However,atrophic changes,pathological calcification,necrosis of seminiferous tubule,and absence or sloughing of germ cells were not found in all the animals,The spermatocytes were the main type of germ cells undergoing apoptosis in all the groups.In the UUTs,there was a significant and time-dependent increase in the mean apoptotic index.By60days after surgery,increased apoptosis in gern cells was also observed in the CDTs.Conclusion:Apoptosis is the predominant mechanism of germ cell death rather than atrophy and necrosis in cryptorchidism.

  5. Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

    DEFF Research Database (Denmark)

    Høyer, Poul Erik; Byskov, Anne Grete; Møllgård, Kjeld

    2005-01-01

    Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry......Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry...

  6. Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.

    Science.gov (United States)

    Dominguez, Antonia A; Chiang, H Rosaria; Sukhwani, Meena; Orwig, Kyle E; Reijo Pera, Renee A

    2014-09-22

    Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood.

  7. On the number of founding germ cells in humans

    Directory of Open Access Journals (Sweden)

    Byers Breck

    2005-08-01

    Full Text Available Abstract Background The number of founding germ cells (FGCs in mammals is of fundamental significance to the fidelity of gene transmission between generations, but estimates from various methods vary widely. In this paper we obtain a new estimate for the value in humans by using a mathematical model of germ cell development that depends on available oocyte counts for adult women. Results The germline-development model derives from the assumption that oogonial proliferation in the embryonic stage starts with a founding cells at t = 0 and that the subsequent proliferation can be defined as a simple stochastic birth process. It follows that the population size X(t at the end of germline expansion (around the 5th month of pregnancy in humans; t = 0.42 years is a random variable with a negative binomial distribution. A formula based on the expectation and variance of this random variable yields a moment-based estimate of a that is insensitive to the progressive reduction in oocyte numbers due to their utilization and apoptosis at later stages of life. In addition, we describe an algorithm for computing the maximum likelihood estimation of the FGC population size (a, as well as the rates of oogonial division and loss to apoptosis. Utilizing both of these approaches to evaluate available oocyte-counting data, we have obtained an estimate of a = 2 – 3 for Homo sapiens. Conclusion The estimated number of founding germ cells in humans corresponds well with values previously derived from chimerical or mosaic mouse data. These findings suggest that the large variation in oocyte numbers between individual women is consistent with a smaller founding germ cell population size than has been estimated by cytological analyses.

  8. Bone morphogenetic protein 4 mediates human embryonic germ cell derivation.

    Science.gov (United States)

    Hiller, Marc; Liu, Cyndi; Blumenthal, Paul D; Gearhart, John D; Kerr, Candace L

    2011-02-01

    Human primordial germ cells (PGCs) have proven to be a source of pluripotent stem cells called embryonic germ cells (EGCs). Unlike embryonic stem cells, virtually little is known regarding the factors that regulate EGC survival and maintenance. In mice, the growth factor bone morphogenetic protein 4 (BMP4) has been shown to be required for maintaining mouse embryonic stem cells, and disruptions in this gene lead to defects in mouse PGC specification. Here, we sought to determine whether recombinant human BMP4 could influence EGC derivation and/or human PGC survival. We found that the addition of recombinant BMP4 increased the number of human PGCs after 1 week of culture in a dose-responsive manner. The efficiency of EGC derivation and maintenance in culture was also enhanced by the presence of recombinant BMP4 based on alkaline phosphatase and OCT4 staining. In addition, an antagonist of the BMP4 pathway, Noggin, decreased PGC proliferation and led to an increase in cystic embryoid body formation. Quantitative real-time (qRT)-polymerase chain reaction analyses and immunostaining confirmed that the constituents of the BMP4 pathway were upregulated in EGCs versus PGCs. Downstream activators of the BMP4 pathway such as ID1 and phosphorylated SMADs 1 and 5 were also expressed, suggesting a role of this growth factor in EGC pluripotency. PMID:20486775

  9. Analysis of SOX2 expression in developing human testis and germ cell neoplasia

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Perrett, Rebecca M.; Nielsen, John Erik;

    2010-01-01

    The transcriptional regulators of pluripotency, POU5F1 (OCT4), NANOG and SOX2, are highly expressed in embryonal carcinoma (EC). In contrast to OCT4 and NANOG, SOX2 has not been demonstrated in the early human germ cell lineage or carcinoma in situ (CIS), the precursor for testicular germ cell tu...

  10. Molecular determinants of treatment response in human germ cell tumors

    NARCIS (Netherlands)

    F. Mayer; J.A. Stoop (Hans); G.L. Scheffer (George); R. Scheper; J.W. Oosterhuis (Wolter); L.H.J. Looijenga (Leendert); C. Bokemeyer

    2003-01-01

    textabstractPURPOSE: Germ cell tumors (GCTs) are highly sensitive to cisplatin-based chemotherapy. This feature is unexplained, as is the intrinsic chemotherapy resistance of mature teratomas and the resistant phenotype of a minority of refractory GCTs. Various cellular pathways ma

  11. MOLECULAR CHARACTERIZATION OF A RECURRING COMPLEX CHROMOSOMAL TRANSLOCATION IN 2 HUMAN EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    SINKE, RJ; WEGHUIS, DO; SUIJKERBUIJK, RF; TANIGAMI, A; NAKAMURA, Y; LARSSON, C; WEBER, G; DEJONG, B; OOSTERHUIS, JW; MOLENAAR, WM; VANKESSEL, AG

    1994-01-01

    The molecular characterization of a recurring complex chromosomal translocation involving 6p21, 6p22, 6p23, and 11q13 in two independent bur similar extragonadal human germ cell rumors was initiated using fluorescence in situ hybridization (FISH) and pulse field gel electrophoresis (PFGE) techniques

  12. Molecular characterization of a recurring complex chromosomal translocation in two human extragonadal germ cell tumors.

    NARCIS (Netherlands)

    Sinke, R J; Weghuis, D O; Suijkerbuijk, R F; Tanigami, A; Nakamura, Y; Larsson, C; Weber, G; Jong, B de; Oosterhuis, J W; Molenaar, W M

    1994-01-01

    The molecular characterization of a recurring complex chromosomal translocation involving 6p21, 6p22, 6q23, and 11q13 in two independent but similar extragonadal human germ cell tumors was initiated using fluorescence in situ hybridization (FISH) and pulse field gel electrophoresis (PFGE) techniques

  13. UNIPARENTAL ORIGIN OF I(12P) IN HUMAN GERM-CELL TUMORS

    NARCIS (Netherlands)

    SINKE, RJ; SUIJKERBUIJK, RF; DEJONG, B; OOSTERHUIS, JW; VANKESSEL, AG

    1993-01-01

    We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT-derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p-derived polymorphic markers. T

  14. Human papillomavirus and Epstein-Barr virus in the etiology of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Hørding, U; Nielsen, H W;

    1994-01-01

    sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace......Epidemiological features suggest that the risk of testicular cancer may be related to exposure to unknown infectious agents, including viruses. Therefore a series of twenty specimens of testicular germ cell tumours, including preinvasive carcinoma in-situ, were tested for the presence of DNA...... that a significant direct involvement of HPV and EBV in human testicular germ cell carcinogenesis is unlikely. However, a putative growth-stimulating role of EBV-transformed lymphocytes, which are frequently present in the stromal tissues of testicular tumours, cannot be excluded....

  15. Lipoprotein lipase and endothelial lipase in human testis and in germ cell neoplasms

    DEFF Research Database (Denmark)

    Nielsen, J E; Lindegaard, M L; Friis-Hansen, L;

    2009-01-01

    The aim of this study was to investigate endothelial lipase (EL, LIPG) and lipoprotein lipase (LPL) mRNA and protein expression in normal human testis and testicular germ cell tumours (GCT). Both EL and LPL were expressed in normal seminiferous tubules and in the interstitial compartment. EL m....... The results suggest that both EL and LPL participate in the supply of nutrients and steroidogenesis in the testes, and that especially EL may be important for the supply of cholesterol for testosterone production in the Leydig cells. The partial cellular separation of the expression of the two lipases...

  16. Assessment of the degree of contamination of rat germ cell preparations using specific cDNA probes

    Directory of Open Access Journals (Sweden)

    Savaris R.F.

    1997-01-01

    Full Text Available Recent reports showing a decrease in sperm count in men have brought new concerns about male infertility. Animal models have been widely used to provide some relevant information about the human male gamete, and extrapolations are made to men and to the clinical context. The present study assesses one of the methods used for separation of germ cells of the adult rat testis, namely centrifugal elutriation followed by density gradients (Percoll®. This method was chosen since it presents the best results for cell purity in separating germ cells from the rat testis. A comparison between continuous and discontinuous Percoll® gradients was performed in order to identify the best type of gradient to separate the cells. Maximal cell purity was obtained for spermatocytes (81 ± 8.2%, mean ± SEM and spermatids (84 ± 2.6% using centrifugal elutriation followed by continuous Percoll® gradients. A significant difference in purity was observed between elongating spermatids harvested from continuous Percoll® gradients and from discontinuous gradients. Molecular analysis was used to assess cell contamination by employing specific probes, namely transition protein 2 (TP2, mitochondrial cytochrome C oxidase II (COX II, and sulfated glycoprotein 1 (SGP1. Molecular analysis of the samples demonstrated that morphological criteria are efficient in characterizing the main composition of the cell suspension, but are not reliable for identifying minimal contamination from other cells. Reliable cell purity data should be established using molecular analysis

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

    DEFF Research Database (Denmark)

    Perrett, Rebecca M; Turnpenny, Lee; Eckert, Judith J;

    2008-01-01

    NANOG, POU5F1, and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which...... pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG, and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting, and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence...... of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected...

  19. Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J M; Beck, B L

    1995-01-01

    PURPOSE: We investigated the number of germ cells per tubular cross section and testicular weight in cryptorchid fetuses, neonates and infants, and characterized additional abnormalities. MATERIALS AND METHODS: Our series comprised 35 fetuses and 58 boys with cryptorchidism, and 22 normal fetuses...... number of germ cells in undescended testes from week 28 of gestation and germ cell hypoplasia as a consequence of continued postnatal undescended testicular position. Cryptorchidism may result from abnormal development of the caudal developmental field....

  20. Human primordial germ cell-derived progenitors give rise to neurons and glia in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Yincheng [Department of Gynecology and Obstetrics, The 6th People' s Hospital, School of Medicine, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233 (China); Chen, Bin [Center for Developmental Biology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kong Jiang Road, Shanghai 200092 (China); Tao, Minfang, E-mail: Taomf@126.com [Department of Gynecology and Obstetrics, The 6th People' s Hospital, School of Medicine, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233 (China)

    2009-12-18

    We derived a cell population from cultured human primordial germ cells from early human embryos. The derivates, termed embryoid body-derived (EBD) cells, displayed an extensive capacity for proliferation and expressed a panel of markers in all three germ layers. Interestingly, EBD cells were also positive for markers of neural stem/progenitor cells, such as nestin and glial fibrillary acidic protein. When these cells were transplanted into the brain cavities of fetal sheep and postnatal NOD-SCID mice or nerve-degenerated tibialis anterior muscles, they readily gave rise to neurons or glial cells. To our knowledge, our data are the first to demonstrate that EBD cells can undergo further neurogenesis under suitable environments in vivo. Hence, with the abilities of extensive expansion, self-renewal, and differentiation, EBD cells may provide a useful donor source for neural stem/progenitor cells to be used in cell-replacement therapies for diseases of the nervous system.

  1. CYTOGENETICS, PLOIDY AND DIFFERENTIATION OF HUMAN TESTICULAR, OVARIAN AND EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    OOSTERHUIS, JW; CASTEDO, SMMJ; DEJONG, B

    1990-01-01

    Data from cytogenetics of testicular, ovarian and extragonadal germ cell tumours indicate that the group of germ cell tumours for which Skakkebaek proposed the name gonocytoma (seminoma, dysgerminoma and germinoma) is characterized by the presence of isochromosome 12p. The (dysplastic) gonocytes fro

  2. 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

    -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...

  3. 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

    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...... 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...

  4. Germ cell numbers in human embryonic and fetal gonads during the first two trimesters of pregnancy: analysis of six published studies

    DEFF Research Database (Denmark)

    Mamsen, LS; Lutterodt, Melissa Catherine R; Andersen, Elisabeth Anne Wreford;

    2011-01-01

    The number of germ cells in human embryonic and fetal ovaries in relation to age is currently based on volumetric estimations from one study including a total of 12 ovaries. Six recent publications present stereological estimations of the number of germ cells in ovaries and testes for the first two...

  5. Production of human CD59-transgenic pigs by embryonic germ cell nuclear transfer

    International Nuclear Information System (INIS)

    Research highlights: → Human CD59 (hCD59) gene was introduced into porcine embryonic germ (EG) cells. → hCD59-transgenic EG cells were resistant to hyperacute rejection in cytolytic assay. → hCD59-transgenic pigs were produced by EG cell nuclear transfer. -- Abstract: This study was performed to produce transgenic pigs expressing the human complement regulatory protein CD59 (hCD59) using the nuclear transfer (NT) of embryonic germ (EG) cells, which are undifferentiated stem cells derived from primordial germ cells. Because EG cells can be cultured indefinitely in an undifferentiated state, they may provide an inexhaustible source of nuclear donor cells for NT to produce transgenic pigs. A total of 1980 NT embryos derived from hCD59-transgenic EG cells were transferred to ten recipients, resulting in the birth of fifteen piglets from three pregnancies. Among these offspring, ten were alive without overt health problems. Based on PCR analysis, all fifteen piglets were confirmed as hCD59 transgenic. The expression of the hCD59 transgene in the ten living piglets was verified by RT-PCR. Western analysis showed the expression of the hCD59 protein in four of the ten RT-PCR-positive piglets. These results demonstrate that hCD59-transgenic pigs could effectively be produced by EG cell NT and that such transgenic pigs may be used as organ donors in pig-to-human xenotransplantation.

  6. Production of human CD59-transgenic pigs by embryonic germ cell nuclear transfer

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Kwang Sung; Won, Ji Young [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of); Park, Jin-Ki [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Sorrell, Alice M. [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of); Heo, Soon Young; Kang, Jee Hyun [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of); Woo, Jae-Seok [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Choi, Bong-Hwan [Genomics and Bioinformatics Division, National Institute of Animal Science, Suwon (Korea, Republic of); Chang, Won-Kyong [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Shim, Hosup, E-mail: shim@dku.edu [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of); Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of)

    2010-10-01

    Research highlights: {yields} Human CD59 (hCD59) gene was introduced into porcine embryonic germ (EG) cells. {yields} hCD59-transgenic EG cells were resistant to hyperacute rejection in cytolytic assay. {yields} hCD59-transgenic pigs were produced by EG cell nuclear transfer. -- Abstract: This study was performed to produce transgenic pigs expressing the human complement regulatory protein CD59 (hCD59) using the nuclear transfer (NT) of embryonic germ (EG) cells, which are undifferentiated stem cells derived from primordial germ cells. Because EG cells can be cultured indefinitely in an undifferentiated state, they may provide an inexhaustible source of nuclear donor cells for NT to produce transgenic pigs. A total of 1980 NT embryos derived from hCD59-transgenic EG cells were transferred to ten recipients, resulting in the birth of fifteen piglets from three pregnancies. Among these offspring, ten were alive without overt health problems. Based on PCR analysis, all fifteen piglets were confirmed as hCD59 transgenic. The expression of the hCD59 transgene in the ten living piglets was verified by RT-PCR. Western analysis showed the expression of the hCD59 protein in four of the ten RT-PCR-positive piglets. These results demonstrate that hCD59-transgenic pigs could effectively be produced by EG cell NT and that such transgenic pigs may be used as organ donors in pig-to-human xenotransplantation.

  7. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    Directory of Open Access Journals (Sweden)

    Irma Virant-Klun

    2016-01-01

    Full Text Available MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human preimplantation development. They keep a balance between pluripotency and differentiation in the embryo and embryonic stem cells. Moreover, it became evident that dysregulation of microRNA expression may play a fundamental role in progression and dissemination of different cancers including ovarian cancer. The interest is still increased by the discovery of exosomes, that is, cell-derived vesicles, which can carry different proteins but also microRNAs between different cells and are involved in cell-to-cell communication. MicroRNAs, together with exosomes, have a great potential to be used for prognosis, therapy, and biomarkers of different diseases including infertility. The aim of this review paper is to summarize the existent knowledge on microRNAs related to female fertility and cancer: from primordial germ cells and ovarian function, germinal stem cells, oocytes, and embryos to embryonic stem cells.

  8. Deregulation of the RB pathway in human testicular germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, Jirina; Lukas, Claudia; Sørensen, Claus S;

    2003-01-01

    Deregulation of the RB pathway is shared by most human malignancies. Components upstream of the retinoblastoma tumour suppressor (pRB), namely the INK4 family of cyclin-dependent kinase (CDK) inhibitors, the D-type cyclins, their partner kinases CDK4/CDK6, and pRB as their critical substrate......, are differentially targeted in diverse types of cancer. An 'unorthodox' spectrum of defects within this cascade occurs in testicular germ cell tumours (TGCTs), including silencing of pRB transcription, overexpression of cyclin D2, and loss of p18INK4c. To improve understanding of the role of this pathway...... in spermatogenesis, and its subversion in TGCTs, we examined immunohistochemical expression patterns of CDK4, p16INK4a, p15INK4b, and pRB, and established an in situ assay for cyclin D-mediated phosphorylation of serine795, a phosphorylation event critical for neutralization of pRB's growth-restraining ability. pRB...

  9. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

    DEFF Research Database (Denmark)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B;

    2013-01-01

    development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

  10. Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

    DEFF Research Database (Denmark)

    Bartkova, J; Moudry, P; Hodny, Z;

    2011-01-01

    of germ cells vs. somatic tissues in early tumourigenesis. Conceptually interesting findings were that subsets of human cells in vivo proliferate despite enhanced heterochromatinization, and that cells can strongly express even multiple heterochromatin features in the absence of functional retinoblastoma...

  11. Quantitative histology of germ cells in the undescended testes of human fetuses, neonates and infants

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J M; Beck, B L

    1995-01-01

    PURPOSE: We investigated the number of germ cells per tubular cross section and testicular weight in cryptorchid fetuses, neonates and infants, and characterized additional abnormalities. MATERIALS AND METHODS: Our series comprised 35 fetuses and 58 boys with cryptorchidism, and 22 normal fetuses...

  12. Recommended Ethical Safeguards on Fertilization of Human Germ Cells Derived from Pluripotent Stem Cells Solely for Research Purposes.

    Science.gov (United States)

    Mizuno, Hiroshi

    2016-08-01

    Production of human fertilized embryos by using germ cells derived from pluripotent stem cells (PSCs) entails ethical issues that differ fundamentally depending on the aim. If the aim is solely to conduct research, then embryo generation, utilization and destruction must respect for the human embryo as having the innate potential to develop into a human being. If the aim is human reproduction, this technology must never be used to manipulate human life, confuse social order, or negatively affect future generations. Researchers should distinguish the aims and then accordingly establish a consensus on the safeguards needed to proceed with scientifically significant and socially accepted research, or otherwise set a moratorium. Currently, in Japan, germ cell production from human PSCs is permitted, whereas fertilization of these germ cells is not. The Japanese Expert Panel on Bioethics in the Cabinet Office has proposed that all of the following conditions must be met to approve fertilization for research purposes: (1) the research is significant for the life sciences and medicine; (2) the benefits or anticipated benefits are socially accepted; (3) human safety is assured; and (4) safeguards are put in place. If fertilization is ethically approved, I recommend the following safeguards: limitation of the purpose to improving conventional ART as an initial step; permitted culture of human embryos until the appearance of the primitive streak; restriction of the number of embryos produced to the minimum necessary; prohibition of transplantation into a human or animal uterus; and provision of human-derived ova that are not required for ART treatment. PMID:27276914

  13. DNA damage in human germ cell exposed to the some food additives in vitro.

    Science.gov (United States)

    Pandir, Dilek

    2016-08-01

    The use of food additives has increased enormously in modern food technology but they have adverse effects in human healthy. The aim of this study was to investigate the DNA damage of some food additives such as citric acid (CA), benzoic acid (BA), brilliant blue (BB) and sunset yellow (SY) which were investigated in human male germ cells using comet assay. The sperm cells were incubated with different concentrations of these food additives (50, 100, 200 and 500 μg/mL) for 1 h at 32 °C. The results showed for CA, BA, BB and SY a dose dependent increase in tail DNA%, tail length and tail moment in human sperm when compared to control group. When control values were compared in the studied parameters in the treatment concentrations, SY was found to exhibit the highest level of DNA damage followed by BB > BA > CA. However, none of the food additives affected the tail DNA%, tail length and tail moment at 50 and 100 μg/mL. At 200 μg/mL of SY, the tail DNA% and tail length of sperm were 95.80 ± 0.28 and 42.56 ± 4.66, for BB the values were 95.06 ± 2.30 and 39.56 ± 3.78, whereas for BA the values were 89.05 ± 2.78 and 31.50 ± 0.71, for CA the values were 88.59 ± 6.45 and 13.59 ± 2.74, respectively. However, only the highest concentration of the used food additives significantly affected the studied parameters of sperm DNA. The present results indicate that SY and BB are more harmful than BA and CA to human sperm in vitro. PMID:25501537

  14. Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice.

    Science.gov (United States)

    Wang, Shu Pei; Chung, Shari; Soni, Krishnakant; Bourdages, Hugo; Hermo, Louis; Trasler, Jacquetta; Mitchell, Grant A

    2004-12-01

    Hormone-sensitive lipase (HSL, Lipe, E.C.3.1.1.3) is a multifunctional fatty acyl esterase that is essential for male fertility and spermatogenesis and that also plays important roles in the function of adipocytes, pancreatic beta-cells, and adrenal cortical cells. Gene-targeted HSL-deficient (HSL-/-) male mice are infertile, have a 2-fold reduction in testicular mass, a 2-fold elevation of the ratio of esterified to free cholesterol in testis, and unique morphological abnormalities in round and elongating spermatids. Postmeiotic germ cells in the testis express a specific HSL isoform. We created transgenic mice expressing a normal human testicular HSL cDNA from the mouse protamine-1 promoter, which mediates expression specifically in postmeiotic germ cells. Testicular cholesteryl esterase activity was undetectable in HSL-/- mice, but in HSL-/- males expressing the testicular transgene, activity was 2-fold greater than normal. HSL transgene mRNA became detectable in testes between 19 and 25 days of age, coinciding with the first wave of postmeiotic transcription in round spermatids. In contrast to nontransgenic HSL-/- mice, HSL-/- males expressing the testicular transgene were normal with respect to fertility, testicular mass, testicular esterified/free cholesterol ratio, and testicular histology. Their cauda epididymides contained abundant, normal-appearing spermatozoa. We conclude that human testicular HSL is functional in mouse testis and that the mechanism of infertility in HSL-deficient males is cell autonomous and resides in postmeiotic germ cells, because HSL expression in these cells is in itself sufficient to restore normal fertility.

  15. Regulation of Translocator Protein 18 kDa (TSPO Expression in Rat and Human Male Germ Cells

    Directory of Open Access Journals (Sweden)

    Gurpreet Manku

    2016-09-01

    Full Text Available Translocator protein 18 kDa (TSPO is a high affinity cholesterol- and drug-binding protein highly expressed in steroidogenic cells, such as Leydig cells, where it plays a role in cholesterol mitochondrial transport. We have previously shown that TSPO is expressed in postnatal day 3 rat gonocytes, precursors of spermatogonial stem cells. Gonocytes undergo regulated phases of proliferation and migration, followed by retinoic acid (RA-induced differentiation. Understanding these processes is important since their disruption may lead to the formation of carcinoma in situ, a precursor of testicular germ cell tumors (TGCTs. Previously, we showed that TSPO ligands do not regulate gonocyte proliferation. In the present study, we found that TSPO expression is downregulated in differentiating gonocytes. Similarly, in F9 embryonal carcinoma cells, a mouse TGCT cell line with embryonic stem cell properties, there is a significant decrease in TSPO expression during RA-induced differentiation. Silencing TSPO expression in gonocytes increased the stimulatory effect of RA on the expression of the differentiation marker Stra8, suggesting that TSPO exerts a repressive role on differentiation. Furthermore, in normal human testes, TSPO was located not only in Leydig cells, but also in discrete spermatogenic phases such as the forming acrosome of round spermatids. By contrast, seminomas, the most common type of TGCT, presented high levels of TSPO mRNA. TSPO protein was expressed in the cytoplasmic compartment of seminoma cells, identified by their nuclear expression of the transcription factors OCT4 and AP2G. Thus, TSPO appears to be tightly regulated during germ cell differentiation, and to be deregulated in seminomas, suggesting a role in germ cell development and pathology.

  16. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders;

    2015-01-01

    reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially...... in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which...... are essentially the same precursor lesion but with different morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published...

  17. [Incidence and Risk Assessment of Tumor Lysis Syndrome in Patients with Advanced Germ Cell Cancer].

    Science.gov (United States)

    Kurobe, Masahiro; Kawai, Koji; Tanaka, Ken; Ichioka, Daishi; Yoshino, Takayuki; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Takaoka, Ei-Ichirou; Kojima, Takahiro; Joraku, Akira; Suetomi, Takahiro; Miyazaki, Jun; Nishiyama, Hiroyuki

    2016-05-01

    Tumor lysis syndrome (TLS) is a major oncological emergency. TLS is common in patients with hematological malignancies, but it can occur across a spectrum of cancer types. Germ cell tumors (GCT) have rapid cancer cell turnover and often present with bulky metastasis. The international TLS expert consensus panel has recommended guidelines for a medical decision tree to assign low, intermediate and high risk to patients with cancer at risk for TLS. GCT is classified as intermediate risk for TLS, and the patients who have other TLS risks factors are classified to be at high risk for TLS. In this study, we retrospectively analyzed 67 patients with metastatic GCT who were treated with induction chemotherapy at Tsukuba University Hospital between 2000 and 2013. Thirty-one, 15 and 21 patients were classified with good-, intermediate- and poor-prognosis disease, respectively, according to the International Germ Cell Cancer Collaborative Group criteria. Twelve patients (18%) were classified to be at high risk for TLS, and two patients were treated with allopurinol or rasburicase as prophylaxes for TLS. They did not show progression to laboratory TLS (L-TLS). In the remaining 10 TLS high-risk patients, three (30%) patients developed L-TLS after chemotherapy and started receiving oral allopurinol. As a result, no patients developed clinical TLS (C-TLS). In this study, 30% of TLS-high risk patients developed L-TLS without prophylactic treatment. Therefore, it is important to conduct TLS-risk stratification and consider prophylaxis such as rasburicase for advanced GCT patients at induction chemotherapy. PMID:27320114

  18. Granulosa cells and retinoic acid co-treatment enrich potential germ cells from manually selected Oct4-EGFP expressing human embryonic stem cells.

    Science.gov (United States)

    Chen, Hsin-Fu; Jan, Pey-Shynan; Kuo, Hung-Chih; Wu, Fang-Chun; Lan, Chen-Wei; Huang, Mei-Chi; Chien, Chung-Liang; Ho, Hong-Nerng

    2014-09-01

    Differentiation of human embryonic stem (HES) cells to germ cells may become clinically useful in overcoming diseases related to germ-cell development. Niches were used to differentiate HES cell lines, NTU1 and H9 Oct4-enhanced green fluorescence protein (EGFP), including laminin, granulosa cell co-culture or conditioned medium, ovarian stromal cell co-culture or conditioned medium, retinoic acid, stem cell factor (SCF) and BMP4-BMP7-BMP8b treatment. Flow cytometry showed that granulosa cell co-culture (P cells expressing early germ cell marker stage-specific embryonic antigen 1(SSEA1); sorted SSEA1[+] cells did not express higher levels of germ cell gene VASA and GDF9. Manually collected H9 Oct4-EGFP[+] cells expressed significantly higher levels of VASA (P = 0.005) and GDF9 (P = 0.001). H9 Oct4-EGFP[+] cells developed to ovarian follicle-like structures after culture for 28 days but with low efficiency. Unlike SCF and BMP4, retinoic acid co-treatment enhanced VASA, GDF9 and SCP3 expression. A protocol is recommended to enrich differentiated HES cells with germ-cell potential by culture with granulosa cells, conditioned medium or retinoic acid, manual selection of Oct4-EGFP[+] cells, and analysis of VASA, GDF9 expression, or both.

  19. Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis

    Directory of Open Access Journals (Sweden)

    Coutts Shona

    2007-12-01

    Full Text Available Abstract Background Germ cells arise from a small group of cells that express markers of pluripotency including OCT4. In humans formation of gonadal compartments (cords in testis, nests in ovary takes place during the 1st trimester (6–8 weeks gestation. In the 2nd trimester germ cells can enter meiotic prophase in females whereas in males this does not occur until puberty. We have used qRTPCR, Westerns and immunohistochemical profiling to determine which of the germ cell subtypes in the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to play an essential role in germ cell maturation in mice. Results OCT4 mRNA and protein were detected in extracts from both 1st and 2nd trimester ovaries and testes. In ovarian extracts a marked increase in expression of VASA and DAZL mRNA and protein occurred in the 2nd trimester. In testicular extracts VASA mRNA and protein were low/undetectable in 1st trimester and increased in the 2nd trimester whereas the total amount of DAZL did not seem to change. During the 1st trimester, germ cells were OCT4 positive but did not express VASA. These results are in contrast to the situation in mice where expression of Vasa is initiated in Oct4 positive primordial germ cells as they enter the gonadal ridge. In the 2nd trimester germ cells with intense cytoplasmic staining for VASA were present in both sexes; these cells were OCT4 negative. DAZL expression overlapped with both OCT4 and VASA and changed from the nuclear to the cytoplasmic compartment as cells became OCT4-negative. In males, OCT4-positive and VASA-positive subpopulations of germ cells coexisted within the same seminiferous cords but in the ovary there was a distinct spatial distribution of cells with OCT4 expressed by smaller, peripherally located, germ cells whereas DAZL and VASA were immunolocalised to larger (more mature centrally located cells. Conclusion OCT4, DAZL and VASA are expressed by human fetal germ cells but their

  20. Overexpression of karyopherin 2 in human ovarian malignant germ cell tumor correlates with poor prognosis.

    Directory of Open Access Journals (Sweden)

    Li He

    Full Text Available BACKGROUND: The aim of this study was to identify a biomarker useful in the diagnosis and therapy of ovarian malignant germ cell tumor (OMGCT. METHODS: The karyopherin 2 (KPNA2 expression in OMGCT and normal ovarian tissue was determined by standard gene microarray assays, and further validated by a quantitative RT-PCR and immunohistochemistry. The correlation between KPNA2 expression in OMGCT and certain clinicopathological features were analyzed. Expression of SALL4, a stem cell marker, was also examined in comparison with KPNA2. RESULTS: KPNA2 was found to be over-expressed by approximately eight-fold in yolk sac tumors and immature teratomas compared to normal ovarian tissue by microarray assays. Overexpression was detected in yolk sac tumors, immature teratomas, dysgerminomas, embryonal carcinomas, mature teratomas with malignant transformation and mixed ovarian germ cell tumors at both the transcription and translation levels. A positive correlation between KPNA2 and SALL4 expression at both the transcription level (R = 0.5120, P = 0.0125, and the translation level (R = 0.6636, P<0.0001, was presented. Extensive expression of KPNA2 was positively associated with pathologic type, recurrence and uncontrolled, ascitic fluid presence, suboptimal cytoreductive surgery necessity, resistance/refraction to initial chemotherapy, HCG level and SALL4 level in OMGCT patients. KPNA2 was found to be an independent factor for 5-year disease-free survival (DFS of OMGCT (P = 0.02. The 5-year overall survival (OS and DFS rate for KPNA2-low expression patients (88% and 79%, n = 48 were significantly higher than the OS and DFS rate for KPNA2-high expression patients (69% and 57.1%, n = 42(P = 0.0151, P = 0.0109, respectively. The 5-year OS and DFS rate for SALL4-low expression patients (84% and 74%, n = 62 was marginally significantly higher than the high expression patients (78.6% and 71.4%, n = 28(P = 0.0519, P = 0.0647, respectively. CONCLUSIONS: KPNA2 is

  1. Proliferation of germ cells and somatic cells in first trimester human embryonic gonads as indicated by S and S+G2+M phase fractions

    DEFF Research Database (Denmark)

    Sørensen, K P; Lutterodt, M C; Mamsen, L S;

    2011-01-01

    The number of germ cells and somatic cells in human embryonic and foetal gonads has previously been estimated by stereological methods, which are time- and labour-consuming with little information concerning cell proliferation. Here, we studied whether flow cytometry could be applied as an easier...

  2. Familial germ cell tumor

    Directory of Open Access Journals (Sweden)

    Sanju Cyriac

    2012-01-01

    Full Text Available Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile.

  3. Familial germ cell tumor

    OpenAIRE

    Sanju Cyriac; Rejeev Rajendranath; A. Robert Louis; Sagar, T. G.

    2012-01-01

    Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presenc...

  4. Intracranial germ cell tumor

    OpenAIRE

    Kreutz, J; Rausin, L.; Weerts, E; Tebache, M; Born, J; Hoyoux, C

    2010-01-01

    Germ cell tumours represent about 3 to 8% of pediatric brain tumours. Occurrence of diabetes insipidus is common in the case of suprasellar germ cell tumors. The diagnosis may be advanced by MRI owing to the location and relatively univocal characteristics of the lesion signal. The existence of a bifocal mass developed in both suprasellar region and pineal zone is highly suggestive of a germinoma. The most important notion is to recognize that at the time of diabetes insipidus diagnosis in a ...

  5. Quantification of human telomerase reverse transcriptase mRNA in testicular germ cell tumors by quantitative fluorescence real-time RT-PCR.

    Science.gov (United States)

    Schrader, Mark; Burger, Angelika M; Müller, Markus; Krause, Hans; Straub, Bernd; Smith, Gilian L; Newlands, Eward S; Miller, Kurt

    2002-01-01

    Telomerase is a ribonucleoprotein enzyme which is endogenously expressed in germ, stem and tumor cells, but absent in benign somatic cells. The two major telomerase components are human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT). It has been shown that hTERT is rate-limiting for telomerase activity and that it plays a central role in human carcinogenesis. Here, we investigated the potential of hTERT and hTR gene expression as diagnostic markers in testicular germ cell tumors (TGCT). hTERT mRNA and hTR expression were quantified in 55 testicular germ cell tumors comprising 36 primary and 19 germ cell tumors from retroperitonal sides by fluorescence real-time RT-PCR using the LightCycler technology. Porphobilinogen deaminase (PBGD) was used as housekeeping gene and to enable relative quantification. For comparison to TGCTs, 38 benign testicular biopsies from patients with fertility disorders were assayed. hTERT expression was detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content (N(hTERT) 38-127). In contrast, mature teratomas from primary and post-chemotherapy masses, which are characterized by well-differentiated tissue components showed a nearly complete downregulation of hTERT expression (N(hTERT) 2-4, pmRNA is expressed in all undifferentiated TGCTs but repressed in mature teratomas. This suggests an inverse correlation between the differentiation status of germ cell tumors and hTERT expression. Thus, detection of hTERT expression in tumors histopathologically classified as mature teratomas enables a molecular-diagnostic confirmation and might aid decision making for treatment of patients presenting with this tumor subtype.

  6. HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines

    Science.gov (United States)

    Yunusov, Dinar; Anderson, Leticia; Dasilva, Lucas Ferreira; Wysocka, Joanna; Ezashi, Toshihiko; Roberts, R. Michael; Verjovski-Almeida, Sergio

    2016-09-01

    Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR has evolutionarily conserved expression patterns, its promoter is most active in undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP cells predominantly affects the genes involved in early organismal development and cell differentiation. Most importantly, we find that HIPSTR is specifically induced and heterogeneously expressed in the 8-cell-stage human embryos during the major wave of embryonic genome activation. We systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, the expression of thousands of lncRNAs is more highly heterogeneous than the expression of mRNAs in the individual, otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines.

  7. HIPSTR and thousands of lncRNAs are heterogeneously expressed in human embryos, primordial germ cells and stable cell lines

    Science.gov (United States)

    Yunusov, Dinar; Anderson, Leticia; DaSilva, Lucas Ferreira; Wysocka, Joanna; Ezashi, Toshihiko; Roberts, R. Michael; Verjovski-Almeida, Sergio

    2016-01-01

    Eukaryotic genomes are transcribed into numerous regulatory long non-coding RNAs (lncRNAs). Compared to mRNAs, lncRNAs display higher developmental stage-, tissue-, and cell-subtype-specificity of expression, and are generally less abundant in a population of cells. Despite the progress in single-cell-focused research, the origins of low population-level expression of lncRNAs in homogeneous populations of cells are poorly understood. Here, we identify HIPSTR (Heterogeneously expressed from the Intronic Plus Strand of the TFAP2A-locus RNA), a novel lncRNA gene in the developmentally regulated TFAP2A locus. HIPSTR has evolutionarily conserved expression patterns, its promoter is most active in undifferentiated cells, and depletion of HIPSTR in HEK293 and in pluripotent H1BP cells predominantly affects the genes involved in early organismal development and cell differentiation. Most importantly, we find that HIPSTR is specifically induced and heterogeneously expressed in the 8-cell-stage human embryos during the major wave of embryonic genome activation. We systematically explore the phenomenon of cell-to-cell variation of gene expression and link it to low population-level expression of lncRNAs, showing that, similar to HIPSTR, the expression of thousands of lncRNAs is more highly heterogeneous than the expression of mRNAs in the individual, otherwise indistinguishable cells of totipotent human embryos, primordial germ cells, and stable cell lines. PMID:27605307

  8. Extragonadal Germ Cell Cancer (EGC)

    Science.gov (United States)

    ... Testicular Cancer Resource Center Extragonadal Germ Cell Cancer (EGC) 95% of all testicular tumors are germ cell ... seen in young adults. Patients with mediastinal nonseminomatous EGC are typically classed as poor risk patients because ...

  9. Mouse autosomal homolog of DAZ, a candidate male sterility gene in humans, is expressed in male germ cells before and after puberty

    Energy Technology Data Exchange (ETDEWEB)

    Reijo, R.; Seligman, J.; Jaffe, T. [Massachusetts Institute of Technology, Cambridge, MA (United States)] [and others

    1996-07-15

    Deletion of the Azoospermia Factor (AZF) region of the human Y chromosome results in spermatogenic failure. While the identity of the critical missing gene has yet to be established, a strong candidate is the putative RNA-binding protein DAZ (Deleted in Azoospermia). Here we describe the mouse homolog of DAZ. Unlike human DAZ, which is Y-linked, in mouse the Dazh (DAZ homolog) gene maps to chromosome 17. Nonetheless, the predicted amino acid sequences of the gene products are quite similar, especially in their RNP/RRM (putative RNA-binding) domains, and both genes are transcribed predominantly in testes; the mouse gene is transcribed at a lower level in ovaries. Dazh transcripts were not detected in testes of mice that lack germ cells. In testes of wildtype mice, Dazh transcription is detectable 1 day after birth (when the only germ cells are prospermatogonia), increases steadily as spermatogonial stem cells appear, plateaus as the first wave of spermatogenic cells enters meiosis (10 days after birth), and is sustained at this level thereafter. This unique pattern of expression suggests the Dazh participates in differentiation, proliferation, or maintenance of germ cell founder populations before, during, and after the pubertal onset of spermatogenesis. Such functions could readily account for the diverse spermatogenic defects observed in human males with AZF deletion. 29 refs., 4 figs.

  10. MONOCLONAL-ANTIBODIES TO HUMAN EMBRYONAL CARCINOMA-CELLS - ANTIGENIC RELATIONSHIPS OF GERM-CELL TUMORS

    NARCIS (Netherlands)

    DEWIT, TFR; WILSON, L; VANDENELSEN, PJ; THIELEN, F; BREKHOFF, D; OOSTERHUIS, JW; PERA, MF; STERN, PL

    1991-01-01

    Fifteen monoclonal antibodies (mAb) that show specificity for human embryonal carcinoma cells are described. C57BL/6 mice were immunized with Tera-2 embryonal carcinoma cells, and hybridomas were isolated and tested versus a set of human developmental tumor cell lines. The antigens exhibit relativel

  11. Human GV oocytes generated by mitotically active germ cells obtained from follicular aspirates.

    Science.gov (United States)

    Ding, Xinbao; Liu, Guishu; Xu, Bo; Wu, Changqing; Hui, Ning; Ni, Xin; Wang, Jian; Du, Meirong; Teng, Xiaoming; Wu, Ji

    2016-01-01

    Human female germline stem cells (FGSCs) have opened new opportunities for understanding human oogenesis, delaying menopause, treating infertility, and providing a new strategy for preserving fertility. However, the shortage of adult human ovaries tissues available impedes their future investigations and clinical applications. Here, we have established FGSC lines from scarce ovarian cortical tissues that exist in follicular aspirates (faFGSCs), which are produced and discarded in in vitro fertilization centers worldwide. The faFGSCs have characteristics of germline stem cells involved in the gene expression profile, growth characteristics, and a normal karyotype consistent with that of FGSCs obtained from ovarian cortexes surgically removed from patients (srFGSCs). Furthermore, faFGSCs have developmental potentials including spontaneous differentiation into oocytes under feeder-free conditions, communicating with granulosa cells by gap junctions and paracrine factors, entering meiosis after RA induction, as well as forming follicles after injection into human ovarian cortical tissues xenografted into adult immunodeficient female mice. Lastly, we developed a strategy guiding FGSCs differentiated into germinal vesicle (GV) stage oocytes in vitro and revealed their developmental mechanisms. Our study not only provides a new approach to obtain human FGSCs for medical treatment, but also opens several avenues to investigate human oogenesis in vitro. PMID:27357640

  12. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, David M; Nielsen, John E; Skakkebaek, Niels E;

    2008-01-01

    UTF-1 and REX-1/ZFP42 are transcription factors involved in pluripotency. Because of phenotypic similarities between pluripotent embryonic stem cells and testicular germ cell tumours (TGCT) and the derivation of pluripotent cells from testes, we investigated the expression of UTF-1 and REX-1 duri...

  13. MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans

    OpenAIRE

    Irma Virant-Klun; Anders Ståhlberg; Mikael Kubista; Thomas Skutella

    2016-01-01

    MicroRNAs are a family of naturally occurring small noncoding RNA molecules that play an important regulatory role in gene expression. They are suggested to regulate a large proportion of protein encoding genes by mediating the translational suppression and posttranscriptional control of gene expression. Recent findings show that microRNAs are emerging as important regulators of cellular differentiation and dedifferentiation, and are deeply involved in developmental processes including human ...

  14. Novel strong tissue specific promoter for gene expression in human germ cells

    Directory of Open Access Journals (Sweden)

    Kuzmin Denis

    2010-08-01

    Full Text Available Abstract Background Tissue specific promoters may be utilized for a variety of applications, including programmed gene expression in cell types, tissues and organs of interest, for developing different cell culture models or for use in gene therapy. We report a novel, tissue-specific promoter that was identified and engineered from the native upstream regulatory region of the human gene NDUFV1 containing an endogenous retroviral sequence. Results Among seven established human cell lines and five primary cultures, this modified NDUFV1 upstream sequence (mNUS was active only in human undifferentiated germ-derived cells (lines Tera-1 and EP2102, where it demonstrated high promoter activity (~twice greater than that of the SV40 early promoter, and comparable to the routinely used cytomegaloviral promoter. To investigate the potential applicability of the mNUS promoter for biotechnological needs, a construct carrying a recombinant cytosine deaminase (RCD suicide gene under the control of mNUS was tested in cell lines of different tissue origin. High cytotoxic effect of RCD with a cell-death rate ~60% was observed only in germ-derived cells (Tera-1, whereas no effect was seen in a somatic, kidney-derived control cell line (HEK293. In further experiments, we tested mNUS-driven expression of a hyperactive Sleeping Beauty transposase (SB100X. The mNUS-SB100X construct mediated stable transgene insertions exclusively in germ-derived cells, thereby providing further evidence of tissue-specificity of the mNUS promoter. Conclusions We conclude that mNUS may be used as an efficient promoter for tissue-specific gene expression in human germ-derived cells in many applications. Our data also suggest that the 91 bp-long sequence located exactly upstream NDUFV1 transcriptional start site plays a crucial role in the activity of this gene promoter in vitro in the majority of tested cell types (10/12, and an important role - in the rest two cell lines.

  15. Expression Profile of a Novel Germ Cell-specific Gene, TSCPA, in Mice and Human

    Institute of Scientific and Technical Information of China (English)

    Zhendong YU; Bo WU; Aifa TANG; Jing CHEN; Xin GUO; Jie QIN; Yaoting GUI; Zhiming CAI

    2009-01-01

    In order to identify novel genes involved in spermatogenesis, testis cDNA samples from Balb/C mice of different postnatal days were hybridized with the whole mouse genome Affymetrix chip to screen the testis-specific genes. The characteristics of the selected genes were analyzed by RT-PCR as well as other bioinformatic tools. A novel differentially expressed testis-specific gene (GenBank Acces-sion No: NM_029042) in the developmental stages of testes was identified, and named TSCPA. Cellular mapping prediction of TSCPA indicated that its protein was probably expressed in nuclei, and one puta-tive domain (aa 332-377) was anchoring domain of cAMP-dependent type Ⅱ PK. The result of subcel-lular localization of GFP-TSCPA fusion protein in Cos-7 cells showed that TSCPA protein was ex-pressed in nuclei. RT-PCR analysis revealed that TSCPA was expressed specifically in mouse and hu-man testis. TSCPA gene was expressed weakly in 21-day-old mouse testis and the expression was in-creased gradually from 38th day to 6th month of mouse testes. No expression of hTSCPA was found in cryptorchidism and Sertoli-cell-only syndrome patients. It was concluded that the expression profile of TSCPA in human and mice indicated that TSCPA might play an important role in spermatogenesis.

  16. Fish germ cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Fish, like many other animals, have two major cell lineages, namely the germline and soma. The germ-soma separation is one of the earliest events of embryonic development. Germ cells can be specifically labeled and isolated for culture and transplan-tation, providing tools for reproduction of endangered species in close relatives, such as surrogate production of trout in salmon. Haploid cell cultures, such as medaka haploid embryonic stem cells have recently been obtained, which are capable of mimicking sperm to produce fertile offspring, upon nuclear being directly transferred into normal eggs. Such fish originated from a mosaic oocyte that had a haploid meiotic nucleus and a transplanted haploid mitotic cell culture nucleus. The first semi-cloned fish is Holly. Here we review the current status and future directions of understanding and manipulating fish germ cells in basic research and reproductive technology.

  17. Genome-wide assessment of the association of rare and common copy number variations to testicular germ cell cancer

    DEFF Research Database (Denmark)

    Edsgard, Stefan Daniel; Dalgaard, Marlene Danner; Weinhold, Nils;

    2013-01-01

    Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms, largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of CNV on a cohort of 212...... cases and 437 controls from Denmark, which was genotyped at ∼1.8 million markers, half of which were non-polymorphic copy number markers. No association of common variants were found, whereas analysis of rare variants (present in less than 1% of the samples) initially indicated a single gene...... of rare CNVs related to cell migration (false-discovery rate = 0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution...

  18. Stem cell pluripotency factor NANOG is expressed in human fetal gonocytes, testicular carcinoma in situ and germ cell tumours

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Almstrup, K; Nielsen, J E;

    2005-01-01

    AIMS: NANOG is a key regulator of embryonic stem cell (ESC) self-renewal and pluripotency. Our recent genome-wide gene expression profiling study of the precursor of testicular germ cell tumours, carcinoma in situ testis (CIS), showed close similarity between ESC and CIS, including high NANOG...... earlier than for OCT-4. We detected no expression at the protein level in normal testis. CONCLUSIONS: NANOG is a new marker for testicular CIS and germ cell tumours and the high level of NANOG along with OCT-4 are determinants of the stem cell-like pluripotency of the preinvasive CIS cell. Timing of NANOG......; seminoma and embryonal carcinoma were strongly positive, differentiated somatic elements of teratoma were negative. We provide evidence for the fetal origin of testicular cancer as we detected strong expression of NANOG in fetal gonocytes up to gestational week 20, with subsequent down-regulation occurring...

  19. Human primordial germ cells migrate along nerve fibers and Schwann cells from the dorsal hind gut mesentery to the gonadal ridge

    DEFF Research Database (Denmark)

    Møllgård, Kjeld; Jespersen, Åse; Lutterodt, Melissa Catherine;

    2010-01-01

    The aim of this study was to investigate the spatiotemporal development of autonomic nerve fibers and primordial germ cells (PGCs) along their migratory route from the dorsal mesentery to the gonadal ridges in human embryos using immunohistochemical markers and electron microscopy. Autonomic nerve...... PGCs arrive at the gonadal ridge between 29 and 33 days pc. In conclusion, our data suggest that PGCs in human embryos preferentially migrate along autonomic nerve fibers from the dorsal mesentery to the developing gonad where they are delivered via a fine nerve plexus....

  20. Is Tobacco Smoke a Germ-Cell Mutagen?

    Science.gov (United States)

    Although no international organization exists to declare whether an agent is a germ-cell mutagen, tobacco smoke may be a human germ-cell mutagen. In the mouse, tobacco smoke induces a significant increase in the mutation frequency at an expanded simple tandem repeat (ESTR) locus....

  1. Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model

    Science.gov (United States)

    Shimada, Atsuko; Shima, Akihiro; Nojima, Kumie; Seino, Yo; Setlow, Richard B.

    2005-04-01

    Astronauts beyond the Earth's orbit are exposed to high-energy cosmic-ray nuclei with high values of linear energy transfer (LET), resulting in much more biological damage than from x-rays or -rays and may result in mutations and cancer induction. The relative biological effectiveness of these nuclei depends on the LET, rising to as high as 50 at LET values of 100-200 keV/µm. An endpoint of concern is germ cell mutations passed on to offspring, arising from exposure to these nuclei. A vertebrate model for germ cell mutation is Medaka fish (Oryzias latipes). We exposed wild type males to doses of 1 GeV per nucleon Fe nuclei or to 290 MeV per nucleon C nuclei. They were mated to females with recessive mutations at five-color loci. The transparent embryos from >100 days of mating (representing exposed sperm, spermatids, or spermatogonia) were observed so as to detect dominant lethal mutations and total color mutations, even though the embryos might not hatch. The relative number of mutant embryos as a function of dose were compared with those induced by -rays. The relative biological effectiveness values for dominant lethal mutations and total color mutations for exposed sperm and spermatids were 1.3-2.1 for exposure to C nuclei and 1.5-3.0 for exposure to Fe nuclei. (The spermatogonial data were uncertain.) These low values, and the negligible number of viable mutations, compared with those for mutations in somatic cells and for neoplastic transformation, indicate that germ cell mutations arising from exposures to cosmic ray nuclei are not a significant hazard to astronauts. astronaut hazards | linear energy transfer | relative biological effect

  2. Germ cell mutagenesis in medaka fish after exposures to high-energy cosmic ray nuclei: A human model

    OpenAIRE

    Shimada, Atsuko; Shima, Akihiro; Nojima, Kumie; Seino, Yo; Setlow, Richard B.

    2005-01-01

    Astronauts beyond the Earth's orbit are exposed to high-energy cosmic-ray nuclei with high values of linear energy transfer (LET), resulting in much more biological damage than from x-rays or γ-rays and may result in mutations and cancer induction. The relative biological effectiveness of these nuclei depends on the LET, rising to as high as ≈50 at LET values of ≈100-200 keV/μm. An endpoint of concern is germ cell mutations passed on to offspring, arising from exposure to these nuclei. A vert...

  3. Characteristic promoter hypermethylation signatures in male germ cell tumors

    Directory of Open Access Journals (Sweden)

    Bosl George J

    2002-11-01

    Full Text Available Abstract Background Human male germ cell tumors (GCTs arise from undifferentiated primordial germ cells (PGCs, a stage in which extensive methylation reprogramming occurs. GCTs exhibit pluripotentality and are highly sensitive to cisplatin therapy. The molecular basis of germ cell (GC transformation, differentiation, and exquisite treatment response is poorly understood. Results To assess the role and mechanism of promoter hypermethylation, we analyzed CpG islands of 21 gene promoters by methylation-specific PCR in seminomatous (SGCT and nonseminomatous (NSGCT GCTs. We found 60% of the NSGCTs demonstrating methylation in one or more gene promoters whereas SGCTs showed a near-absence of methylation, therefore identifying distinct methylation patterns in the two major histologies of GCT. DNA repair genes MGMT, RASSF1A, and BRCA1, and a transcriptional repressor gene HIC1, were frequently methylated in the NSGCTs. The promoter hypermethylation was associated with gene silencing in most methylated genes, and reactivation of gene expression occured upon treatment with 5-Aza-2' deoxycytidine in GCT cell lines. Conclusions Our results, therefore, suggest a potential role for epigenetic modification of critical tumor suppressor genes in pathways relevant to GC transformation, differentiation, and treatment response.

  4. Testicular germ cell tumors and related research from a historical point of view

    DEFF Research Database (Denmark)

    Damjanov, Ivan; Albrechtsen, Nicolai Jacob Wewer

    2013-01-01

    In this brief overview of the history of testicular germ cell tumors, we touch upon the key events and personalities that have contributed to our current understanding of germ cell tumors in general, and those of the testis in particular. The intricacies of human germ cell tumor pathology...

  5. Urethral metastasis from non-seminomatous germ cell tumor: a case report

    Directory of Open Access Journals (Sweden)

    Joffe Johnathan

    2011-01-01

    Full Text Available Abstract Introduction We present a case of nonseminomatous germ cell tumor of the testes with acute urinary retention secondary to urethral metastasis. This presentation, and similar cases of urethral metastasis from this tumor, have not been reported previously. Case presentation A 35-year-old Caucasian man presented to hospital with a history of acute urinary retention. On examination he was found to have right testicular enlargement with raised β-human chorionic gonadotrophin, serum α-fetoprotein and lactate dehydrogenase levels. He underwent radical left inguinal orchidectomy and histology confirmed a nonseminomatous germ cell tumor of the testes. Cystoscopy carried out due to urinary retention showed penile metastasis and the biopsy confirmed metastatic malignant undifferentiated teratoma. Staging computed tomography scan and magnetic resonance imaging of the pelvis showed pulmonary, pelvic nodal, ischial and penile metastasis. The diagnosis of the International Germ Cell Cancer Collaborative Group of poor prognosis metastatic nonseminomatous germ cell tumor was made, following which he received four cycles of bleomycin, etoposide and cisplatin chemotherapy with curative intent. He had a complete marker and an excellent radiological response. He is currently under follow up. Conclusion The unusual presentation of lymphovascular spread in this case of nonseminomatous germ cell tumor highlights the need to include routine pelvic imaging in the assessment and follow up of testicular cancer.

  6. Human Hepatocyte-Derived Induced Pluripotent Stem Cells: MYC Expression, Similarities to Human Germ Cell Tumors, and Safety Issues

    Directory of Open Access Journals (Sweden)

    Carmen Unzu

    2016-01-01

    Full Text Available Induced pluripotent stem cells (iPSC are a most promising approach to the development of a hepatocyte transplantable mass sufficient to induce long-term correction of inherited liver metabolic diseases, thus avoiding liver transplantation. Their intrinsic self-renewal ability and potential to differentiate into any of the three germ layers identify iPSC as the most promising cell-based therapeutics, but also as drivers of tumor development. Teratoma development currently represents the gold standard to assess iPSC pluripotency. We analyzed the tumorigenic potential of iPSC generated from human hepatocytes (HEP-iPSC and compared their immunohistochemical profiles to that of tumors developed from fibroblast and hematopoietic stem cell-derived iPSC. HEP-iPSC generated tumors significantly presented more malignant morphological features than reprogrammed fibroblasts or CD34+ iPSC. Moreover, the protooncogene myc showed the strongest expression in HEP-iPSC, compared to only faint expression in the other cell subsets. Random integration of transgenes and the use of potent protooncogenes such as myc might be a risk factor for malignant tumor development if hepatocytes are used for reprogramming. Nonviral vector delivery systems or reprogramming of cells obtained from less invasive harvesting methods would represent interesting options for future developments in stem cell-based approaches for liver metabolic diseases.

  7. Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors

    Science.gov (United States)

    2015-06-11

    Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  8. Germ Cell Nuclear Factor (GCNF) Represses Oct4 Expression and Globally Modulates Gene Expression in Human Embryonic Stem (hES) Cells.

    Science.gov (United States)

    Wang, Hongran; Wang, Xiaohong; Xu, Xueping; Kyba, Michael; Cooney, Austin J

    2016-04-15

    Oct4 is considered a key transcription factor for pluripotent stem cell self-renewal. It binds to specific regions within target genes to regulate their expression and is downregulated upon induction of differentiation of pluripotent stem cells; however, the mechanisms that regulate the levels of human Oct4 expression remain poorly understood. Here we show that expression of human Oct4 is directly repressed by germ cell nuclear factor (GCNF), an orphan nuclear receptor, in hES cells. Knockdown of GCNF by siRNA resulted in maintenance of Oct4 expression during RA-induced hES cell differentiation. While overexpression of GCNF promoted repression of Oct4 expression in both undifferentiated and differentiated hES cells. The level of Oct4 repression was dependent on the level of GCNF expression in a dose-dependent manner. mRNA microarray analysis demonstrated that overexpression of GCNF globally regulates gene expression in undifferentiated and differentiated hES cells. Within the group of altered genes, GCNF down-regulated 36% of the genes, and up-regulated 64% in undifferentiated hES cells. In addition, GCNF also showed a regulatory gene pattern that is different from RA treatment during hES cell differentiation. These findings increase our understanding of the mechanisms that maintain hES cell pluripotency and regulate gene expression during the differentiation process.

  9. 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

    , human gp36, T1A-2), a transmembrane glycoprotein expressed in lymphatic endothelium and various solid tumours. To examine a potential role for PDPN in testicular neoplasms and during testicular development, we investigated its expression pattern during the development of human testis and in a series of...... function in developing testis, most likely at the level of cell-cell interactions among pre-meiotic germ cells and immature Sertoli cells....

  10. Carcinoma in situ of the testis. Some ultrastructural characteristics of germ cells

    DEFF Research Database (Denmark)

    Albrechtsen, R; Nielsen, M H; Skakkebaek, N E;

    1982-01-01

    The two cytoplasmic organelles, dense-cored vesicles and "nuages" have been considered to allow positive identification of primordial germ cells in rodents, but no use of these potential markers has been applied to human material. We have observed dense-cored vesicles and "nuages" in the abnormal...... germ cells of carcinoma in situ of the testis and thus brought further evidence for the germ cell origin of this lesion. These organelles may be useful cytoplasmic markers in the study of germ cell tumors....

  11. Mechanisms and chemical induction of aneuploidy in rodent germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Mailhes, J B; Marchetti, F

    2004-10-15

    The objective of this review is to suggest that the advances being made in our understanding of the molecular events surrounding chromosome segregation in non-mammalian and somatic cell models be considered when designing experiments for studying aneuploidy in mammalian germ cells. Accurate chromosome segregation requires the temporal control and unique interactions among a vast array of proteins and cellular organelles. Abnormal function and temporal disarray among these, and others to be inidentified, biochemical reactions and cellular organelles have the potential for predisposing cells to aneuploidy. Although numerous studies have demonstrated that certain chemicals (mainly those that alter microtubule function) can induce aneuploidy in mammalian germ cells, it seems relevant to point out that such data can be influenced by gender, meiotic stage, and time of cell-fixation post-treatment. Additionally, a consensus has not been reached regarding which of several germ cell aneuploidy assays most accurately reflects the human condition. More recent studies have shown that certain kinase, phosphatase, proteasome, and topoisomerase inhibitors can also induce aneuploidy in rodent germ cells. We suggest that molecular approaches be prudently incorporated into mammalian germ cell aneuploidy research in order to eventually understand the causes and mechanisms of human aneuploidy. Such an enormous undertaking would benefit from collaboration among scientists representing several disciplines.

  12. Presumed pluripotency markers UTF-1 and REX-1 are expressed in human adult testes and germ cell neoplasms

    DEFF Research Database (Denmark)

    Kristensen, D.M.; Nielsen, J.E.; Skakkebaek, N.E.;

    2008-01-01

    NANOG and OCT-3/4, UTF-1 and REX-1 are expressed throughout human testes development. The expression pattern indicated that UTF-1 plays a possible role in spermatogonial self-renewal, whereas expression of REX-1 in meiotic cells from both testes and ovary indicate a role in meiosis. UFT-1 and REX-1...

  13. Enhancement of mouse germ cell-associated genes expression by injection of human umbilical cord mesenchymal stem cells into the testis of chemical-induced azoospermic mice

    Institute of Scientific and Technical Information of China (English)

    RuiFeng Yang; TaiHua Liu; Kai Zhao; ChengLiang Xiong

    2014-01-01

    Various methods are currently under investigation to preserve fertility in males treated with high‑dose chemotherapy and radiation for malignant and nonmalignant disorders. Human umbilical cord mesenchymal stem cells(HUC‑MSCs), which possess potent immunosuppressive function and secrete various cytokines and growth factors, have the potential clinical applications. As a potential alternative, we investigate whether injection of HUC‑MSCs into the interstitial compartment of the testes to promote spermatogenic regeneration efifciently. HUC‑MSCs were isolated from different sources of umbilical cords and injected into the interstitial space of one testis from 10 busulfan‑treated mice(saline and HEK293cells injections were performed in a separate set of mice) and the other testis remained uninjected. Three weeks after MSCs injection, Relative quantitative reverse transcription polymerase chain reaction was used to identify the expression of 10 of germ cell associated, which are all related to meiosis, demonstrated higher levels of spermatogenic gene expression(2–8 fold) in HUC‑MSCs injected testes compared to the contralateral uninjected testes(ifve mice). Protein levels for germ cell‑speciifc genes,miwi, vasa and synaptonemal complex protein (Scp3)were also higher in MSC‑treated testes compared to injected controls 3weeks after treatment. However, no different expression was detected in saline water and HEK293cells injection control group. We have demonstrated HUC‑MSCs could affect mouse germ cell‑speciifc genes expression. The results also provide a possibility that the transplanted HUC‑MSCs may promote the recovery of spermatogenesis. This study provides further evidence for preclinical therapeutic effects of HUC‑MSCs, and explores a new approach to the treatment of azoospermia.

  14. [Ovarian germ cell tumors in girls].

    Science.gov (United States)

    Nechushkina, I V; Karseladze, A I

    2015-01-01

    Morphological structure of tumor influences on the clinical course of the disease in children with germ cell tumors. Patients with ovarian dysgerminoma at the time of diagnosis are significantly older than patients with immature teratoma and yolk sac tumor. Immature teratoma and mixed germ cell tumors are significantly larger compared to other germ cell tumors. Yolk sac tumor and embryonal carcinoma are the most common cause of emergency surgical interventions and are accompanied by rupture of tumor capsule. PMID:26087605

  15. Analysis of the DNDI gene in men with sporadic and familial testicular germ cell tumors

    NARCIS (Netherlands)

    Linger, Rachel; Dudakia, Darshna; Huddart, Robert; Tucker, Kathy; Friedlander, Michael; Phillips, Kelly-Anne; Hogg, David; Jewett, Michael A. S.; Lohynska, Radka; Daugaard, Gedske; Richard, Stephane; Chompret, Agnes; Stoppa-Lyonnet, Dominique; Bonaiti-Pellie, Catherine; Heidenreich, Axel; Albers, Peter; Olah, Edith; Geczi, Lajos; Bodrogi, Istvan; Daly, Peter A.; Guilford, Parry; Fossi, Sophie D.; Heimdal, Ketil; Tjulandin, Sergei A.; Liubchenko, Ludmila; Stoll, Hans; Weber, Walter; Einhorn, Lawrence; McMaster, Mary; Korde, Larissa; Greene, Mark H.; Nathanson, Katherine L.; Cortessis, Victoria; Easton, Douglas F.; Bishop, D. Timothy; Stratton, Michael R.; Rapley, Elizabeth A.

    2008-01-01

    A base substitution in the mouse DndI gene resulting in a truncated Dnd protein has been shown to be responsible for germ cell loss and the development of testicular germ cell tumors (TGCT) in the 129 strain of mice. We investigated the human orthologue of this gene in 263 patients (165 with a famil

  16. Role of metallothionein in cisplatin sensitivity of germ-cell tumours

    NARCIS (Netherlands)

    Meijer, C.; Timmer, A.; Vries, E.G.E.de; Groten, J.P.; Knol, A.; Zwart, N.; Dam, W.A.; Sleijfer, D.Th.; Mulder, N.H.

    2000-01-01

    Cisplatin (CDDP) is an extremely active drug in the treatment of germ- cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ-cell tumour and 3 colon-carcinoma cell lines. Major components of the

  17. Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study

    DEFF Research Database (Denmark)

    Fizazi, K.; Oldenburg, J.; Dunant, A.;

    2008-01-01

    BACKGROUND: The purpose of this study was to validate a prognostic index [surgical complete response 1 (sCR1)] in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: Data and specimens from 61 patients with normalized tumor markers and postchemoth......BACKGROUND: The purpose of this study was to validate a prognostic index [surgical complete response 1 (sCR1)] in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: Data and specimens from 61 patients with normalized tumor markers...... malignant cells, and a good International Germ Cell Consensus Classification group at presentation. Patients were assigned to one of three risk groups defined in sCR1: no risk factor (good risk), one risk factor (intermediate risk) and two to three risk factors (poor risk group). The 5-year PFS rate was 92......%, 78%, and 42%, respectively (P = 0.002) (as compared with 90%, 76%, and 41% in the original sCR1 study). The 5-year OS rate was 90%, 86%, and 52%, respectively (P = 0.009) (as compared with 100%, 83%, and 51% in the original sCR1 study). Postoperative chemotherapy did not appear to improve OS compared...

  18. Atypical extragonadal germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mainak Deb

    2012-01-01

    Full Text Available Aim: To review the experience with the diagnosis and management of extragonadal germ cell tumors (GCT with a subset analysis of those with atypical features. Materials and Methods: A retrospective chart review of patients of extragonadal germ cell tumors between 2000 and 2010 was carried out. Results: Fifteen children aged 7 days to 15 years (median, 1.5 years were included. Three had an antenatal diagnosis (one sacrococcygeal, one retrobulbar, one retroperitoneal tumor and were operated in the neonatal period. The locations were distributed between the retrobulbar area (1, anterior neck-thyroid gland (1, mediastinum (4, abdominothoracic extending through the esophageal hiatus (1, retroperitoneal (4 and sacrococcygeal (4. On histological examination, five harbored immature elements while two were malignant; the latter children received postexcision adjuvant chemotherapy. There was no mortality. At a median follow-up of 4.5 years (6 months to 8 years, 14/15 have had an event-free survival. One immature mediastinal teratoma that recurred locally 7.5 years after the initial operation was excised and adjuvant chemotherapy instituted. Conclusions: Extragonadal GCTs in children are uncommon and occasionally present with atypical clinical, radiological and histological features resulting in diagnostic and therapeutic dilemmas.

  19. Genetic analysis of neonatal and infantile germ cell tumours

    NARCIS (Netherlands)

    Veltman, I.M.

    2006-01-01

    Human germ cell tumours (GCTs) can be classified into five distinct types, based on differences in anatomical location, histology, clinical outcome, age and genotype. The first type, the type I GCTs primarily occur in neonates and infants under the age of five years and include teratomas and yolk sa

  20. Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

    DEFF Research Database (Denmark)

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

    2001-01-01

    of infertility. In order to increase the number of germ cells, and thereby the fertility potential, additional hormonal therapy has been attempted before surgery. In a study, small doses of the gonadotropin-releasing hormone analogue buserelin before orchiopexy caused higher values. Others have found......PURPOSE: In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10-40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33-100% risk...... that hormonal treatment with human chorionic gonadotropin or gonadotropin releasing hormone analogue may harm the germ cells in cryptorchidism. The aim of the study is to demonstrate that additional hormonal therapy with erythropoietin has a positive effect on the number of germ cells. MATERIALS AND METHODS...

  1. Delayed BMP4 exposure increases germ cell differentiation in mouse embryonic stem cells.

    Science.gov (United States)

    Talaei-Khozani, Tahereh; Zarei Fard, Nehleh; Bahmanpour, Soghra; Jaberipour, Mansoureh; Hosseini, Ahmah; Esmaeilpour, Tahereh

    2014-01-01

    Fate mapping studies have revealed that bone morphogenetic protein 4 (BMP4) signaling has a key role in segregation of primordial germ cells from proximal epiblast. Adding BMP4 to the culture media of embryonic stem (ES) cells could induce expression of germ cell markers; however, to provide a desired number of germ cells has remained a challenge. In the current study, we intended to establish an in vitro system to obtain reliable germ cells derived from ES cells. Differentiation was induced in ES cells via embryoid body (EB) and monolayer culture system. Cells were cultured with BMP4 from the beginning (++BMP4) or after 48 hours (+BMP4) of culturing for five days. The cultures were assessed for alkaline phosphatase (ALP) activity, expression of Oct4, Mvh and c-kit. In EB culture protocol, the expression of Mvh, Oct4 and ALP activity significantly increased in +BMP4 culture condition, but a significant down-regulation in the expression of germ cell markers was shown in ++BMP4 condition compared with the control group. Parallel differentiation experiments using monolayer culture system indicated the number of putative germ cells did not change. In the current study, we compared two differentiation methods (EB and monolayer) to achieve an optimal germ cell production. The EBs with a short exposure time period to BMP4, showing typical characteristics of germ cells. Therefore, our approach provides a strategy for the production of germline cells from ES cells. PMID:24969978

  2. Tritium effects on germ cells and fertility

    International Nuclear Information System (INIS)

    Primordial oocytes in juvenile mice show acute gamma-ray LD50 as low as 6 rad. This provides opportunities for determining dose-response relations at low doses and chronic exposure in the intact animal - conditions of particular interest for hazard evaluation. Examined in this way, 3HOH in body water is found to kill murine oocytes exponentially with dose, the LD50 level for chronic exposure being only 2μCi/ml (delivering 0.4 rad/day). At very low doses and dose rates, where comparisons between tritium and other radiations are of special significance for radiological protection, the RBE of tritium compared with 60Co gamma radiation reaches approximately 3. Effects on murine fertility from tritium-induced oocyte loss have been quantified by reproductive capacity measurements. Chronic low-level exposure has been examined also in three primate species - squirrel, rhesus, and bonnet monkeys. In squirrel monkeys the ovarian germ-cell supply is 99% destroyed by the time of birth from prenatal exposure to body-water levels of 3HOH (administered in maternal drinking water) of only 3 μCi/ml, the LD50 level being 0.5 μCi/ml (giving 0.1 rad/day), one fourth that in mice. Though not completely ruled out, similar high sensitivity of female germ cells has not been found in macaques; and it probably does not occur in man. The exquisite radiosensitivity of primordial oocytes in mice is apparently due to vulnerability of the plasma membrane (or something of similar geometry and location), not DNA. Evidence for this comes from tritium data as well as neutron studies. Tritium administered as 3HOH, and therefore generally distributed, is much more effective in killing murine oocytes than is tritium administered as 3H-TdR, localized in the nucleus. This situation in the mouse may have implications for estimating radiation genetic risk in the human female

  3. Germ cell specification and regeneration in planarians.

    Science.gov (United States)

    Newmark, P A; Wang, Y; Chong, T

    2008-01-01

    In metazoans, two apparently distinct mechanisms specify germ cell fate: Determinate specification (observed in animals including Drosophila, Caenorhabditis elegans, zebra fish, and Xenopus) uses cytoplasmic factors localized to specific regions of the egg, whereas epigenetic specification (observed in many basal metazoans, urodeles, and mammals) involves inductive interactions between cells. Much of our understanding of germ cell specification has emerged from studies of model organisms displaying determinate specification. In contrast, our understanding of epigenetic/inductive specification is less advanced and would benefit from studies of additional organisms. Freshwater planarians--widely known for their remarkable powers of regeneration--are well suited for studying the mechanisms by which germ cells can be induced. Classic experiments showed that planarians can regenerate germ cells from body fragments entirely lacking reproductive structures, suggesting that planarian germ cells could be specified by inductive signals. Furthermore, the availability of the genome sequence of the planarian Schmidtea mediterranea, coupled with the animal's susceptibility to systemic RNA interference (RNAi), facilitates functional genomic analyses of germ cell development and regeneration. Here, we describe recent progress in studies of planarian germ cells and frame some of the critical unresolved questions for future work.

  4. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Skakkebaek, N E

    1994-01-01

    Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study......, CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect...... in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells...

  5. General Information about Extragonadal Germ Cell Tumors

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  6. Treatment Option Overview (Extragonadal Germ Cell Tumors)

    Science.gov (United States)

    ... following PDQ summaries: Ovarian Germ Cell Tumors Treatment Testicular Cancer Treatment Age and gender can affect the risk ... summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and ...

  7. Stages of Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  8. Dissecting Germ Cell Metabolism through Network Modeling.

    Directory of Open Access Journals (Sweden)

    Leanne S Whitmore

    Full Text Available Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA. Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health.

  9. Germ cell transplantation in infertility mouse

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This work investigated the spermatogenesis in an infertility BALB/c-nu mouse model by reinfusing germline stem cells into seminiferous tubules.Donor germ cells were isolated from male FVB/NJ-GFP transgenic mice.Seminiferous tubule microiniection was applied to achieve intratubular germ cell transfer.The germ cells were injected into exposed testes of the infertility mice.We used green fluorescence and DNA analysis of donor cells from GFP transgenic mice as genetic marker.The natural mating and Southern blot methods were applied to analyze the effect of sperm cell transplantation and the sperm function after seminiferous tubule microinjecUon.The spermatogenesis was morphologically observed from the seminiferous tubules in 41/60(68.33%)of the injected recipient mice using allogeneic donor cells.In the colonized testes,matured spermatozoa were seen in the lumen of the seminiferous tubules.In this research,BALB/c-nu infertility mouse model,the recipient animal,was used to avoid immunological rejection of donor cells,and germ cell transplantation was applied to overcome infertility caused by busulfan treatment.These results demonstrate that this technique of germ cell transplantation is of great use.Germ cell transplantation could be potentially valuable to oncological patients.

  10. The role of sex chromosomes in mammalian germ cell differentiation: can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes?

    Directory of Open Access Journals (Sweden)

    Teruko Taketo

    2015-06-01

    Full Text Available The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.

  11. New evidence for the origin of intracranial germ cell tumours from primordial germ cells

    DEFF Research Database (Denmark)

    Hoei-Hansen, C E; Sehested, A; Juhler, M;

    2006-01-01

    with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting...

  12. Human second trimester amniotic fluid cells are able to create embryoid body-like structures in vitro and to show typical expression profiles of embryonic and primordial germ cells.

    Science.gov (United States)

    Antonucci, Ivana; Di Pietro, Roberta; Alfonsi, Melissa; Centurione, Maria Antonietta; Centurione, Lucia; Sancilio, Silvia; Pelagatti, Francesca; D'Amico, Maria Angela; Di Baldassarre, Angela; Piattelli, Adriano; Tetè, Stefano; Palka, Giandomenico; Borlongan, Cesar V; Stuppia, Liborio

    2014-01-01

    Human amniotic fluid-derived stem cells (AFSCs) represent a novel class of broadly multipotent stem cells sharing characteristics of both embryonic and adult stem cells. However, both the origin of these cells and their actual properties in terms of pluripotent differentiation potential are still debated. In order to verify the presence of features of pluripotency in human second trimester AFSCs, we have investigated the ability of these cells to form in vitro three-dimensional aggregates, known as embryoid bodies (EBs), and to express specific genes of embryonic stem cells (ESCs) and primordial germ cells (PGCs). EBs were obtained after 5 days of AFSC culture in suspension and showed positivity for alkaline phosphatase (AP) staining and for specific markers of pluripotency (OCT4 and SOX2). Moreover, EB-derived cells showed the expression of specific transcripts of the three germ layers. RT-PCR analysis, carried out at different culture times (second, third, fourth, fifth, and eighth passages), revealed the presence of specific markers of ESCs (such as FGF4 and DAPPA4), as well as of markers typical of PGCs and, in particular, genes involved in early stages of germ cell development (Fragilis, Stella, Vasa, c-Kit, Rnf17). Finally, the expression of genes related to the control of DNA methylation (DNMT3A, DNMT3b1, DNMT1, DNMT3L, MBD1, MBD2, MBD3, MDB4, MeCP2), as well as the lack of inactivation of the X-chromosome in female samples, was also demonstrated. Taken together, these data provide further evidence for the presence of common features among human AFSCs, PGCs, and ESCs.

  13. MR imaging findings of pineal germinoma: focus on differential diagnosis from other germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Jin; Lee, Ho Kyu; Kim, Jae Kyun; Shin, Ji Hoon; Choi, Choong Gon; Lee, Myung Jun; Ham, Soo Youn; Lee, Jong Hwa; Suh, Dae Chul [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    To determine the characteristic MR imaging findings of pineal germinoma, and differential diagnosis from other germ cell tumors. MR images of patients with histopathologically proven pineal germinoma(n=3D14) and other pineal germ cell tumors(n=3D10) were retrospectively analyzed with regard to size, signal intensity and homogeneity, enhancing features, cyst formation, and multiplicity of lesions. Other pineal germ cell tumors were the mixed germ cell tumors (n=3D4), malignant teratomas (n=3D3), choriocarcinoma(n=3D1), embryonal carcinoma(n=3D1), and endodermal sinus tumor(n=3D1). Tumor markers were evaluated. On T1-weighted images, germinomas showed homogeneous(86%) or iso signal intensity (93%), while other germ cell tumors showed inhomogeneous(70%) or iso signal intensity(70%). On T2-weighted images, germinomas showed homogeneous(64%) or iso signal intensity(57%), while other germ cell tumors showed inhomogeneous(70%) or high signal intensity(80%). On Gd-DTPA enhanced images, germinomas showed homogeneous (93%) or strong enhancement (64%), while other germ cell tumors showed homogeneous(60%) or strong enhancement (70%). Cyst formation was noted in ten Patients (71%) with germinoma and in six (60%) with other germ cell tumors. Invasion on surrounding structures was seen in 11 patients (79%) with germinoma and in five (50%) with other germ cell tumors. Lesions were multiple in three patients(21%) with germinoma. Thirteen of 14 patients with germinoma had normal serum {alpha}-FP(tetoprotein) and {beta}-HCG(human chononic gonafotrophin) levels. Two of four patients with mixed germ cell tumors had elevated serum {beta}-FP and {alpha}-HCG levels; in the ther two, elevated serum {alpha}-FP or {beta}-HCG levels were noted. In the malignant teratoma and embryonal carcinoma patients, serum {alpha}-FP and {beta}-HCG levels were normal. The patient with choriocarcinoma had an elevated serum {beta}-HCG level. On T1W1, the only significant differential point (p<0.01) between

  14. Germ-cell deficient (gcd), an insertional mutation manifested as infertility in transgenic mice.

    Science.gov (United States)

    Pellas, T C; Ramachandran, B; Duncan, M; Pan, S S; Marone, M; Chada, K

    1991-10-01

    A genetic analysis is necessary to gain a greater understanding of the complex developmental processes in mammals. Toward this end, an insertional transgenic mouse mutant has been isolated that results in abnormal germ-cell development. This recessive mutation manifests as infertility in both males and females and is specific for the reproductive organs, since all other tissues examined were histologically normal. A developmental analysis of the gonadal tissues demonstrated that the germ cells were specifically depleted as early as day 11.5 of embryonic development, while the various somatic cells were apparently unaffected. Therefore, the mutated locus must play a critical role in the migration/proliferation of primordial germ cells to the genital ridges of developing embryos. In addition, females homozygous for the mutation could potentially be a valuable animal model of a human syndrome, premature ovarian failure. This mutation has been named germ-cell deficient, gcd.

  15. Germ cell development in the postnatal testis

    DEFF Research Database (Denmark)

    Hutson, John M; Li, Ruili; Southwell, Bridget R;

    2012-01-01

    To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth......, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought...... the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing...

  16. Expression of the PDGF α-receptor 1.5 kb transcript, OCT-4, and c-KIT in human normal and malignant tissues. Implications for the early diagnosis of testicular germ cell tumours and for our understanding of regulatory mechanisms

    NARCIS (Netherlands)

    C. Palumbo (Camilla); K.E. van Roozendaal (Kees); A.J.M. Gillis (Ad); R.J.H.L.M. van Gurp (Ruud); H. de Munnik (Hannie); J.W. Oosterhuis (Wolter); E.J.J. van Zoelen (Everardus); L.H.J. Looijenga (Leendert)

    2002-01-01

    textabstractHuman testicular germ cell tumours of adolescents and adults (TGCTs), including their precursor lesion carcinoma in situ (CIS), show expression of a 1.5 kb alternative transcript of the platelet-derived growth factor (PDGF) α-receptor gene. The so-called P2 promoter involved is located i

  17. Mixed malignant germ cell tumor of ovary

    OpenAIRE

    Sviračević Branko; Sedlar Srđan; Malobabić Dragan; Ćuk Dragomir

    2011-01-01

    Introduction. Malignant tumours of ovary germ epithelium are very rare and account for about 2-5% of all ovarian tumours of germ origin. In adolescent patients under 20 years of age diagnosed to have ovarian tumour, these tumours originate from germ cells in about 70% of cases. Depending on the stage of the disease, medical treatment and age, the death rate ranges from 25% to 84%. A special group of germ tumours are mixed germ cells tumours built of two or more different types of germ t...

  18. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    Science.gov (United States)

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  19. Mouse Germ Cell Development in-vivo and in-vitro

    Directory of Open Access Journals (Sweden)

    Deshira Saiti

    2007-01-01

    Full Text Available In mammalian development, primordial germ cells (PGCs represent the initial population of cells that are committed to the germ cell lineage. PGCs segregate early in development, triggered by signals from the extra-embryonic ectoderm. They are distinguished from surrounding cells by their unique gene expression patterns. Some of the more common genes used to identify them are Blimp1, Oct3/4, Fragilis, Stella, c-Kit, Mvh, Dazl and Gcna1. These genes are involved in regulating their migration and differentiation, and in maintaining the pluripotency of these cells. Recent research has demonstrated the possibility of obtaining PGCs, and subsequently, mature germ cells from a starting population of embryonic stem cells (ESCs in culture. This phenomenon has been investigated using a variety of methods, and ESC lines of both mouse and human origin. Embryonic stem cells can differentiate into germ cells of both the male and female phenotype and in one case has resulted in the birth of live pups from the fertilization of oocytes with ESC derived sperm. This fi nding leads to the prospect of using ESC derived germ cells as a treatment for sterility. This review outlines the evolvement of germ cells from ESCs in vitro in relation to in vivo events.

  20. Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Jørgensen, N; Brøndum-Nielsen, K;

    1998-01-01

    hypothesise that if the development of the testis is disturbed or delayed, primordial germ cells or gonocytes undergo maturation delay or differentiation arrest which may render them susceptible to neoplastic transformation. Morphologically homogenous premalignant carcinoma in situ (CIS) cells have...

  1. Effects of low-dose heavy ion irradiation on male germ cell adaptation and genetics

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; LI Wen-Jian; ZHENG Rong-Liang

    2005-01-01

    The heavy ions with high linear energy transfer and high relative biological effectiveness are much more deleterious on the male germ cells, ones of the most radiosensitive cells of the body, than low-LET ionizing radiation such as X-ray or gamma-ray. The effects of low-dose heavy ion irradiation on male germ cell adaptation and genetics and the possible mechanism of this adaptation are summarized in our laboratory. Our results showed that the heavy ion irradiation significantly increased the frequencies of chromosomal aberrations in spermatogonia and spermatocytes of mice, the low dose heavy ion irradiation could induce significant adaptative response on mouse testes and human sperm, and pre-exposure of mouse testes with low-dose heavy ion can markedly alleviate damage effects induced by subsequent high-dose irradiation. The increase of SOD activity and decrease of lipid peroxidation levels induced by low-dose ionizing radiation may be involved in this adaptative response mechanism. These studies may provide useful theoretical and clinical bases for radioprotection of reproductive potential and assessment of genetic risks for human exposed to heavy ions in radiotherapy and in outer space environment.

  2. Diagnostic markers for germ cell neoplasms

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E;

    2015-01-01

    -genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNAs (miRs). Testicular GCTs display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise......This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCTs), with focus on the most common testicular GCTs (TGCTs). GCTs are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic...... to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative markers for GCT, except teratoma, are genes expressed in primordial germ cell/gonocyte and embryonic pluripotency...

  3. Rebuilding Pluripotency from Primordial Germ Cells

    Science.gov (United States)

    Leitch, Harry G.; Nichols, Jennifer; Humphreys, Peter; Mulas, Carla; Martello, Graziano; Lee, Caroline; Jones, Ken; Surani, M. Azim; Smith, Austin

    2013-01-01

    Mammalian primordial germ cells (PGCs) are unipotent progenitors of the gametes. Nonetheless, they can give rise directly to pluripotent stem cells in vitro or during teratocarcinogenesis. This conversion is inconsistent, however, and has been difficult to study. Here, we delineate requirements for efficient resetting of pluripotency in culture. We demonstrate that in defined conditions, routinely 20% of PGCs become EG cells. Conversion can occur from the earliest specified PGCs. The entire process can be tracked from single cells. It is driven by leukemia inhibitory factor (LIF) and the downstream transcription factor STAT3. In contrast, LIF signaling is not required during germ cell ontogeny. We surmise that ectopic LIF/STAT3 stimulation reconstructs latent pluripotency and self-renewal. Notably, STAT3 targets are significantly upregulated in germ cell tumors, suggesting that dysregulation of this pathway may underlie teratocarcinogenesis. These findings demonstrate that EG cell formation is a robust experimental system for exploring mechanisms involved in reprogramming and cancer. PMID:24052943

  4. Germ cell apoptosis induced by progesterone in rats

    Institute of Scientific and Technical Information of China (English)

    Cui Yu-gui; Liao Ting-ting; Liu Jia-yin; Jia Yue; Cai Rui-fen; Gao Li; Wang Xing-hai; Tong Jian-sun; Ma Ding-zhi; Zhang Cai-ting; Wang Xue-song

    2007-01-01

    Objectives: To document the effect of progesterone exposure with large dose and long term on spermatogenesis,especially on the germ cell apoptosis in rats.This study was also to evaluate the toxicity of progesterone in the reproductive system when administered with large doses and long term in men.Methods: Groups of adult male SD rats were administered with 37.5, 75 and 150 mg/kg depotmedroxyprogesterone acetate (DMPA) per two-weeks for 12 or 18 weeks.At the end of treatment, each male rat was paired with one adult female SD rat to estimate the reproductive function.Serum testosterone concentration was analyzed in duplicate by radioimmunoassay (RIA).The pathological changes of testes, epididymis, and prostate were checked under light microscopic, epididymis was also used for sperm count, and fresh testis tissue was used for apoptosis assessment by flow cytometry.Results.After treatment with DMPA, weights of gonad, the ratio of testes/body, the ratio of epididymides/body,and the ratio of prostate/body decreased significantly (P<0.01).The level of serum testosterone, sperm count, sperm activity decreased significantly(P<0.01) while abnormality of sperm increased significantly (P<0.01).The embryonic number in uterus of pairing female rat decreased significantly after DMPA treatment.Compared with control, the number and the ratio of apoptotic germ cell increased dramatically (P<0.01) along with dose increase or treating prolongation of DMPA, which analyzed by flow cytometry.Conclusion: In summary, in addition to inhibition of pituitary gonadotrophin and subsequently deprivation of androgen, progesterone (DMPA)inhibits spermatogenesis by the induced germ cell apoptosis.The reproductive toxicity of DMPA administrated with large doses and long term is confirmed.

  5. Epigenetic features of testicular germ cell tumours in relation to epigenetic characteristics of foetal germ cells

    DEFF Research Database (Denmark)

    Kristensen, Dina Graae; Skakkebæk, Niels E; Rajpert-De Meyts, Ewa;

    2013-01-01

    Foetal development of germ cells is a unique biological process orchestrated by cellular specification, migration and niche development in concert with extensive epigenetic and transcriptional programs. Many of these processes take place early in foetal life and are hence very difficult to study....... In this review, we will focus on current knowledge of the epigenetics of CIS cells and relate it to the epigenetic changes occurring in early developing germ cells of mice during specification, migration and colonization. We will focus on DNA methylation and some of the best studied histone modifications like H3......K9me2, H3K27me3 and H3K9ac. We also show that CIS cells contain high levels of H3K27ac, which is known to mark active enhancers. Proper epigenetic reprogramming seems to be a pre-requisite of normal foetal germ cell development and we propose that alterations in these programs may be a pathogenic...

  6. Non-germ cell tumours arising in germ cell tumours (teratoma with malignant transformation) in men: CT and MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Athanasiou, A. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Institut Curie, Paris (France)], E-mail: alexandra.athanasiou@curie.net; Vanel, D. [Department of Radiology, Institut Gustave-Roussy, Villejuif (France); Department of Radiology, Istituti Ortopedici Rizzoli, Bologna (Italy); El Mesbahi, O. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Theodore, C. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France); Department of Oncology, Hopital Foch, Suresnes (France); Fizazi, K. [Department of Medicine, Institut Gustave-Roussy, Villejuif (France)

    2009-02-15

    Purpose: To describe the imaging findings of germ cell tumours (GCT) containing non-germ cell malignant components (also designated teratoma with malignant transformation or TMT). Patients and methods: The records of 14 male patients with GCT and a non-germ cell histological component TMT were retrospectively reviewed. All patients had computed tomography (CT) and/or magnetic resonance (MR) studies before and after initial surgery and chemotherapy, as well as during follow-up. Imaging findings were correlated with the response to treatment and with overall survival. Pathological evaluation, immunohistochemistry, serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were also taken into consideration. Sarcoma was identified in 10 out of 14 patients, with rhabdomyosarcoma ranking first (n = 4), followed by osteosarcoma (n = 2), fusiform cell sarcoma (n = 1), undifferentiated sarcoma (n = 1), neurosarcoma (n = 1) and myxoid sarcoma (n = 1). Other histological types of malignant transformation included adenocarcinoma (n = 3) and bronchoalveolar carcinoma (n = 1). Overall, 9 patients relapsed at a median time of 84 months (range 60-168). Results: Non-GCT malignant transformation was identified in the retroperitoneum (5), testis (3), mediastinum (3), peritoneum (2) and lungs (1). The CT and MR imaging findings before treatment and after relapse were evaluated with emphasis on imaging features that could possibly imply the presence of malignant transformation (heterogeneously enhancing soft-tissue masses, ossified masses with calcified lymph nodes, diffuse epiploic thickening associated with ascites and peritoneal nodules, pulmonary alveolar infiltration with septal thickening). All but 1 patient with TMT presented with nodal and distant metastases. The prognosis was poor: within a median follow-up of 59 months (range 3-180), 4 out of 14 patients were alive. Conclusion: TMT is rare and associated with poorer survival compared to GCT. Imaging can be useful

  7. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    Science.gov (United States)

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  8. Dazl Promotes Germ Cell Differentiation from Embryonic Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Zhuo Yu; Ping Ji; Jinping Cao; Shu Zhu; Yao Li; Lin Zheng; Xuejin Chen; Lixin Feng

    2009-01-01

    It has been demonstrated that through the formation of embryoid bodies (Ebs) germ cells can be derived from embryonic stem (ES) cells. Here, we describe a transgene expression approach to derive germ cells directly from ES cells in vitro without EB formation. Through the ectopic expression of Deleted in Azoospermia-Like (Dazl), a germ cell-specific RNA-binding protein,both motile tailed-sperm and oocytes were induced from mouse ES (mES) cells in culture. Furthermore, transient overexpression of Dazl led to suppression of Nanog but induced germ cell nuclear antigen in mES cells. Dazl knockdown resulted in reduction in the expression of germ cell markers including Stella, MVH and Prdm1. Our study indicates that Dazl is a master gene controlling germ cell differentiation and that ectopic expression of Dazl promotes the dynamic differentiation of mouse ES cells into gametes in vitro.

  9. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    OpenAIRE

    Sabine Conrad; Hossein Azizi; Maryam Hatami; Mikael Kubista; Michael Bonin; Jörg Hennenlotter; Karl-Dietrich Sievert; Thomas Skutella

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic ge...

  10. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice

    Energy Technology Data Exchange (ETDEWEB)

    Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert; Marchetti, Francesco; Venkatachalam, Sundaresan

    2009-06-24

    Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

  11. Germ Cell Tumors in Adolescents and Young Adults.

    Science.gov (United States)

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  12. Biology and Molecular Markers of Malignant Gonadal Germ Cell Tumors

    OpenAIRE

    Salonen, Jonna

    2009-01-01

    Germ cell tumors occur both in the gonads of both sexes and in extra-gonadal sites during adoles-cence and early adulthood. Malignant ovarian germ cell tumors are rare neoplasms accounting for less than 5% of all cases of ovarian malignancy. In contrast, testicular cancer is the most common malignancy among young males. Most of patients survive the disease. Prognostic factors of gonadal germ cell tumors include histology, clinical stage, size of the primary tumor and residua, and levels of tu...

  13. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells.

    Science.gov (United States)

    Conrad, Sabine; Azizi, Hossein; Hatami, Maryam; Kubista, Mikael; Bonin, Michael; Hennenlotter, Jörg; Sievert, Karl-Dietrich; Skutella, Thomas

    2016-01-01

    The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs) and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen-/laminin+ binding-) selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs) and human fibroblasts (hFibs) revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers. PMID:26649052

  14. Expression of Genes Related to Germ Cell Lineage and Pluripotency in Single Cells and Colonies of Human Adult Germ Stem Cells

    Directory of Open Access Journals (Sweden)

    Sabine Conrad

    2016-01-01

    Full Text Available The aim of this study was to elucidate the molecular status of single human adult germ stem cells (haGSCs and haGSC colonies, which spontaneously developed from the CD49f MACS and matrix- (collagen−/laminin+ binding- selected fraction of enriched spermatogonia. Single-cell transcriptional profiling by Fluidigm BioMark system of a long-term cultured haGSCs cluster in comparison to human embryonic stem cells (hESCs and human fibroblasts (hFibs revealed that haGSCs showed a characteristic germ- and pluripotency-associated gene expression profile with some similarities to hESCs and with a significant distinction from somatic hFibs. Genome-wide comparisons with microarray analysis confirmed that different haGSC colonies exhibited gene expression heterogeneity with more or less pluripotency. The results of this study confirm that haGSCs are adult stem cells with a specific molecular gene expression profile in vitro, related but not identical to true pluripotent stem cells. Under ES-cell conditions haGSC colonies could be selected and maintained in a partial pluripotent state at the molecular level, which may be related to their cell plasticity and potential to differentiate into cells of all germ layers.

  15. Mixed malignant germ cell tumor of ovary

    Directory of Open Access Journals (Sweden)

    Sviračević Branko

    2011-01-01

    Full Text Available Introduction. Malignant tumours of ovary germ epithelium are very rare and account for about 2-5% of all ovarian tumours of germ origin. In adolescent patients under 20 years of age diagnosed to have ovarian tumour, these tumours originate from germ cells in about 70% of cases. Depending on the stage of the disease, medical treatment and age, the death rate ranges from 25% to 84%. A special group of germ tumours are mixed germ cells tumours built of two or more different types of germ tumours. Case report. This paper gives a diagnostic-therapeutic procedure and the clinical picture with the course and outcome of the decease in a nineteen-year old patient with a mixed malignant germ tumour (dysgerminoma, choriocarcinoma, immature teratoma found in one of the ovaries. It also deals with the appearance and development, some characteristics and histological build of the tumours diagnosed in this case. Conclusion. Malignant tumours of ovary germ epithelium are very rare and develop in female population under 30 years of age. They are characterized by a high degree of malignity. They are resistant to cytostatic treatment, they spread very quickly with the lethal outcome. The course of the disease is not characteristic and is usually masked under some other acute gynaecological disease. The definitive diagnosis is made after laparotomy and pathohistological analysis of the tumour tissue.

  16. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2016-07-26

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  17. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts

    DEFF Research Database (Denmark)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini;

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome pr...

  18. Germ cell cancer and disorders of spermatogenesis

    DEFF Research Database (Denmark)

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

    1998-01-01

    in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which...... is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated......Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads...

  19. In vitro reconstitution of germ cell development

    Institute of Scientific and Technical Information of China (English)

    Yun Li

    2011-01-01

    Mammalian germ line cells undergo unique cellular and genetic changes under the regulation of specific regulators,in different stages as they develop and differentiate into functional gametes.It is a fundamental challenge to reconstitute gametes development in vitro,because of the complexity of the regulation process.In mice,embryonic stem cells (ESCs) develop into Epiblast stem cells at around embryonic day 6.0 (E6.0) induced by the bone morphogenetic protein 4 (Bmp4) (Lawson et al.,1999).At around E7.25,epiblast stem cells develop into primordial germ cells (PGCs)in the extraembryonic mesoderm regulated by the critical transcriptional regulator Blimp1(Prdm1) and Prdm14 (Yamaji et al.,2008).PGCs are the origins for the oocytes and the spermatozoa (a motile sperm cell).

  20. MRI of intracranial germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sumida, M. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Uozumi, T. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kiya, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Mukada, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Arita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Kurisu, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Sugiyama, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Onda, J. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Satoh, H. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Ikawa, F. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan); Migita, K. [Dept. of Neurosurgery, Hiroshima Univ. School of Medicine, Hiroshima (Japan)

    1995-01-01

    We reviewed MRI findings in proven intracranial germ cell tumours in 22 cases, 12 of whom received Gd-DTPA. On T1-weighted images, the signal intensity of the tumour parenchyma was moderately low in 19 cases and isointense in 3; on T2-weighted images, it was high in all cases. Regions of different intensity thought to be cysts were found in 17 (77 %): 7 of 12 patients with germinoma (58 %) and in all other cases. Of the 13 patients with pineal lesions T1-weighted sagittal images showed the aqueduct to be obstructed in 5, stenotic in 7 and normal in 1. Strong contrast enhancement was observed in all 12 cases. Of the 14 patients with suprasellar lesions, 5 were found to have an intrasellar extension, and in 3 of these, the normal pituitary gland, which could be distinguished from the tumour, was displaced anteriorly. Ten patients (45 %) had multiple lesions. (orig.)

  1. MR imaging of intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Masayuki; Takashima, Tsutomu; Akakura, Yukari (Kanazawa Univ. (Japan). School of Medicine) (and others)

    1994-04-01

    MRI of 13 patients with intracranial germ cell tumor (GCT) was performed with a 1.5 T superconductive scanner. T1-and T2-weighted images (T1WI and T2WI) and Gd-DTPA-enhanced T1-weighted images (Gd-T1WI) were obtained. On T1WI and T2WI, five germinomas and one teratoma were homogeneously isointense with gray matter. Two germinomas with cystic component exhibited markedly hypointense and hyperintense areas, respectively. Three teratomas were heterogeneous on both sequences due to cystic portion, fat, and hemorrhage. Yolk sac tumor (YST) was isointense on T1WI and heterogeneous on T2WI. On Gd-T1WI, five germinomas and YST were homogeneously enhanced. All but one of the others were heterogeneously enhanced. There were increased AFP in YST and increased HCG in malignant teratoma. Differential diagnosis of GCT may be possible with MRI. However, tumor markers should be taken into consideration. (author).

  2. Radiation therapy for intracranial germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Shingo; Hayakawa, Kazushige; Tsuchiya, Miwako; Arai, Masahiko; Kazumoto, Tomoko; Niibe, Hideo; Tamura, Masaru

    1988-04-01

    The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1 % for germinomas and 38.1 % for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis iradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.

  3. Progress in gene transfer by germ cells in mammals

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Use of germ cells as vectors for transgenesis in mammals has been well developed and offers exciting prospects for experimental and applied biology, agricultural and medical sciences.Such approach is referred to as either male germ cell mediated gene transfer (MGCMGT)or female germ cell mediated gene transfer(FGCMGT)technique.Sperm-mediated gene transfer (SMGT),including its alternative method,testis-mediated gene transfer(TMGT),becomes an established and reliable method for transgenesis.They have been extensively used for producing transgenic animals.The newly developed approach of FGCMGT,ovary-mediated gene transfer(OMGT) is also a novel and useful tool for efficient transgenesis.This review highlights an overview of the recent progress in germ cell mediated gene transfer techniques,methods developed and mechanisms of nucleic acid uptake by germ cells.

  4. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    Directory of Open Access Journals (Sweden)

    Aaraby Yoheswaran Nielsen

    2016-06-01

    Full Text Available Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

  5. Testicular germ cell tumours and parental occupational exposure to pesticides

    DEFF Research Database (Denmark)

    Le Cornet, Charlotte; Fervers, Béatrice; Oksbjerg Dalton, Susanne;

    2015-01-01

    OBJECTIVES: A potential impact of exposure to endocrine disruptors, including pesticides, during intrauterine life, has been hypothesised in testicular germ cell tumour (TGCT) aetiology, but exposure assessment is challenging. This large-scale registry-based case-control study aimed to investigate...... controls per case were randomly selected from the general national populations, matched on year of birth. Information on parental occupation was collected through censuses or Pension Fund information and converted into a pesticide exposure index based on the Finnish National Job-Exposure Matrix. RESULTS......: A total of 9569 cases and 32 028 controls were included. No overall associations were found for either maternal or paternal exposures and TGCT risk in their sons, with ORs of 0.83 (95% CI 0.56 to 1.23) and of 1.03 (0.92 to 1.14), respectively. Country-specific estimates and stratification by birth cohorts...

  6. Spermatogonial Nature of the Germ Cell Component of Canine Testicular Mixed Germ Cell-Sex Cord Stromal Tumours.

    Science.gov (United States)

    Mizukami, S; Murakami, T; Tanaka, T; Machida, N; Nomura, K; Yoshida, T; Shibutani, M

    2016-07-01

    The present study has characterized the germ cell component of canine testicular mixed germ cell-sex cord stromal tumours (MGSCTs) by examining the histological nature and histochemical and immunohistochemical features using gonocytic and spermatogonial cellular markers, c-Kit, placental alkaline phosphatase (PLAP), protein gene product 9.5 (PGP9.5), Sal-like protein 4 (SALL4), and the periodic acid-Schiff (PAS) reaction. Histologically, all 45 examples of MGSCTs were classified as spermatocytic seminomas (SSs) and Sertoli cell tumours in combination. The germ cell component of all MGSCTs was negative by PAS staining. Immunohistochemically, PLAP immunoreactivity was lacking in the germ cell component of all MGSCTs, which is not consistent with a gonocytic origin. The germ cell component was positive for PGP9.5 and SALL4 in all MGSCTs and positive for c-Kit in 53% of MGSCTs, which is consistent with the phenotype of spermatogonia. Furthermore, the germ cell component in 71% of MGSCTs had moderate immunoreactivity for SALL4, which is suggestive of a spermatogonial phenotype. Conversely, 29% of cases had a minor population of germ cells showing strong SALL4 immunoreactivity, suggesting a phenotype similar to prespermatogonia. The results suggest that the germ cell component of canine MGSCTs is morphologically classified as SS, with the majority of cases showing the spermatogonial phenotype and some cases containing a small population of prespermatogonia. PMID:27241073

  7. Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index

    Institute of Scientific and Technical Information of China (English)

    Li ZENG; Xiang-Tian KONG; Jin-Wei SU; Tong-Li XIA; Yan-Qun NA; Ying-Lu GUO

    2001-01-01

    To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. Methods: Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. Results: The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis ( 14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar Pis (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. Conclusion: PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.

  8. Laparotomy for post chemotherapy residue in ovarian germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mathew G

    2006-01-01

    Full Text Available Background : Primary conservative surgery and cisplatin-based chemotherapy have resulted in high cure ratesin malignant ovarian germ cell tumors. A significant proportion of advanced tumors may have post-chemotherapyresidue and it is important to distinguish necrosis or fibrosis without viable tumor from persistent viable tumorand teratoma. Aims : To evaluate the role of laparotomy in assessing the nature of post-chemotherapy residue in ovariangerm cell tumors. Materials and Methods : Eighty-three patients with malignant ovarian germ cell tumors seen at Cancer Institute,Chennai between 1992 and 2002 were studied. Sixty-eight patients completed combination chemotherapywith cisplatin regimes, of whom 35 had radiological residual masses. Twenty-nine out of these 35 patientsunderwent laparotomy to assess the nature of the residue. Results : On laparotomy, three patients had viable tumor, seven immature teratoma, three mature teratomaand 16 only necrosis or fibrosis. None of our patients with dysgerminoma, embryonal carcinoma, absence ofteratoma element in the primary tumor and radiological residue of < 5 cm had viable tumor whereas all patientswith tumors containing teratoma component initially had residual tumor. Absence of viable disease was higherin patients who had normalization of serum markers by two cycles of chemotherapy. Conclusion : Our study suggests that patients with absence of teratoma element initially, radiological residue of< 5 cm and normalization of serum markers after two cycles of chemotherapy do not require surgery to assessthe nature of post-chemotherapy residue. However, laparotomy should be performed in patients with tumorsthat initially contain teratoma element and in those with sluggish tumor marker response after two cycles ofchemotherapy since they have a high chance of having viable postchemotherapy residue.

  9. Enhancement of germ cell apoptosis induced by ethanol in transgenic mice overexpressing Fas Ligand

    Institute of Scientific and Technical Information of China (English)

    HENG CHUAN XIA; FENG LI; ZHEN LI; ZU CHUAN ZHANG

    2003-01-01

    It was suggested that chronic ethanol exposure could result in testicular germ cell apoptosis, but the mechanism is still unclear. In the present study, we use a model of transgenic mice ubiquitously overexpressing human FasL to investigate whether Fas ligand plays a role in ethanol-induced testicular germ cell apoptosis. Both wild-type (WT)mice and transgenic (TG) mice were treated with acute ethanol (20% v/v) by introperitoneal injection for five times.After ethanol injection, WT mice displayed up-regulation of Fas ligand in the testes, which was shown by FITCconjugated flow cytometry and western blotting. Moreover, TG mice exhibited significantly more apoptotic germ cells than WT mice did after ethanol injection, which was demonstrated by DNA fragmentation, PI staining flow cytometry and TUNEL staining. In addition, histopathological examination revealed that degenerative changes of epithelial component of the tubules occurred in FasL overexpressing transgenic mice while testicular morphology was normal in wild-type mice after acute ethanol exposure, suggesting FasL expression determines the sensitivity of testes to ethanol in mice. In summary, we provide the direct evidences that Fas ligand mediates the apoptosis of testicular germ cells induced by acute ethanol using FasL transgenic mice.

  10. Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2015-05-11

    Recurrent Extragonadal Seminoma; Recurrent Malignant Extragonadal Germ Cell Tumor; Recurrent Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Testicular Cancer; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

  11. MRI of intracranial germ-cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Liang, L.; Korogi, Y.; Sugahara, T.; Ikushima, I.; Shigematsu, Y.; Okuda, T.; Takahashi, M. [Department of Radiology, Kumamoto University School of Medicine (Japan); Kochi, M.; Ushio, Y. [Department of Neurosurgery, Kumamoto University School of Medicine (Japan)

    2002-05-01

    Abstract. Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes. (orig.)

  12. Effects of 60 Hz electromagnetic field exposure on testicular germ cell apoptosis in mice

    Institute of Scientific and Technical Information of China (English)

    JinSangLee; SangSeokAhn; KyeongCheonJung; Yoon-WonKim; SangKonLee

    2004-01-01

    Aim:To evaluate the effects of 60 Hz extremely low frequency (ELF) elelctromagnetic field (EMF) exposure on germ cell apoptosis in the testis of mice.Methods:Adult male BALB/c mice (7 weeks of age) were exposed to a 60 Hz EMF of 0.1 mT or 0.5 mT for 24 h/day.A sham-exposed group served as the control.After 8 weeks of exposure,the mice were sacrificed.Germ cell apoptosis in the testis was assessed by histopathological examination,the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) and flow cytometric examination of isolated spermatogenic cells stained with 7 aminoactinomycin D (7-AAD).Results:EMF exposure did not significantly affect the body and testis weights,but significantly increased the incidence of germ cell death.The distinguishing morphological feature of EMF exposure was a decrement in the number of well organized seminiferous tubules.Quantitative analysis of TUNEL-positive germ cells showed a significantly higher apoptotic rate in the 0.5 mT exposed mice than that in the sham controls (P<0.05),while the difference between the two exposed groups was insignificant.The TUNEL-positive cells were mainly spermatogonia.In flow cytometryanalysis,the percentage of live cells [forward scatter count (FSC)hgh7-AAD-] was lower in the exposed groups than that in the controls (Figure 5A),but the decrease in viability was not statistically significant.Conclusion:Continuousexposure to ELF EMF may induce testicular germ cell apoptosis in mice.(Asian J Androl 2004 Mar;6:29-34)

  13. General Information About Childhood Central Nervous System Germ Cell Tumors

    Science.gov (United States)

    ... germ cell tumors to form is near the pineal gland and in an area of the brain that ... of the inside of the brain, showing the pineal and pituitary glands, optic nerve, ventricles (with cerebrospinal fluid shown in ...

  14. Treatment Options for Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  15. General Information about Childhood Extracranial Germ Cell Tumors

    Science.gov (United States)

    ... immature teratomas , and malignant germ cell tumors: Mature Teratomas Mature teratomas are the most common type of ... that cause signs and symptoms of disease. Immature Teratomas Immature teratomas also usually occur in the sacrum ...

  16. Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

    OpenAIRE

    Aaraby Yoheswaran Nielsen; Morten Frier Gjerstorff

    2016-01-01

    Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the ...

  17. Germ cell transplantation and testis tissue xenografting in mice.

    Science.gov (United States)

    Tang, Lin; Rodriguez-Sosa, Jose Rafael; Dobrinski, Ina

    2012-01-01

    Germ cell transplantation was developed by Dr. Ralph Brinster and colleagues at the University of Pennsylvania in 1994(1,2). These ground-breaking studies showed that microinjection of germ cells from fertile donor mice into the seminiferous tubules of infertile recipient mice results in donor-derived spermatogenesis and sperm production by the recipient animal(2). The use of donor males carrying the bacterial β-galactosidase gene allowed identification of donor-derived spermatogenesis and transmission of the donor haplotype to the offspring by recipient animals(1). Surprisingly, after transplantation into the lumen of the seminiferous tubules, transplanted germ cells were able to move from the luminal compartment to the basement membrane where spermatogonia are located(3). It is generally accepted that only SSCs are able to colonize the niche and re-establish spermatogenesis in the recipient testis. Therefore, germ cell transplantation provides a functional approach to study the stem cell niche in the testis and to characterize putative spermatogonial stem cells. To date, germ cell transplantation is used to elucidate basic stem cell biology, to produce transgenic animals through genetic manipulation of germ cells prior to transplantation(4,5), to study Sertoli cell-germ cell interaction(6,7), SSC homing and colonization(3,8), as well as SSC self-renewal and differentiation(9,10). Germ cell transplantation is also feasible in large species(11). In these, the main applications are preservation of fertility, dissemination of elite genetics in animal populations, and generation of transgenic animals as the study of spermatogenesis and SSC biology with this technique is logistically more difficult and expensive than in rodents. Transplantation of germ cells from large species into the seminiferous tubules of mice results in colonization of donor cells and spermatogonial expansion, but not in their full differentiation presumably due to incompatibility of the

  18. Pediatric Germ Cell Tumors; A 10-year Experience

    OpenAIRE

    Khaleghnejad-tabari, Ahmad; Mirshemirani, Alireza; Rouzrokh, Mohsen; Mohajerzadeh, Leily; Khaleghnejad-Tabari, Nasibeh; Hasas-Yeganeh, Shaghayegh

    2014-01-01

    Objective: The aim of this study was to evaluate the outcome of germ cell tumors in patients admitted to our center during a ten year period. Methods: In a retrospective descriptive study, patients with the pathological diagnosis of germ cell tumor (GCT) were included. All records were evaluated and patients followed by personal visit in clinic or phone call. Data regarding age, sex, tumor site, bio-chemical assay, pathology, treatment and outcomes were gathered. For qualitative variables we ...

  19. The chemosensitivity of testicular germ cell tumors.

    Science.gov (United States)

    Voutsadakis, Ioannis A

    2014-04-01

    Although rare cancers overall, testicular germ cell tumors (TGCTs) are the most common type of cancer in young males below 40 years of age. Both subtypes of TGCTs, i.e., seminomas and non-seminomas, are highly curable and the majority of even metastatic patients may expect to be cured. These high cure rates are not due to the indolent nature of these cancers, but rather to their sensitivity to chemotherapy (and for seminomas to radiotherapy). The delineation of the cause of chemosensitivity at the molecular level is of paramount importance, because it may provide insights into the minority of TGCTs that are chemo-resistant and, thereby, provide opportunities for specific therapeutic interventions aimed at reverting them to chemosensitivity. In addition, delineation of the molecular basis of TGCT chemo-sensitivity may be informative for the cause of chemo-resistance of other more common types of cancer and, thus, may create new therapeutic leads. p53, a frequently mutated tumor suppressor in cancers in general, is not mutated in TGCTs, a fact that has implications for their chemo-sensitivity. Oct4, an embryonic transcription factor, is uniformly expressed in the seminoma and embryonic carcinoma components of non-seminomas, and its interplay with p53 may be important in the chemotherapy response of these tumors. This interplay, together with other features of TGCTs such as the gain of genetic material from the short arm of chromosome 12 and the association with disorders of testicular development, will be discussed in this paper and integrated in a unifying hypothesis that may explain their chemo-sensitivity. PMID:24692098

  20. Germ Cell Neoplasia In Situ (GCNIS). Evolution of the Current Nomenclature for Testicular Pre-invasive Germ Cell Malignancy

    DEFF Research Database (Denmark)

    Berney, D M; Looijenga, Lhj; Idrees, M;

    2016-01-01

    , and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'Intra-tubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intra-epithelial neoplasia' (TIN). We wish here, to review the history of discovery and controversy on these names, and introduce...... the reasoning for uniting behind a new name, endorsed unanimously at the WHO consensus classification 2016: Germ cell neoplasia in situ (GCNIS). This article is protected by copyright. All rights reserved....

  1. Six cases of malignant germ-cell tumors (grade 4). Comparison with germinoma (grade 2, 3) on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, M.; Machida, T.; Maehara, T. (Tokyo Univ. (Japan). Faculty of Medicine)

    1981-08-01

    The CT patterns of six malignant germ-cell tumors other than germinomas (one embryonal carcinoma, one choriocarcinoma, one yolk sac tumor, and three immature teratomas) were compared with those of 12 germinomas (ten suprasellar, one pineal, and one basal ganglia). The effects of irradiation and the changes in the concentration of serum ..cap alpha..-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were compared by means of serial studies. 1. Pre-contrast CT Four of the six (67%) malignant germ-cell tumors showed isodense masses with irregular margins that contained calcified dots and small necrotic cavities. All 12 germinomas showed round, high-density masses with smooth margins without necrotic cavities. The suprasellar germinomas showed no calcification on CT. 2. Post-contrast CT Both malignant germ-cell tumors and germinomas showed a strong enhancement after contrast administration. 3. Change in size after irradiation Malignant germ-cell tumors did not show a decrease in size after radiotherapy (20 - 40 Gy), although the necrotic cavities enlarged in three out of four tumors. Germinomas were highly radiosensitive and showed a remarkable change in size on follow-up CT after irradiation. 4. Serum AFP and HCG The concentrations of serum AFP and/or HCG before therapy were abnormally high in five malignant germ-cell tumors. In three out of four patients, the concentration of serum AFP was normalized, but in one patient the concentration of AFP increased even after irradiation.

  2. Alleviative effect of quercetin on germ cells intoxicated by 3-methyl-4-nitrophenol from diesel exhaust particles

    Institute of Scientific and Technical Information of China (English)

    Tong-liang BU; Yu-dong JIA; Yu-ling MI; Jin-xing LIN; Cai-qiao ZHANG

    2012-01-01

    As a component of diesel exhaust particles,3-methyl-4-nitrophenol (4-nitro-m-cresol,PNMC) is also a metabolite of the insecticide fenitrothion and imposes hazardous effects on human health.In the present study,the alleviative effect of a common antioxidant fiavonoid quercetin on mouse germ cells intoxicated by PNMC was investigated.Results showed that a single intraperitoneal injection of PNMC at 100 mg/kg induced severe testicular damage after one week.PNMC-treated mice showed a significant loss of germ cells (approximate 40% loss of round germ cells).PNMC caused an increase of hydroxyl radical and hydrogen peroxide production and lipid peroxidation,as well as a decrease in glutathione level,superoxide dismutase and glutathione peroxidase activities.Furthermore,treatment of PNMC increased expression of the pro-apoptotic protein Bax and decreased expression of the anti-apoptotic protein Bcl-XL in germ cells.In addition,testicular caspase-3 activity was significantly up-regulated and germ cell apoptosis was significantly increased in the PNMC-treated mice.In contrast,combined administration of quercetin at 75 mg/kg significantly attenuated PNMC-induced testicular toxicity.These results indicate that the antioxidant quercetin displays a remarkable protective effect on PNMC-induced oxidative damage in mouse testes and may represent an efficient supplement to attenuate reproductive toxicity by environmental toxicants to ensure healthy sperm production.

  3. Urethral metastasis from non-seminomatous germ cell tumor: a case report

    OpenAIRE

    Joffe Johnathan; Chilka Sameer; Wah Tze; Agarwal Vijay; Stark Dan

    2011-01-01

    Abstract Introduction We present a case of nonseminomatous germ cell tumor of the testes with acute urinary retention secondary to urethral metastasis. This presentation, and similar cases of urethral metastasis from this tumor, have not been reported previously. Case presentation A 35-year-old Caucasian man presented to hospital with a history of acute urinary retention. On examination he was found to have right testicular enlargement with raised β-human chorionic gonadotrophin, serum α-feto...

  4. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    OpenAIRE

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Vera M. Abeler; Rajpert-De Meyts, Ewa; Ragnhild A Lothe

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their...

  5. Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Nielsen, John E; Almstrup, Kristian;

    2004-01-01

    and protein level in normal human tissues and a panel of tumors and tumor-derived cell lines. In the gonads, we established the ontogeny of expression of AP-2gamma in normal and dysgenetic samples. We also investigated the regulation of AP-2gamma by steroids and retinoic acid. RESULTS: We detected abundant AP......-2gamma in testicular CIS and in testicular germ cell tumors of young adults and confirmed differential expression of AP-2gamma in somatic tumors. We found that AP-2gamma expression was regulated by retinoic acid in an embryonal carcinoma cell line (NT2). The investigation of ontogeny of AP-2gamma....... CONCLUSIONS: AP-2gamma is developmentally regulated and associated with the undifferentiated phenotype in germ cells. This transcription factor may be involved in self-renewal and survival of immature germ cells and tissue-specific stem cells. AP-2gamma is a novel marker of testicular CIS and CIS...

  6. Follistatin288 Regulates Germ Cell Cyst Breakdown and Primordial Follicle Assembly in the Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Zhengpin Wang

    Full Text Available In mammals, the primordial follicle pool represents the entire reproductive potential of a female. The transforming growth factor-β (TGF-β family member activin (ACT contributes to folliculogenesis, although the exact mechanism is not known. The role of FST288, the strongest ACT-neutralizing isoform of follistatin (FST, during cyst breakdown and primordial follicle formation in the fetal mice ovary was assessed using an in vitro culture system. FST was continuously expressed in the oocytes as well as the cuboidal granulosa cells of growing follicles in perinatal mouse ovaries. Treatment with FST288 delayed germ cell nest breakdown, particularly near the periphery of the ovary, and dramatically decreased the percentage of primordial follicles. In addition, there was a dramatic decrease in proliferation of granulosa cells and somatic cell expression of Notch signaling was impaired. In conclusion, FST288 impacts germ cell nest breakdown and primordial follicle assembly by inhibiting somatic cell proliferation.

  7. Extremely Low Frequency Magnetic Fields Induce Spermatogenic Germ Cell Apoptosis: Possible Mechanism

    Directory of Open Access Journals (Sweden)

    Sang-Kon Lee

    2014-01-01

    Full Text Available The energy generated by an extremely low frequency electromagnetic field (ELF-EMF is too weak to directly induce genotoxicity. However, it is reported that an extremely low frequency magnetic field (ELF-MF is related to DNA strand breakage and apoptosis. The testes that conduct spermatogenesis through a dynamic cellular process involving meiosis and mitosis seem vulnerable to external stress such as heat, MF exposure, and chemical or physical agents. Nevertheless the results regarding adverse effects of ELF-EMF on human or animal reproductive functions are inconclusive. According to the guideline of the International Commission on Non-Ionizing Radiation Protection (ICNIRP; 2010 for limiting exposure to time-varying MF (1 Hz to 100 kHz, overall conclusion of epidemiologic studies has not consistently shown an association between human adverse reproductive outcomes and maternal or paternal exposure to low frequency fields. In animal studies there is no compelling evidence of causal relationship between prenatal development and ELF-MF exposure. However there is increasing evidence that EL-EMF exposure is involved with germ cell apoptosis in testes. Biophysical mechanism by which ELF-MF induces germ cell apoptosis has not been established. This review proposes the possible mechanism of germ cell apoptosis in testes induced by ELF-MF.

  8. Establishment and applications of male germ cell and Sertoli cell lines.

    Science.gov (United States)

    Wang, Hong; Wen, Liping; Yuan, Qingqing; Sun, Min; Niu, Minghui; He, Zuping

    2016-08-01

    Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and Sertoli cells can have significant applications in treating male infertility and other diseases. However, primary male germ cells are hard to proliferate in vitro and the number of spermatogonial stem cells is scarce. Therefore, methods that promote the expansion of these cell populations are essential for their use from the bench to the bed side. Notably, a number of cell lines for rodent spermatogonia, spermatocytes and Sertoli cells have been developed, and significantly we have successfully established a human spermatogonial stem cell line with an unlimited proliferation potential and no tumor formation. This newly developed cell line could provide an abundant source of cells for uncovering molecular mechanisms underlying human spermatogenesis and for their utilization in the field of reproductive and regenerative medicine. In this review, we discuss the methods for establishing spermatogonial, spermatocyte and Sertoli cell lines using various kinds of approaches, including spontaneity, transgenic animals with oncogenes, simian virus 40 (SV40) large T antigen, the gene coding for a temperature-sensitive mutant of p53, telomerase reverse gene (Tert), and the specific promoter-based selection strategy. We further highlight the essential applications of these cell lines in basic research and translation medicine. PMID:27069011

  9. NANOG priming before full reprogramming may generate germ cell tumours

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    I Grad

    2011-11-01

    Full Text Available Reprogramming somatic cells into a pluripotent state brings patient-tailored, ethical controversy-free cellular therapy closer to reality. However, stem cells and cancer cells share many common characteristics; therefore, it is crucial to be able to discriminate between them. We generated two induced pluripotent stem cell (iPSC lines, with NANOG pre-transduction followed by OCT3/4, SOX2, and LIN28 overexpression. One of the cell lines, CHiPS W, showed normal pluripotent stem cell characteristics, while the other, CHiPS A, though expressing pluripotency markers, failed to differentiate and gave rise to germ cell-like tumours in vivo. Comparative genomic hybridisation analysis of the generated iPS lines revealed that they were genetically more stable than human embryonic stem cell counterparts. This analysis proved to be predictive for the differentiation potential of analysed cells. Moreover, the CHiPS A line expressed a lower ratio of p53/p21 when compared to CHiPS W. NANOG pre-induction followed by OCT3/4, SOX2, MYC, and KLF4 induction resulted in the same tumour-inducing phenotype. These results underline the importance of a re-examination of the role of NANOG during reprogramming. Moreover, this reprogramming method may provide insights into primordial cell tumour formation and cancer stem cell transformation.

  10. Tumour markers in germ cell tumours and thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mann, K.

    1988-02-01

    In patients with germ cell tumours of gonadal and extragonadal origin both markers, human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) are madatory for diagnosis and control of treatment. In seminoma, we found preoperatively elevated levels of hCG(+hCG-..beta..) in 42/349 patients (12%) up to 1200 mlU/ml using a polyclonal radioimmunoassay (1. IRP hCG standard 75/537). Lactatedehydrogenase can be useful in marker negative patients. Serum levels reflect tumour burden even if not highly specific. Presently, placental alkaline phosphatase is under discussion for seminoma. However, commercial kits are not available. As a relatively high secretion of hCG/..beta../hCG was found in gestational trophoblastic diseases, this parameters may be useful for differential diagnosis in pregnancy. In the follow-up of patients with differentiated thyroid carcinoma the determination of thyroglobulin (Tg) in combination with ultrasound of the thyroid and X-ray of the chest is sufficient. For Tg-determination thyroid hormone replacement therapy must be discontinued only in rare single cases with borderline levels, which need radioiodtesting additionally. Calcitonin is the most important marker in medullary thyroid carcinoma. Pentagastrin stimulated calcitonin as screening test is necessary, if multiple endocrine adenomatosis or the familial forms are suspected. In single cases benefit came from new scintigraphic methods such as /sup 131/I-metaiodo-benzylguanidine or /sup 201/thallium-chloride.

  11. Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration

    Science.gov (United States)

    Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul

    2016-01-01

    We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour.

  12. "Mixed germ cell testicular tumor" in an adult female

    Directory of Open Access Journals (Sweden)

    Udasimath Shivakumarswamy

    2012-01-01

    Full Text Available The androgen insensitivity (testicular feminization syndrome was described by Morris in phenotypic females with 46XY karyotype, presenting with primary amenorrhea, adequate breast development, and absent or scanty pubic or axillary hair. Gonads consist usually of seminiferous tubules without spermatogenesis. These patients have a 5-10% risk of developing germ cell tumors, usually after the complete development of secondary female sexual characteristics. We hereby report a case considered as a female with married life of 15 years, who was operated for severe abdominal pain. Phenotype characters were that of female. Microscopic examination of the tumor from the abdomen revealed germinoma and yolk sac tumor with adjacent seminiferous tubules. Karyotyping showed 46XY. Final diagnosis of malignant mixed germ cell tumor in androgen insensitivity syndrome was made. Surveillance may be the most appropriate option when these conditions are initially diagnosed in adulthood to prevent development of germ cell tumors.

  13. Metachronous bilateral testicular germ cell tumors: Report of two cases

    Directory of Open Access Journals (Sweden)

    James Francis

    2009-01-01

    Full Text Available Metachronous bilateral testicular germ cell tumors is a rare known problem. However, no report of metachronus bilateralism was identified in the PubMed database published from India so far, where testicular cancer is relatively rare. We report the cases of two gentlemen. One had stage 1 nonseminomatous germ cell tumor (NSGCT at the age of 32 in 1990 and developed marker relapse on surveillance and had chemotherapy using cisplatin and etoposide for four cycles. He developed contralateral seminoma in the testis 13 years later. Another patient had left orchidectomy in 2003 for NSGCT, had adjuvant BEP for two cycles, and developed a contralateral testicular tumor 5 years later, which was also seminoma. As more patients with germ cell tumors are cured with chemotherapy, long-term problems become important. Contralateral testicular tumor is one of them. As it can be very late, many years of continued follow-up examination and patients′ awareness are necessary.

  14. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    Science.gov (United States)

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease. PMID:26548627

  15. Boule is present in fish and bisexually expressed in adult and embryonic germ cells of medaka.

    Directory of Open Access Journals (Sweden)

    Hongyan Xu

    Full Text Available BACKGROUND: The DAZ family genes boule, daz and dazl encode RNA binding proteins essential for fertility of diverse animals including human. dazl has bisexual expression in both mitotic and meiotic germ cells, whereas daz has male premeiotic expression, and boule is largely a unisexual meiotic regulator. Although boule has been proposed as the ancestor for dazl/daz by gene duplication, it has been identified only in invertebrates and mammals. It has, however, remained unclear when and how the DAZ family has evolved in vertebrates. METHODOLOGY AND PRINCIPAL FINDINGS: This study was aimed at identifying and characterizing the DAZ family genes in fish as the basal vertebrate. We show that boule and dazl coexist in medaka and stickleback. Similar to the medaka dazl (Odazl, the medaka boule (Obol is maternally supplied and segregates with primordial germ cells. Surprisingly, Obol is expressed in adult germ cells at pre-meiotic and meiotic stages of spermatogenesis and oogenesis. However, the maximal meiotic Obol expression in spermatocytes contrasts with the predominant pre-meiotic Odazl expression in spermatogonia, and the diffuse cytoplasmic Obol distribution in early oocytes contrasts with the Odazl concentration in the Balbinani's body. CONCLUSIONS: The identification of fish boule and dazl genes provides direct evidence for the early gene duplication during vertebrate evolution. Our finding that Obol exhibits bisexual expression in both embryonic and adult germ cells considerably extends the diversity of boule expression patterns and offers a new insight into the evolutions of DAZ family members, expression patterns and functions in animal fertility.

  16. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    Science.gov (United States)

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  17. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.

    Science.gov (United States)

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Abeler, Vera M; Rajpert-De Meyts, Ewa; Lothe, Ragnhild A

    2013-06-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  18. Germ cell sex prior to meiosis in the rainbow trout

    OpenAIRE

    Li, Mingyou; Shen, Qian; Wong, Foong Mei; Xu, Hongyan; Hong, Ni; Zeng, Lingbing; Liu, Lin; Wei, Qiwei; Hong, Yunhan

    2011-01-01

    Germ cells make two major decisions when they move from an indeterminate state to their final stage of gamete production. One decision is sexual commitment for sperm or egg production, and the other is to maintain mitotic division or entry into meiosis. It is unclear whether the two decisions are made as a single event or separate events, because there has been no evidence for the presence of germ cell sex prior to meiosis. Here we report direct evidence in the fish rainbow trout that gonia h...

  19. Early imaging findings in germ cell tumors arising from the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Mi [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Kyungpook National University Medical Center, Department of Radiology, Daegu (Korea, Republic of); Kim, In-One; Choi, Young Hun; Cheon, Jung-Eun; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology and Institute of Radiation Medicine, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Cho, Hyun-Hae [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Ewha Woman' s University Mokdong Hospital, Department of Radiology, Seoul (Korea, Republic of); You, Sun Kyoung [Seoul National University College of Medicine, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Chungnam National University Hospital, Department of Radiology, Daejeon (Korea, Republic of)

    2016-05-15

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  20. Early imaging findings in germ cell tumors arising from the basal ganglia

    International Nuclear Information System (INIS)

    It is difficult to diagnosis early stage germ cell tumors originating in the basal ganglia, but early recognition is important for better outcome. To evaluate serial MR images of basal ganglia germ cell tumors, with emphasis on the features of early stage tumors. We retrospectively reviewed serial MR images of 15 tumors in 14 children and young adults. We categorized MR images of the tumors as follows: type I, ill-defined patchy lesions (<3 cm) without cyst; type II, small mass lesions (<3 cm) with cyst; and type III, large lesions (≥3 cm) with cyst. We also assessed temporal changes of the MR images. On the initial images, 8 of 11 (73%) type I tumors progressed to types II or III, and 3 of 4 (75%) type II tumors progressed to type III. The remaining 4 tumors did not change in type. All type II tumors (5/5, 100%) that changed from type I had a few tiny cysts. Intratumoral hemorrhage was observed even in the type I tumor. Ipsilateral hemiatrophy was observed in most of the tumors (13/15, 87%) on initial MR images. As tumors grew, cystic changes, intratumoral hemorrhage, and ipsilateral hemiatrophy became more apparent. Early stage basal ganglia germ cell tumors appear as ill-defined small patchy hyperintense lesions without cysts on T2-weighted images, are frequently associated with ipsilateral hemiatrophy, and sometimes show microhemorrhage. Tumors develop tiny cysts at a relatively early stage. (orig.)

  1. Effects of losartan on experimental varicocele-induced testicular germ cell apoptosis.

    Science.gov (United States)

    Bolat, D; Oltulu, F; Uysal, A; Kose, T; Gunlusoy, B; Yigitturk, G; Turk, N S; Turan, T

    2016-09-01

    To investigate the potential protective effects of losartan on varicocele-induced germ cell apoptosis, 24 adult male Sprague Dawley rats were divided into three groups: a sham operation was performed in SHAM group, and experimental left varicocele was created in VAR and VAR + LOS groups. Additionally, in VAR + LOS group, losartan was administered for 30 days starting on the day of surgery. At the end of 30 days, all animals were sacrificed and left orchiectomy was performed. Testicular injury and spermatogenesis were evaluated according to Johnsen scoring system. To assess the nitrosative stress, immunohistochemical staining for endothelial nitric oxide synthase was used and evaluated by H-score and apoptotic index (AI) of germ cells was analysed by TUNEL method. A significant decrease in the mean Johnsen score (JS) was observed in VAR group compared with SHAM (p AI were significantly higher in VAR group compared with SHAM (p AI were significantly decreased compared with VAR group (p < .001 and .01, respectively). Findings of this suggest that losartan acts as a potent protective agent against varicocele-induced germ cell apoptosis. PMID:27373273

  2. Hormonal treatment may harm the germ cells in 1 to 3-year-old boys with cryptorchidism

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Visfeldt, J

    2000-01-01

    Hormonal treatment with human chorionic gonadotropin (HCG) or gonadotropin releasing hormone may be given initially for cryptorchidism. We evaluated whether hormonal treatment is safe for the germ cells in boys with cryptorchidism 1 to 3 years old in whom follicle-stimulating hormone, luteinizing...

  3. Generation of male germ cells from induced pluripotent stem cells (iPS cells): an in vitro and in vivo study

    Institute of Scientific and Technical Information of China (English)

    Yong Zhu; Xi-Zhi Guo; Zhan-Ping Shi; Zheng Li; Zuping He; Hong-Liang Hu; Peng Li; Shi Yang; Wei Zhang; Hui Ding; Ru-Hui Tian; Ye Ning; Ling-Ling Zhang

    2012-01-01

    Recent studies have reported that induced pluripotent stem (iPS) cells from mice and humans can differentiate into primordial germ cells.However,whether iPS cells am capable of producing male germ cells is not known.The objective of this study was to investigate the differentiation potential of mouse iPS cells into spermatogonial stem cells and late.stage male germ cells.We used an approach that combines in vitro differentiation and in vivotransplantation.Embryoid bodies (EBs) were obtained from iPS cells using leukaemia inhibitor factor (LIF)-free medium.Quantitative PCR revealed a decrease in Oct4 expression and an increase in Stra8and Vasa mRNA in the EBs derived from iPS cells.iPS cell-derived EBs were induced by retinoic acid to differentiate into spermatogonial stem cells (SSCs),as evidenced by their expression of VASA,as well as CDH 1 and GFRα 1,which are markers of SSCs.Furthermore,these germ cells derived from iPS cells were transplanted into recipient testes of mice that had been pre-treated with busulfan.Notably,iPS cell-derived SSCs were able to differentiate into male germ cells ranging from spermatogonia to round spermatids,as shown by VASA and SCP3 expression.This study demonstrates that iPS cells have the potential to differentiate into late-stage male germ cells.The derivation of male germ cells from iPS cells has potential applications in the treatment of male infertility and provides a model for uncovering the molecular mechanisms underlying male germ cell development.

  4. 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)

    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

  5. DNA single-strand breaks, double-strand breaks, and crosslinks in rat testicular germ cells: Measurements of their formation and repair by alkaline and neutral filter elution

    International Nuclear Information System (INIS)

    This work describes a neutral and alkaline elution method for measuring DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-DNA crosslinks in rat testicular germ cells after treatments in vivo or in vitro with both chemical mutagens and gamma-irradiation. The methods depend upon the isolation of testicular germ cells by collagenase and trypsin digestion, followed by filtration and centrifugation. 137Cs irradiation induced both DNA SSBs and DSBs in germ cells held on ice in vitro. Irradiation of the whole animal indicated that both types of DNA breaks are induced in vivo and can be repaired. A number of germ cell mutagens induced either DNA SSBs, DSBs, or cross-links after in vivo and in vitro dosing. These chemicals included methyl methanesulfonate, ethyl methanesulfonate, ethyl nitrosourea, dibromochlorpropane, ethylene dibromide, triethylene melamine, and mitomycin C. These results suggest that the blood-testes barrier is relatively ineffective for these mutagens, which may explain in part their in vivo mutagenic potency. This assay should be a useful screen for detecting chemical attack upon male germ-cell DNA and thus, it should help in the assessment of the mutagenic risk of chemicals. In addition, this approach can be used to study the processes of SSB, DSB, and crosslink repair in DNA of male germ cells, either from all stages or specific stages of development

  6. Cholesterol induces proliferation of chicken primordial germ cells.

    Science.gov (United States)

    Chen, Dongyang; Chen, Meijuan; Lu, Zhenping; Yang, Mengmeng; Xie, Long; Zhang, Wenxin; Xu, Huiyan; Lu, Kehuan; Lu, Yangqing

    2016-08-01

    Primordial germ cells (PGCs) are the precursors of sperm and eggs and may serve as suitable cells for use in research in developmental biology and transgenic animals. However, the long-term propagation of PGCs in vitro has so far been plagued by the loss of their germ cell characteristics. This is largely because of the scarcity of knowledge concerning cell division and proliferation in these cells and the poor optimization of the culture medium. The sonic hedgehog (SHH) signaling pathway is involved in proliferation of many types of cells, but little is known about its role in chicken PGCs. The results of the current study indicate that the proliferation of chicken PGCs increases significantly when cholesterol, a molecule that facilitates the trafficking of HH ligands, is supplemented in the culture medium. This effect was attenuated when an SHH antagonist, cyclopamine was added, suggesting the involvement of SHH signaling in this process. The characterization of PGCs treated with cholesterol has shown that these cells express germ-cell-related markers and retain their capability to colonize the embryonic gonad after re-introduction to vasculature of stage-15 HH embryos, indicating that proliferation of PGCs induced by cholesterol does not alter the germ cell characteristics of these cells. PMID:27269880

  7. Cytogenetics of a malignant ovarian germ-cell tumor

    NARCIS (Netherlands)

    van Echten, J; van Doorn, LC; van der Linden, HC; van der Veen, AY; de Jong, B

    1998-01-01

    Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ-cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal st

  8. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies pr

  9. Infantile and adult testicular germ cell tumors : a different pathogenesis?

    NARCIS (Netherlands)

    van Echten, J; Timmer, A; van der Veen, AY; Molenaar, WM; de Jong, B

    2002-01-01

    Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore. these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of t

  10. Characterisation and germline transmission of cultured avian primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Joni Macdonald

    Full Text Available BACKGROUND: Avian primordial germ cells (PGCs have significant potential to be used as a cell-based system for the study and preservation of avian germplasm, and the genetic modification of the avian genome. It was previously reported that PGCs from chicken embryos can be propagated in culture and contribute to the germ cell lineage of host birds. PRINCIPAL FINDINGS: We confirm these results by demonstrating that PGCs from a different layer breed of chickens can be propagated for extended periods in vitro. We demonstrate that intracellular signalling through PI3K and MEK is necessary for PGC growth. We carried out an initial characterisation of these cells. We find that cultured PGCs contain large lipid vacuoles, are glycogen rich, and express the stem cell marker, SSEA-1. These cells also express the germ cell-specific proteins CVH and CDH. Unexpectedly, using RT-PCR we show that cultured PGCs express the pluripotency genes c-Myc, cKlf4, cPouV, cSox2, and cNanog. Finally, we demonstrate that the cultured PGCs will migrate to and colonise the forming gonad of host embryos. Male PGCs will colonise the female gonad and enter meiosis, but are lost from the gonad during sexual development. In male hosts, cultured PGCs form functional gametes as demonstrated by the generation of viable offspring. CONCLUSIONS: The establishment of in vitro cultures of germline competent avian PGCs offers a unique system for the study of early germ cell differentiation and also a comparative system for mammalian germ cell development. Primary PGC lines will form the basis of an alternative technique for the preservation of avian germplasm and will be a valuable tool for transgenic technology, with both research and industrial applications.

  11. Mitogen-Activated Protein Kinase Signaling in Male Germ Cell Apoptosis in the Rat1

    OpenAIRE

    Jia, Yue; Castellanos, Jesse; Wang, Christina; Sinha-Hikim, Indrani; Lue, YanHe; Swerdloff, Ronald S.; Sinha-Hikim, Amiya P.

    2008-01-01

    Programmed germ cell death is critical for functional spermatogenesis. Increased germ cell apoptosis can be triggered by various regulatory stimuli, including testicular hyperthermia or deprivation of gonadotropins and intratesticular testosterone. We have previously shown the involvement of the mitogen-activated protein kinase (MAPK) 14 in apoptotic signaling of male germ cells across species after hormone deprivation. This study investigates the role of MAPK14 in germ cell apoptosis in rats...

  12. The PUF binding landscape in metazoan germ cells

    Science.gov (United States)

    Prasad, Aman; Porter, Douglas F.; Kroll-Conner, Peggy L.; Mohanty, Ipsita; Ryan, Anne R.; Crittenden, Sarah L.; Wickens, Marvin; Kimble, Judith

    2016-01-01

    PUF (Pumilio/FBF) proteins are RNA-binding proteins and conserved stem cell regulators. The Caenorhabditis elegans PUF proteins FBF-1 and FBF-2 (collectively FBF) regulate mRNAs in germ cells. Without FBF, adult germlines lose all stem cells. A major gap in our understanding of PUF proteins, including FBF, is a global view of their binding sites in their native context (i.e., their “binding landscape”). To understand the interactions underlying FBF function, we used iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) to determine binding landscapes of C. elegans FBF-1 and FBF-2 in the germline tissue of intact animals. Multiple iCLIP peak-calling methods were compared to maximize identification of both established FBF binding sites and positive control target mRNAs in our iCLIP data. We discovered that FBF-1 and FBF-2 bind to RNAs through canonical as well as alternate motifs. We also analyzed crosslinking-induced mutations to map binding sites precisely and to identify key nucleotides that may be critical for FBF–RNA interactions. FBF-1 and FBF-2 can bind sites in the 5′UTR, coding region, or 3′UTR, but have a strong bias for the 3′ end of transcripts. FBF-1 and FBF-2 have strongly overlapping target profiles, including mRNAs and noncoding RNAs. From a statistically robust list of 1404 common FBF targets, 847 were previously unknown, 154 were related to cell cycle regulation, three were lincRNAs, and 335 were shared with the human PUF protein PUM2. PMID:27165521

  13. Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

    2008-01-18

    Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

  14. Adult Immunohistochemical Markers Fail to Detect Intratubular Germ Cell Neoplasia in Prepubertal Boys with Cryptorchidism

    DEFF Research Database (Denmark)

    Kvist, Kolja; Clasen-Linde, Erik; Cortes, Dina;

    2013-01-01

    Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. It is characterized by large germ cells with large nuclei with a hyperchromatic, coarse chromatin pattern, large prominent nucleoli and abundant pale cytoplasm. In prepubertal boys these cells are located both...

  15. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    Science.gov (United States)

    2016-04-07

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  16. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors

    NARCIS (Netherlands)

    Rijlaarsdam, M.A.; Tax, D.M.J.; Gillis, A.J.M.; Dorssers, L.C.J.; Koestler, D.C.; De Ridder, J.; Looijenga, L.H.J.

    2015-01-01

    The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to

  17. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors

    NARCIS (Netherlands)

    M.A. Rijlaarsdam (Martin); D.M.J. Tax (David); A.J.M. Gillis (Ad); L.C.J. Dorssers (Lambert); Koestler, D.C. (Devin C.); De Ridder, J. (Jeroen); L.H.J. Looijenga (Leendert)

    2015-01-01

    textabstractThe cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the

  18. File list: DNS.Gon.20.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Gon.20.AllAg.Testicular_germ_cells mm9 DNase-seq Gonad Testicular germ cells ht...tp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Gon.20.AllAg.Testicular_germ_cells.bed ...

  19. File list: Unc.Gon.20.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Gon.20.AllAg.Testicular_germ_cells mm9 Unclassified Gonad Testicular germ cells... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Gon.20.AllAg.Testicular_germ_cells.bed ...

  20. Carcinoma in situ testis displays permissive chromatin modifications similar to immature foetal germ cells

    DEFF Research Database (Denmark)

    Almstrup, K; Nielsen, J E; Mlynarska, O;

    2010-01-01

    The majority of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS) stage. The CIS cell is a neoplastic counterpart of foetal germ cells. During their development, foetal germ cells undergo extensive and essential epigenetic modifications, but little is known about...

  1. Are testicular mast cells involved in the regulation of germ cells in man?

    Science.gov (United States)

    Windschüttl, S; Nettersheim, D; Schlatt, S; Huber, A; Welter, H; Schwarzer, J U; Köhn, F M; Schorle, H; Mayerhofer, A

    2014-07-01

    Protease activated receptor-2 (PAR-2) is the receptor for the prototype mast cell product tryptase. PAR-2 expression by cells of the human germinal epithelium was reported, but the exact cellular sites of testicular expression remained unknown. That became of interest, because mast cells, expressing tryptase, were found in the walls of seminiferous tubules of patients suffering from sub- and infertility. This location suggested that mast cells via tryptase might be able to influence PAR-2-expressing cells in the germinal epithelium. To explore these points, we used testicular paraffin-embedded sections for immunohistochemistry. PAR-2-positive cells were mostly basally located cells of the seminiferous epithelium, namely spermatogonia. Some stained for the receptor for GDNF (GFRalpha-1), and possibly represent spermatogonial stem cells (SSCs). As true human SSCs could not be examined, we turned to TCam-2 seminoma cells, expressing PAR-2 and stem cell markers, including GFRalpha-1. TCam-2 cells robustly responded to stimulation with a specific PAR-2 agonist (SLIGKV) by increased intracellular Ca(2+) levels. Recombinant tryptase and trypsin, but not a control peptide (VKGILS) evoked this response, implying functional PAR-2. Video imaging and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous apoptosis and increased proliferation of TCam-2 cells. The expression of the marker of pluripotency OCT3/4 was unchanged upon activation of PAR-2, suggesting that the stem cell-like character is not changed. Furthermore, human germ cell cancers were examined. A subset of seminoma and carcinoma in situ samples expressed PAR-2, indicating that yet unknown subgroups exist. Collectively, the descriptive data obtained in human testicular sections, in germ cell cancers and the functional results in TCam-2 cells imply a trophic role of mast cell-derived tryptase for human germ cells. This may be relevant for subtypes of human germ cell cancers, and possibly SSCs. It

  2. A mechanism of male germ cell apoptosis induced by bisphenol-A and nonylphenol involving ADAM17 and p38 MAPK activation.

    Directory of Open Access Journals (Sweden)

    Paulina Urriola-Muñoz

    Full Text Available Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA and Nonylphenol (NP induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1 to determine whether BPA and NP induce ADAM17 activation; and 2 to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis.

  3. Immunohistochemical study of nuclear changes associated with male germ cell death and spermiogenesis.

    Science.gov (United States)

    McClusky, Leon M; Patrick, Sean; Barnhoorn, Irene E J; van Dyk, Jacobus C; de Jager, Christiaan; Bornman, Maria S

    2009-08-01

    In a previous study on the effects of gestational and lactational exposure of para-nonylphenol on male rats, we noted in both induced and uninduced rats, that variations in cleaved caspase-3 immunostaining patterns were associated with distinct nuclear alterations in mainly basally located germ cells (spermatogonia and preleptotene spermatocytes). These were re-analysed and compared with cleaved caspase-3-labeled germ cells in the aging human and the spermatogenically active catfish testis. In the rat testes, cytoplasmic immunostaining was progressively associated with lateral compression of the nucleus, its break up into large pieces which can contain immunostained marginated chromatin masses. The pale remnants of the nucleus continued to shrink in size concomitant with the appearance of blue-purplish stained regions in the cytoplasm similar in color to the condensed chromatin in spermatids, a condition which was TUNEL-negative. These large clumps of chromatin also eventually disappeared, giving rise to cells resembling cytoplasmic ghosts, a condition which was TUNEL-positive. By contrast, the immunolabeled nuclei of human and catfish germ cells condensed into a single mass, after which they lost immunoreactivity. To exclude the possibility that these observations could reflect alterations in Sertoli nuclei, rat testicular sections were probed with a mouse anti-human GATA-4 monoclonal (MHM) antibody. The MHM was, however, the second of two GATA-4 antibodies tested, with a goat anti-mouse polyclonal (GMP) initially used to label the rat Sertoli nuclei. GMP unexpectedly, but distinctly labeled the complete development of the acrosome in the rat testis, a fortuitous finding with utility for staging of the seminiferous epithelium. PMID:19924546

  4. Electron microscopy of the germ cells and the ovarian wall in Xiphinema (Nematoda).

    Science.gov (United States)

    Van de Velde, M C; Coomans, A

    1988-01-01

    The ovary of Xiphinema theresiae is studied ultrastructurally. It consists of two cell types, the ovarian epithelial cells and the germ cells. The ovarian epithelial cells form a thin layer around the germ cells. Their nuclei are located in between the germ cells. At some sites, processes of the ovarian epithelial cells migrate inward and form a central cytoplasmic mass. The germ cells have a large lobated nucleus, with an eccentric nucleolus, and are considered to represent young previtellogenic oocytes. In contact with the central cytoplasmic mass, the germ cells develop two membrane derived features, the villi and the small coated bulges, which most probably play a role in transport.

  5. Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling

    DEFF Research Database (Denmark)

    Carl, J; Christensen, T B; von der Maase, H

    1992-01-01

    This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactate dehydrogenase (LDH...... faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses....

  6. Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

    Science.gov (United States)

    Wang, Ying; Zhou, Feng; Qian, Zhida; Qing, Jiale; Zhao, Mengdam; Huang, Lili

    2014-11-01

    We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors. PMID:25518772

  7. Germ cell transplantation: a potential treatment of severe testicular failure.

    Science.gov (United States)

    Cozzolino, D J; Lamb, D J

    2000-12-01

    Although the process of spermatogenesis is relatively efficient and resistant to damage, male infertility can result from exposure to toxic agents such as chemotherapeutic regimes, radiation, or occupational exposures to chemicals. Other types of infertility may result from migratory defects or poor survival of primordial germ cells during development, abnormal repopulation of the tubules by spermatogonia during development, or low cellularity of the testis (hypospermatogenesis). Presently, there are no effective therapies available to treat these patients. Recent studies in animal models have demonstrated that isolated testicular germ cells collected from testes may be transplanted into sterile recipient mice to regenerate spermatogenesis. This technology will have widespread applications in efforts to manipulate the genome and produce transgenic offspring, to improve agricultural species, to enhance sperm production in endangered species, to improve our understanding of the control mechanisms regulating spermatogenesis, and to treat male infertility.

  8. Mediastinal germ cell tumors: a radiologic-pathologic review

    Energy Technology Data Exchange (ETDEWEB)

    Drevelegas, A. [Dept. of Radiology, Aristoteles Univ., Thessaloniki (Greece); Palladas, P. [Dept. of Radiology, G. Papanicolaou Hospital, Thessaloniki (Greece); Scordalaki, A. [Dept. of Pathology, G. Papanicolaou Hospital, Thessaloniki (Greece)

    2001-10-01

    Germ cell tumors of the mediastinum are histologically identical to those found in the testes and ovaries. Early diagnosis and treatment improve the survival rate. Imaging studies of teratoma demonstrate a rounded, often lobulated heterogeneous mass containing soft tissue elements with fluid and fat attenuation. Calcification is present in 20-43% of cases. Seminomas are large masses of homogeneous soft tissue attenuation. Malignant nonseminomatous germ cell tumors are heterogeneous tumors with irregular borders due to invasion of adjacent structures. CT shows the location and extent of the tumors as well as intrinsic elements including soft tissue, fat, fluid, and calcification. CT is the modality of choice for the diagnostic evaluation of these tumors. MRI reveals masses of heterogeneous signal intensity, is more sensitive in depicting infiltration of the adjacent structures by fat plane obliteration, and is performed as an ancillary study. (orig.)

  9. Perchlorate Exposure Reduces Primordial Germ Cell Number in Female Threespine Stickleback.

    Science.gov (United States)

    Petersen, Ann M; Earp, Nathanial C; Redmond, Mandy E; Postlethwait, John H; von Hippel, Frank A; Buck, C Loren; Cresko, William A

    2016-01-01

    Perchlorate is a common aquatic contaminant that has long been known to affect thyroid function in vertebrates, including humans. More recently perchlorate has been shown to affect primordial sexual differentiation in the aquatic model fishes zebrafish and threespine stickleback, but the mechanism has been unclear. Stickleback exposed to perchlorate from fertilization have increased androgen levels in the embryo and disrupted reproductive morphologies as adults, suggesting that perchlorate could disrupt the earliest stages of primordial sexual differentiation when primordial germ cells (PGCs) begin to form the gonad. Female stickleback have three to four times the number of PGCs as males during the first weeks of development. We hypothesized that perchlorate exposure affects primordial sexual differentiation by reducing the number of germ cells in the gonad during an important window of stickleback sex determination at 14-18 days post fertilization (dpf). We tested this hypothesis by quantifying the number of PGCs at 16 dpf in control and 100 mg/L perchlorate-treated male and female stickleback. Perchlorate exposure from the time of fertilization resulted in significantly reduced PGC number only in genotypic females, suggesting that the masculinizing effects of perchlorate observed in adult stickleback may result from early changes to the number of PGCs at a time critical for sex determination. To our knowledge, this is the first evidence of a connection between an endocrine disruptor and reduction in PGC number prior to the first meiosis during sex determination. These findings suggest that a mode of action of perchlorate on adult reproductive phenotypes in vertebrates, including humans, such as altered fecundity and sex reversal or intersex gonads, may stem from early changes to germ cell development. PMID:27383240

  10. Perchlorate Exposure Reduces Primordial Germ Cell Number in Female Threespine Stickleback

    Science.gov (United States)

    Petersen, Ann M.; Earp, Nathanial C.; Redmond, Mandy E.; Postlethwait, John H.; von Hippel, Frank A.; Buck, C. Loren; Cresko, William A.

    2016-01-01

    Perchlorate is a common aquatic contaminant that has long been known to affect thyroid function in vertebrates, including humans. More recently perchlorate has been shown to affect primordial sexual differentiation in the aquatic model fishes zebrafish and threespine stickleback, but the mechanism has been unclear. Stickleback exposed to perchlorate from fertilization have increased androgen levels in the embryo and disrupted reproductive morphologies as adults, suggesting that perchlorate could disrupt the earliest stages of primordial sexual differentiation when primordial germ cells (PGCs) begin to form the gonad. Female stickleback have three to four times the number of PGCs as males during the first weeks of development. We hypothesized that perchlorate exposure affects primordial sexual differentiation by reducing the number of germ cells in the gonad during an important window of stickleback sex determination at 14–18 days post fertilization (dpf). We tested this hypothesis by quantifying the number of PGCs at 16 dpf in control and 100 mg/L perchlorate-treated male and female stickleback. Perchlorate exposure from the time of fertilization resulted in significantly reduced PGC number only in genotypic females, suggesting that the masculinizing effects of perchlorate observed in adult stickleback may result from early changes to the number of PGCs at a time critical for sex determination. To our knowledge, this is the first evidence of a connection between an endocrine disruptor and reduction in PGC number prior to the first meiosis during sex determination. These findings suggest that a mode of action of perchlorate on adult reproductive phenotypes in vertebrates, including humans, such as altered fecundity and sex reversal or intersex gonads, may stem from early changes to germ cell development. PMID:27383240

  11. Perchlorate Exposure Reduces Primordial Germ Cell Number in Female Threespine Stickleback.

    Directory of Open Access Journals (Sweden)

    Ann M Petersen

    Full Text Available Perchlorate is a common aquatic contaminant that has long been known to affect thyroid function in vertebrates, including humans. More recently perchlorate has been shown to affect primordial sexual differentiation in the aquatic model fishes zebrafish and threespine stickleback, but the mechanism has been unclear. Stickleback exposed to perchlorate from fertilization have increased androgen levels in the embryo and disrupted reproductive morphologies as adults, suggesting that perchlorate could disrupt the earliest stages of primordial sexual differentiation when primordial germ cells (PGCs begin to form the gonad. Female stickleback have three to four times the number of PGCs as males during the first weeks of development. We hypothesized that perchlorate exposure affects primordial sexual differentiation by reducing the number of germ cells in the gonad during an important window of stickleback sex determination at 14-18 days post fertilization (dpf. We tested this hypothesis by quantifying the number of PGCs at 16 dpf in control and 100 mg/L perchlorate-treated male and female stickleback. Perchlorate exposure from the time of fertilization resulted in significantly reduced PGC number only in genotypic females, suggesting that the masculinizing effects of perchlorate observed in adult stickleback may result from early changes to the number of PGCs at a time critical for sex determination. To our knowledge, this is the first evidence of a connection between an endocrine disruptor and reduction in PGC number prior to the first meiosis during sex determination. These findings suggest that a mode of action of perchlorate on adult reproductive phenotypes in vertebrates, including humans, such as altered fecundity and sex reversal or intersex gonads, may stem from early changes to germ cell development.

  12. Mediastinal germ cell tumour with massive pulmonary involvement

    OpenAIRE

    Kawamukai, Kenji; Di Saverio, Salomone; Antonacci, Filippo; Lacava, Nicola; Boaron, Maurizio

    2011-01-01

    Multimodality treatment, with chemotherapy and surgery, is potentially curative in case of non-seminomatous germ cell tumours. The authors present the case of a primitive mediastinal GTC with bilateral lung metastases. The patient was treated with five cycles of chemotherapy. Restaging showed reduction of the extent and of 18 FDG intake and β-HCG serum levels. The patient underwent two-step surgical excision of the tumours: mediastinal lesion and 35 lung metastases were resected by a right th...

  13. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    OpenAIRE

    Stoop, Hans

    2011-01-01

    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies presented here show valuable additional information on the microscopic diagnostics in daily practice. This enables proper and complete diagnosis of this relative rare variant of cancer ensuring the b...

  14. Malignant transformation and treatment of cystic mixed germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    Yapeng Zhao; Hongyu Duan; Qinghui Zhang; Bingxin Shi; Hui Liang; Yuqi Zhang

    2016-01-01

    Objective: The authors report an extremely unusual presentation and management of a children pineal mixed germ cell tumor mainly composed of immature teratoma, aiming to summarize main theraptic points by literature review. Methods: A cystic lesion located in the rear of third ventricle in a child was detected 3 years ago with no other therapy performed except for a ventriculo-peritoneal shunt. During the following 3 years, intermitted regular brain MRI demonstrated no evidence of lesion aggrandizement. However from 20 days before admission to our institute the patient began to present acutely with exacerbating clinical symptoms meanwhile brain MRI showed signs of abrupt revulsions of initial lesion without any incentive cause. Neurological examination revealed a significant rising of serum tumor marker level. Then surgical resection was performed immediately after admission which was followed by correlative two-course chemotherapy. Results: Postoperative brain MRI demonstrated totally removing of the lesion in rear of third ventricle. Serum tumor marker level decreased remarkably after surgery and declined to normal level after two-course chemotherapy. No obvious neurological deficit occurred except for short-term memory difficulty which gradually recovered within two weeks. Soon after the second course chemotherapy the patient was currently asymptomatic and returned to school. Conclusions: (1) To ensure definitive diagnosis and proper therapecutic protocols benefit from grasping clinical features of mixed germ cell tumor. (2) Overall preoperative investigation including serum tumor marker level is as critical as neurological imaging examination. (3) Surgical excision is confirmed to be the key modality of treatment. With the regarding of mixed germ cell tumor, never highlight total resection too much. (4) Postoperative adjuvant chemotherapy is recommended as further intensive treatment to improve the prognosis of mix germ cell tumor.

  15. Genetic modification of chicken germ cells

    OpenAIRE

    Park, Tae Sub; Han, Jae Yong

    2012-01-01

    Over the past two decades numerous reports have demonstrated that the genetic modification of poultry genomes has great potential for improving poultry production; moreover, it may be used as a powerful tool for the production of industrial proteins. To date, transgenic techniques have been established for generating transgenic birds that express recombinant human proteins in hen eggs, as well as tissue-specific genes as an animal model. The production of transgenic birds is a promising appro...

  16. Gene expression profiling of chicken primordial germ cell ESTs

    Directory of Open Access Journals (Sweden)

    Lim Dajeong

    2006-08-01

    Full Text Available Abstract Background Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. Results We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. Conclusion Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.

  17. POMB/ACE chemotherapy for mediastinal germ cell tumours.

    Science.gov (United States)

    Bower, M; Brock, C; Holden, L; Nelstrop, A; Makey, A R; Rustin, G J; Newlands, E S

    1997-05-01

    Mediastinal germ cell tumours (MGCT) are rare and most published series reflect the experiences of individual institutions over many years. Since 1979, we have treated 16 men (12 non-seminomatous germ cell tumours and 4 seminomas) with newly diagnosed primary MGCT with POMB/ACE chemotherapy and elective surgical resection of residual masses. This approach yielded complete remissions in 15/16 (94%) patients. The median follow-up was 6.0 years and no relapses occurred more than 2 years after treatment. The 5 year overall survival in the non-seminomatous germ cell tumours (NSGCT) is 73% (95% confidence interval 43-90%). One patient with NSGCT developed drug-resistant disease and died without achieving remission and 2 patients died of relapsed disease. In addition, 4 patients with bulky and/or metastatic seminoma were treated with POMB/ACE. One died of treatment-related neutropenic sepsis in complete remission and one died of relapsed disease. Finally, 4 patients (2 NSGCT and 2 seminomas) referred at relapse were treated with POMB/ACE and one was successfully salvaged. The combination of POMB/ACE chemotherapy and surgery is effective management for MGCT producing high long-term survival rates.

  18. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

    Directory of Open Access Journals (Sweden)

    Prabhat S Kunwar

    2003-12-01

    Full Text Available In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR, Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

  19. Serum Organochlorine Pesticide Residues and Risk of Testicular Germ Cell Carcinoma: A Population-Based Case-Control Study

    OpenAIRE

    Mary L Biggs; Davis, Mark D.; Eaton, David L.; Weiss, Noel S.; Barr, Dana B.; Doody, David R.; Fish, Sherianne; Needham, Larry L.; Chen, Chu; Schwartz, Stephen M.

    2008-01-01

    Testicular germ cell carcinoma (TGCC) is the most common malignancy among men aged 20–34. Although the pathogenesis of TGCC is poorly understood, sub-optimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess anti-androgenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p’-DDE, and whether the p,p-DDE-TGCC association is ...

  20. Tudor and its domains: germ cell formation from a Tudor perspective

    Institute of Scientific and Technical Information of China (English)

    Travis THOMSON; Paul LASKO

    2005-01-01

    In many metazoan species, germ cell formation requires the germ plasm, a specialized cytoplasm which often contains electron dense structures. Genes required for germ cell formation in Drosophila have been isolated predominantly in screens for maternal-effect mutations. One such gene is tudor (tud); without proper tud function germ cell formation does not occur. Unlike other genes involved in Drosophila germ cell specification tud is dispensable for other somatic functions such as abdominal patterning. It is not known how TUD contributes at a molecular level to germ cell formation but in tud mutants, polar granule formation is severely compromised, and mitochondrially encoded ribosomal RNAs do not localize to the polar granule. TUD is composed of 11 repeats of the protein motif called the Tudor domain. There are similar proteins to TUD in the germ line of other metazoan species including mice. Probable vertebrate orthologues of Drosophila genes involved in germ cell specification will be discussed.

  1. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells

    DEFF Research Database (Denmark)

    Byskov, A G; Fenger, M; Westergaard, L;

    1993-01-01

    We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture...... are fixed, squashed, and DNA-stained. In these preparations germ cells and somatic cells can be distinguished, and the number of germ cells in the different stages of meiosis is counted as is the number of somatic cells in mitosis. MIS activity is defined to be present in a medium when meiosis is induced...... in male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media...

  2. Forskolin and the meiosis inducing substance synergistically initiate meiosis in fetal male germ cells

    DEFF Research Database (Denmark)

    Byskov, A G; Fenger, M; Westergaard, L;

    1993-01-01

    are fixed, squashed, and DNA-stained. In these preparations germ cells and somatic cells can be distinguished, and the number of germ cells in the different stages of meiosis is counted as is the number of somatic cells in mitosis. MIS activity is defined to be present in a medium when meiosis is induced......We have shown that Meiosis Inducing Substance (MIS) and forskolin synergistically and dose dependently induce meiosis in germ cells of cultured fetal mouse testes. We used a bioassay which consists of fetal mouse testes and ovaries cultured for 6 days. In this study MIS media are spent culture...... in male germ cells during culture. We found that MIS media as well as forskolin induced meiosis in fetal male germ cells in a dose-dependent manner. In addition, MIS media and forskolin acted synergistically by inducing meiosis. Female germ cells seem to be unaffected by the various culture media...

  3. Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

    Energy Technology Data Exchange (ETDEWEB)

    Wyrobek, A J; Schmid, T E; Marchetti, F

    2004-06-15

    Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm of mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.

  4. Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Sonne, Si Brask; Ottesen, Anne Marie;

    2008-01-01

    into virtually any type of tissue and form teratomas (non-seminomas). CIS cells display a close phenotypic similarity to fetal germ cells (primordial germ cells or gonocytes) suggesting an origin due to a developmental delay or arrest of differentiation of early germ cells. The pluripotency of these neoplasms...... in the hormonal microenvironment of the differentiating gonads may results in both the neoplasia and a host of other problems later in life, such as genital malformations, decreased spermatogenesis, and signs of hypogonadism....

  5. Malignant mixed germ cell tumor of ovary: a rare case report

    OpenAIRE

    Bhawana Tiwary; Hemali Heidi Sinha; Vivek K. Pandey

    2015-01-01

    Ovarian germ cell tumors are very rare and affect mainly young girls and women. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumors. The two histological groups are: dysgerminomas and non dysgerminomatous tumors. We report a case of a 29 years old multiparous woman who presented with persistent pain abdomen and was diagnosed to have a malignant mixed germ cell tumor comprising of both dysgerminoma and yolk sac tumor (endodermal sinus tumor...

  6. Giant germ cell tumor with mediastinal localization: A report of two cases

    Directory of Open Access Journals (Sweden)

    Fatih Meteroğlu

    2010-06-01

    Full Text Available Germ celled tumors frequently localize in anterior mediastinum.In this study we presented two germ cell tumors with different localization and huge size. We discussed two cases with germ cell tumors operated in our clinic togetherwith literature findings. Chest x-ray, computerized tomography (CT and transthorasic tru-cut biopsy were used for diagnosis. The huge intratorasic teratomas are rarely seen and surgical full resection is the most importantfactor in survival.

  7. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    OpenAIRE

    Kumar, Saurabh; Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case present...

  8. A perspective on the evolution of germ-cell development and germinal mosaics of deleterious mutations.

    Science.gov (United States)

    Woodruff, Ronny C; Balinski, Michael A; Bouzat, Juan L

    2015-10-01

    In many animals a small number of primordial germ cells (PGCs) are set aside early in development, mitosis and mitochondrial DNA syntheses are arrested, transcription is stopped or reduced, and the PGCs migrate later to the emerging gonads and become germ cells. What could be the evolutionary advantage of sequestering non-dividing PGCs early in development? A commonly cited advantage is a reduction in the number of new deleterious mutations that would occur if there were additional divisions in PGCs early in development. We would like to add to this advantage the fact that these additional mutations in PGCs give rise to germinal mosaics (i.e., premeiotic clusters of mutation) in multiple progeny of the same individual, thus having a larger detrimental effect on the evolutionary fitness of their carriers. Here, we reviewed published studies providing evidence that germinal mosaics of deleterious mutant alleles are not rare, occur for all types of genetic damage, and have been observed in all tested organisms and in nature. We propose the hypothesis that PGC sequestration during early animal development may have evolved in part in response to selection for preventing the occurrence of premeiotic clusters of deleterious mutant alleles, and describe a series of predictions that would allow the assessment of the potential role of germinal mosaics on the evolution of PGC sequestration.

  9. Germ cell development in the Honeybee (Apis mellifera; Vasa and Nanos expression

    Directory of Open Access Journals (Sweden)

    Dearden Peter K

    2006-02-01

    Full Text Available Abstract Background Studies of specification of germ-cells in insect embryos has indicated that in many taxa the germ cells form early in development, and their formation is associated with pole plasm, germ plasm or an organelle called the oosome. None of these morphological features associated with germ cell formation have been identified in the Honeybee Apis mellifera. In this study I report the cloning and expression analysis of Honeybee homologues of vasa and nanos, germ cell markers in insects and other animals. Results Apis vasa and nanos RNAs are present in early honeybee embryos, but the RNAs clear rapidly, without any cells expressing these germ cell markers past stage 2. These genes are then only expressed in a line of cells in the abdomen from stage 9 onwards. These cells are the developing germ cells that are moved dorsally by dorsal closure and are placed in the genital ridge. Conclusion This study of the expression of germ cell markers in the honeybee implies that in this species either germ cells are formed by an inductive event, late in embryogenesis, or they are formed early in development in the absence of vasa and nanos expression. This contrasts with germ cell development in other members of the Hymenoptera, Diptera and Lepidoptera.

  10. Formation and cultivation of medaka primordial germ cells.

    Science.gov (United States)

    Li, Zhendong; Li, Mingyou; Hong, Ni; Yi, Meisheng; Hong, Yunhan

    2014-07-01

    Primordial germ cell (PGC) formation is pivotal for fertility. Mammalian PGCs are epigenetically induced without the need for maternal factors and can also be derived in culture from pluripotent stem cells. In egg-laying animals such as Drosophila and zebrafish, PGCs are specified by maternal germ plasm factors without the need for inducing factors. In these organisms, PGC formation and cultivation in vitro from indeterminate embryonic cells have not been possible. Here, we report PGC formation and cultivation in vitro from blastomeres dissociated from midblastula embryos (MBEs) of the fish medaka (Oryzias latipes). PGCs were identified by using germ-cell-specific green fluorescent protein (GFP) expression from a transgene under the control of the vasa promoter. Embryo perturbation was exploited to study PGC formation in vivo, and dissociated MBE cells were cultivated under various conditions to study PGC formation in vitro. Perturbation of somatic development did not prevent PGC formation in live embryos. Dissociated MBE blastomeres formed PGCs in the absence of normal somatic structures and of known inducing factors. Most importantly, under culture conditions conducive to stem cell derivation, some dissociated MBE blastomeres produced GFP-positive PGC-like cells. These GFP-positive cells contained genuine PGCs, as they expressed PGC markers and migrated into the embryonic gonad to generate germline chimeras. Our data thus provide evidence for PGC preformation in medaka and demonstrate, for the first time, that PGC formation and derivation can be obtained in culture from early embryos of medaka as a lower vertebrate model.

  11. Cryopreservation of specialized chicken lines using cultured primordial germ cells.

    Science.gov (United States)

    Nandi, S; Whyte, J; Taylor, L; Sherman, A; Nair, V; Kaiser, P; McGrew, M J

    2016-08-01

    Biosecurity and sustainability in poultry production requires reliable germplasm conservation. Germplasm conservation in poultry is more challenging in comparison to other livestock species. Embryo cryopreservation is not feasible for egg-laying animals, and chicken semen conservation has variable success for different chicken breeds. A potential solution is the cryopreservation of the committed diploid stem cell precursors to the gametes, the primordial germ cells ( PGCS: ). Primordial germ cells are the lineage-restricted cells found at early embryonic stages in birds and form the sperm and eggs. We demonstrate here, using flocks of partially inbred, lower-fertility, major histocompatibility complex- ( MHC-: ) restricted lines of chicken, that we can easily derive and cryopreserve a sufficient number of independent lines of male and female PGCs that would be sufficient to reconstitute a poultry breed. We demonstrate that germ-line transmission can be attained from these PGCs using a commercial layer line of chickens as a surrogate host. This research is a major step in developing and demonstrating that cryopreserved PGCs could be used for the biobanking of specialized flocks of birds used in research settings. The prospective application of this technology to poultry production will further increase sustainability to meet current and future production needs. PMID:27099306

  12. Expression of Transcription Factors and Nuclear Receptors in Mixed Germ Cell-Sex Cord Stromal Tumor and Related Tumors of the Gonads.

    Science.gov (United States)

    Roth, Lawrence M; Cheng, Liang

    2015-11-01

    In this study, we compare the expression of OCT4, SALL4, and TSPYL1 in mixed germ cell-sex cord stromal tumor (MGC-SCST) of either gonad to that of normal adult testis, classic and spermatocytic seminoma, intratubular germ cell neoplasia, unclassified, gonadoblastoma, and dysgerminoma to determine the entity or entities that most closely resemble MGC-SCST by immunohistochemistry of germ cells. The most useful transcription factor was OCT4. In addition, to its already described value in distinguishing germinoma and embryonal carcinoma from yolk sac tumor and in differentiating classic from spermatocytic seminoma, we found that OCT4 is useful in confirming or ruling out potential malignancy in MGC-SCST of either gonad. Expression of OCT4 in most ovarian MGC-SCSTs resembles that of dysgerminoma, whereas most testicular examples resemble that of spermatocytic seminoma and normal adult testis. Thus, most MGC-SCSTs of the ovary are potentially malignant, and corresponding tumors of the testis are mostly benign; however, exceptions likely can be detected by the use of OCT4, potentially leading to more appropriate clinical management in some cases. SALL4 is an underutilized transcription factor that is useful in distinguishing testicular MGC-SCST from sex cord stromal tumor, unclassified in those neoplasms where the germ cells are sparse or unevenly distributed. Compared with other transcription factors studied, TSPY and its congener TSPYL1 have little value in the assessment of germ cell tumors because of their relatively wide range of expression in normal adult testis and in germ cell tumors. PMID:26107563

  13. nanos function is essential for development and regeneration of planarian germ cells.

    Science.gov (United States)

    Wang, Yuying; Zayas, Ricardo M; Guo, Tingxia; Newmark, Phillip A

    2007-04-01

    Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for studying these questions. They can regenerate germ cells from fragments of adult tissues that lack reproductive structures, suggesting that inductive signaling is involved in planarian germ cell specification. To study the development and regeneration of planarian germ cells, we have functionally characterized an ortholog of nanos, a gene required for germ cell development in diverse organisms, from Schmidtea mediterranea. In the hermaphroditic strain of this species, Smed-nanos mRNA is detected in developing, regenerating, and mature ovaries and testes. However, it is not detected in the vast majority of newly hatched planarians or in small tissue fragments that will ultimately regenerate germ cells, consistent with an epigenetic origin of germ cells. We show that Smed-nanos RNA interference (RNAi) results in failure to develop, regenerate, or maintain gonads in sexual planarians. Unexpectedly, Smed-nanos mRNA is also detected in presumptive testes primordia of asexual individuals that reproduce strictly by fission. These presumptive germ cells are lost after Smed-nanos RNAi, suggesting that asexual planarians specify germ cells, but their differentiation is blocked downstream of Smed-nanos function. Our results reveal a conserved function of nanos in germ cell development in planarians and suggest that these animals will serve as useful models for dissecting the molecular basis of epigenetic germ cell specification. PMID:17376870

  14. OVERREPRESENTATION OF CHROMOSOME 12P SEQUENCES AND KARYOTYPIC EVOLUTION IN I(12P)-NEGATIVE TESTICULAR GERM-CELL TUMORS REVEALED BY FLUORESCENCE IN-SITU HYBRIDIZATION

    NARCIS (Netherlands)

    SUIJKERBUIJK, RF; SINKE, RJ; MELONI, AM; PARRINGTON, JM; VANECHTEN, J; DEJONG, B; OOSTERHUIS, JW; SANDBERG, AA; VANKESSEL, AG

    1993-01-01

    Human testicular germ-cell tumors (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumors are characterized by the presence of a highly specific chromosomal abnormality, i.e., an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome is found in more than

  15. Identification of recurrent chromosomal aberrations in germ cell tumors of neonates and infants using genomewide array-based comparative genomic hybridization.

    NARCIS (Netherlands)

    Veltman, I.M.; Veltman, J.; Janssen, I.M.; Hulsbergen- van de Kaa, C.A.; Oosterhuis, W.; Schneider, D.; Stoop, H.; Gillis, A.J.M.; Zahn, S.; Looijenga, L.H.J.; Gobel, U.; Geurts van Kessel, A.H.M.

    2005-01-01

    Human germ cell tumors (GCTs) of neonates and infants comprise a heterogeneous group of neoplasms, including teratomas and yolk sac tumors with distinct clinical and epidemiologic features. As yet, little is known about the cytogenetic constitution of these tumors. We applied the recently developed

  16. Examination for intratubular germ cell neoplasia at operation for undescended testis in boys

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J; Frisch, M;

    1994-01-01

    A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including...

  17. Surgical Treatment and Outcome of Extracranial Germ Cell Tumors in Childhood

    NARCIS (Netherlands)

    A. de Backer (Antoine)

    2006-01-01

    textabstractGerm cell tumors (GCTs) are a heterogeneous group of very rare tumors, benign or malignant, which can occur from newborn to old age. They are thought to arise from primordial germ cells, and are found in a variety of sites. This thesis is composed of 2 major parts. In a first part, the

  18. Licensing of primordial germ cells for gametogenesis depends on genital ridge signaling

    NARCIS (Netherlands)

    Hu, Yueh-Chiang; Nicholls, Peter K; Soh, Y Q Shirleen; Daniele, Joseph R; Junker, Jan Philipp; van Oudenaarden, Alexander; Page, David C

    2015-01-01

    In mouse embryos at mid-gestation, primordial germ cells (PGCs) undergo licensing to become gametogenesis-competent cells (GCCs), gaining the capacity for meiotic initiation and sexual differentiation. GCCs then initiate either oogenesis or spermatogenesis in response to gonadal cues. Germ cell lice

  19. File list: Oth.Gon.05.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Gon.05.AllAg.Testicular_germ_cells mm9 TFs and others Gonad Testicular germ cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Gon.05.AllAg.Testicular_germ_cells.bed ...

  20. Erythropoietin may reduce the risk of germ cell loss in boys with cryptorchidism

    DEFF Research Database (Denmark)

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

    2001-01-01

    In boys with cryptorchidism older than 2 years a testicular biopsy at time of orchiopexy shows lack of germ cells in 10-40% of the cases. The number of spermatogonia per tubule is prognostic for subsequent fertility potential. A biopsy without germ cells is associated with 33-100% risk of inferti...

  1. Germ cell tumor located in the midline of the anterior neck.

    Science.gov (United States)

    Pirdopska, Tatyana; Terziev, Ivan; Hristova, Sv; Mladenovsky, W; Petkov, R

    2011-01-01

    Primary germ cell tumors involving midline of the anterior neck are extremely rare. Here we report a 68-year-old male who was operated due to a mass lesion in the anterior neck with infiltration of the isthmus of the thyroid gland. Histopathological examination revealed a germ cell tumor with extragonadal localization in the anterior neck infiltrating the isthmus of the thyroid gland.

  2. A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd.

    Science.gov (United States)

    Agoulnik, Alexander I; Lu, Baisong; Zhu, Qichao; Truong, Cavatina; Ty, Maria T; Arango, Nelson; Chada, Kiran K; Bishop, Colin E

    2002-11-15

    Primordial germ cells (PGCs) are the precursor of the germ cells in adult gonads. They arise extra-gonadally and migrate through somatic tissues to the presumptive genital ridges, where they proliferate and differentiate into oogonia or spermatogonia cells. Abnormalities in this developmental process can cause embryonic depletion of germ cells leading to infertility in the adult. We report here that the mouse gcd (germ cell deficient) mutant phenotype, characterized by reduced numbers of PGCs and adult sterility, is due to reduced PGC proliferation rather than aberrant migration and is caused by the partial deletion of a single novel gene, Pog (proliferation of germ cells). Pog is critical for normal PGC proliferation, starting between 9.5 and 10.25 dpc when germ cells begin to migrate to the developing genital ridge. Deletion of Pog is also accompanied by reduced embryonic body weight and, on some genetic backgrounds, embryonic lethality. Thus, in addition to being necessary for PGC proliferation, Pog may have a wider significance in early embryonic development.

  3. Germ Cell Cancer and Multiple Relapses: Toxicity and Survival

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria G.G.; Mortensen, Mette S.;

    2015-01-01

    Purpose: A small number of patients with germ cell cancer (GCC) receive more than one line of treatment for disseminated disease. The purpose of this study was to evaluate late toxicity and survival in an unselected cohort of patients who experienced relapse after receiving first-line treatment...... for disseminated disease. Methods: From the Danish Testicular Cancer database, we identified all patients who received more than one line of treatment for disseminated disease. Information about late toxicity and mortality was obtained by means of linkage to national registers. Prognostic factors for relapse...... chorionic gonadotropin as independent factors. We identified increasing age as a possible new prognostic factor for treatment failure after second-line treatment (HR, 1.2 per 10 years; 95% CI, 1.2 to 15). Conclusion: Patients with GCC who survive after more than one line of treatment for disseminated...

  4. Testicular germ cell tumors: Molecular genetic and clinicomorphological aspects

    Directory of Open Access Journals (Sweden)

    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. 

  5. Germ cells and ova in dysgenetic gonads of a 46-XY female dizygotic twin.

    Science.gov (United States)

    Cussen, L J; MacMahon, R A

    1979-04-01

    The frequency of germ cell neoplasms in girls with 46-XY gonadal dysgenesis suggests that germ cells may persist in the dysgenetic gonads for many years. A phenotypic female infant with a karyotype of 46-XY in blood, skin, and gonads had a few ova in primordial follicles and numerous germ cells in her dysgenetic gonads at the age of 3 months. At 3 years and 10 months of age her gonads contained no primordial follicle and the only remaining germ cells were in a gonadoblastoma. We propose that germ cells are lost from dysgenetic gonads much more rapidly than from normal gonads, but that the rate of loss in patients with a karyotype of 46-XY may be less than the rate of loss in patients with a karyotype of 45-XO. PMID:433851

  6. The value of positive Oct3/4 and D2-40 immunohistochemical expression in prediction of germ cell neoplasia in prepubertal boys with cryptorchidism

    DEFF Research Database (Denmark)

    Clasen-Linde, Erik; Kvist, Kolja; Cortes, Dina;

    2016-01-01

    OBJECTIVE: Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. Adult germ cell cancer immunohistochemical markers fail to detect ITGCN in prepubertal boys with congenital cryptorchidism, because positive immunohistochemistry is commonly seen below 18 months old...

  7. Dnd Is a Critical Specifier of Primordial Germ Cells in the Medaka Fish

    Directory of Open Access Journals (Sweden)

    Ni Hong

    2016-03-01

    Full Text Available Primordial germ cell (PGC specification occurs early in development. PGC specifiers have been identified in Drosophila, mouse, and human but remained elusive in most animals. Here we identify the RNA-binding protein Dnd as a critical PGC specifier in the medaka fish (Oryzias latipes. Dnd depletion specifically abolished PGCs, and its overexpression boosted PGCs. We established a single-cell culture procedure enabling lineage tracing in vitro. We show that individual blastomeres from cleavage embryos at the 32- and 64-cell stages are capable of PGC production in culture. Importantly, Dnd overexpression increases PGCs via increasing PGC precursors. Strikingly, dnd RNA forms prominent particles that segregate asymmetrically. Dnd concentrates in germ plasm and stabilizes germ plasm RNA. Therefore, Dnd is a critical specifier of fish PGCs and utilizes particle partition as a previously unidentified mechanism for asymmetric segregation. These findings offer insights into PGC specification and manipulation in medaka as a lower vertebrate model.

  8. [Complete Resection of Non-seminomatous Germ Cell Tumor with Plastron Approach].

    Science.gov (United States)

    Suzuki, Jun; Oizumi, Hiroyuki; Kato, Hirohisa; Endoh, Makoto; Watarai, Hikaru; Hamada, Akira; Suzuki, Katsuyuki; Nakahashi, Kenta; Sasage, Takayuki; Sadahiro, Mitsuaki

    2016-07-01

    A 17-year-old man was admitted to our hospital for the abnormal chest shadow. Chest computed tomography(CT) demonstrated mediastinal tumor, measuring 13 cm in diameter with high serum level of alpha fetoprotein (AFP) and human chorionic gonadotropin (hCG). The lesions were diagnosed as mixed germ cell tumors including a non-seminomatous malignant component by CT guided needle biopsy. After 5 courses of chemotherapy, the serum AFP and hCG were decreased almost normal level but the tumor size was not changed. Because it seemed to be difficult to get sufficient operating field with standard median sternotomy and patient wanted to treat funnel chest, we selected tumor resection with plastron approach. The tumor was completely resected with a good operation field by this procedure. PMID:27365059

  9. FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling

    Institute of Scientific and Technical Information of China (English)

    Zaida Sarrate; Joan Blanco; Ester Anton; Susana Egozcue; Josep Egozcue; Francesca Vidal

    2005-01-01

    Chromosome abnormalities are one of the major causes of human infertility. In infertile males, abnormal karyotypes are more frequent than in the general population. Furthermore, meiotic disorders affecting the germ cell-line have been observed in men with normal somatic karyotypes consulting for infertility. In both cases, the production of unbalanced spermatozoa has been demonstrated. Basically addressed to establish reproductive risks, fluorescence in situ hybridization (FISH) on decondensed sperm heads has become the most frequently used method to evaluate the chromosomal constitution of spermatozoa in carriers of numerical sex chromosome abnormalities, carriers of structural chromosome reorganizations and infertile males with normal karyotype. The aim of this review is to present updated figures of the information obtained through sperm FISH studies with an emphasis on its clinical significance. Furthermore, the incorporation of novel FISH-based techniques (Multiplex-FISH; Multi-FISH) in male infertility studies is also discussed.

  10. Genome wide DNA methylation profiles provide clues to the origin and pathogenesis of germ cell tumors.

    Science.gov (United States)

    Rijlaarsdam, Martin A; Tax, David M J; Gillis, Ad J M; Dorssers, Lambert C J; Koestler, Devin C; de Ridder, Jeroen; Looijenga, Leendert H J

    2015-01-01

    The cell of origin of the five subtypes (I-V) of germ cell tumors (GCTs) are assumed to be germ cells from different maturation stages. This is (potentially) reflected in their methylation status as fetal maturing primordial germ cells are globally demethylated during migration from the yolk sac to the gonad. Imprinted regions are erased in the gonad and later become uniparentally imprinted according to fetal sex. Here, 91 GCTs (type I-IV) and four cell lines were profiled (Illumina's HumanMethylation450BeadChip). Data was pre-processed controlling for cross hybridization, SNPs, detection rate, probe-type bias and batch effects. The annotation was extended, covering snRNAs/microRNAs, repeat elements and imprinted regions. A Hidden Markov Model-based genome segmentation was devised to identify differentially methylated genomic regions. Methylation profiles allowed for separation of clusters of non-seminomas (type II), seminomas/dysgerminomas (type II), spermatocytic seminomas (type III) and teratomas/dermoid cysts (type I/IV). The seminomas, dysgerminomas and spermatocytic seminomas were globally hypomethylated, in line with previous reports and their demethylated precursor. Differential methylation and imprinting status between subtypes reflected their presumed cell of origin. Ovarian type I teratomas and dermoid cysts showed (partial) sex specific uniparental maternal imprinting. The spermatocytic seminomas showed uniparental paternal imprinting while testicular teratomas exhibited partial imprinting erasure. Somatic imprinting in type II GCTs might indicate a cell of origin after global demethylation but before imprinting erasure. This is earlier than previously described, but agrees with the totipotent/embryonic stem cell like potential of type II GCTs and their rare extra-gonadal localization. The results support the common origin of the type I teratomas and show strong similarity between ovarian type I teratomas and dermoid cysts. In conclusion, we identified

  11. 32. Study the aneugenic effect of benzene on germ cell of animal and workers

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To study the aneupoidy effect of benzene on germ cells of animal and humans. Method: The NIH adult female mice were treated with varies doses of benzene (942, 1881 and 3762mg/kg respectively) by single gavage and (706, 1922 and 4864mg/m3 respectively) by inhalation (2h/d, 15d), the ovulated oocytes were collected for conventional cytogenetic analyses, and the frequencies of aneuploidy were detected. The frequencies of aneuploidy in sperm of benzene exposed workers were detected by two color fluorescence in situ hybridization with digoxingenin labeled 9 chromosome probe(D9Z1) and biotin labeled 18 chromosome probe (D18Z1). Result: The frequencies of aneuploidy in MII oocytes were significantly increased over the control in three groups treated by inhalation (7.06%,7.50% and 7.76% respectively control 1.30%, P<0.05 ), a dose-dependent response was present, But in gavage groups only the high dose group was increased over that of control. P<0.05. The timeweight average air concentration (TWA) of benzene in the workplace was 86.49mg/m3, it was two fold higher than the national maximum allowable concentration. The concentration of urinary trans, trans-muconic acid (ttMA) in exposed group was significantly higher than that of control group. A total of 136 401 sperm nuclei in 14 exposed workers and 156 955 sperm nuclei in 16 control workers were counted. The results showed that the frequencies of disomic sperm for chromosome 9 and 18, and diploidy sperm in exposed-workers (0.168%, 0.055%, 0.073%, respectively) were statistically increased over that (0.050%、 0. 033% and 0.040%, respectively) of controls. P<0.05. The frequencies of nullisomic sperm for chromosome 9,18 in the exposed group (0.206%,0.068%) were statistically increased also over that (0.067%,0.048% respectively) of control. The frequency of overall numerical chromosome aberrations (0.570%) in tbe exposed group was increased over that of control(0.218%)P<0.05.Conclusion:An increased aneuploidy

  12. Renal impairment and late toxicity in germ-cell cancer survivors

    DEFF Research Database (Denmark)

    Lauritsen, J.; Mortensen, M. S.; Kier, M. G. G.;

    2015-01-01

    Background Treatment with bleomycin–etoposide–cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large...... cohort of germ-cell cancer survivors. Patients and methods BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow......-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. Results GFR changed (ΔGFR) −11.3%, −15...

  13. Correlation between induction of meiotic delay and aneuploidy in male mouse germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Adler, I.D.; Gassner, P.; Schriever-Schwemmer, G.; Min, Zhou Ru [Institut fuer Sauugetiergenetik, Neuherberg (Germany)

    1993-12-31

    No aneuploidy assays are prescribed in any international guidelines for chemical safety testing up to now. The CEC-sponsored Aneuploidy Project has the aim to validate test methods for aneuploidy induction which could be used as screening tests. Furthermore, one of the major goals is to develop an understanding of mechanisms by which aneuploidy is induced. The present paper describes the investigation of meiotic delay and aneuploidy induction with the drug diazepam (DZ), the environmentally important mutagen acrylamide (AA) and the spindle poison colchicine (COL), which is used as a positive control. The time course of events was investigated. It is concluded that the assessment of meiotic delay can be used to preselect chemicals which require evaluation of aneuploidy induction during MMI in male germ cells.

  14. Effects of 17beta-estradiol on distribution of primordial germ cell migration in male chicks

    Institute of Scientific and Technical Information of China (English)

    Xiu-Mei Jin; Yi-Xiang Zhang; Zan-Dong Li

    2008-01-01

    Aim: To assess whether exogenous estradiol has any effect on migration of primordial germ cells (PGCs) in the chick. Methods: Fertilized eggs were treated with 17beta-estradiol (Ez) (80 lag/egg) at stage X (day 0 of incubation),stages 8-10 (incubation 30 h) and 13-15 (incubation 55 h). Controls received vehicle (emulsion) only. Changes in PGC number were measured on different days according to developmental stages. Results: In male right gonads,but not in female left gonads, at stages 28-30 (incubation 132 h) significant decreases in the mean number of PGCs aggregating were observed compared with the controls (P 0.05). Conclusion: The present study provides evidence that E2 has significant effects on the localization of PGCs in male fight, but not female left, gonads of chicken embryos at stages28-30, compared with controls.

  15. MAPK15 upregulation promotes cell proliferation and prevents DNA damage in male germ cell tumors

    Science.gov (United States)

    Ilardi, Gennaro; Acunzo, Mario; Nigita, Giovanni; Sasdelli, Federica; Celetti, Angela; Strambi, Angela; Staibano, Stefania; Croce, Carlo Maria; Chiariello, Mario

    2016-01-01

    Germ cell tumors (GCT) are the most common malignancies in males between 15 and 35 years of age. Despite the high cure rate, achieved through chemotherapy and/or surgery, the molecular basis of GCT etiology is still largely obscure. Here, we show a positive correlation between MAPK15 (ERK8; ERK7) expression and specific GCT subtypes, with the highest levels found in the aggressive embryonal carcinomas (EC). Indeed, in corresponding cellular models for EC, MAPK15 enhanced tumorigenicity in vivo and promoted cell proliferation in vitro, supporting a role for this kinase in human GCT. At molecular level, we demonstrated that endogenous MAPK15 is necessary to sustain cell cycle progression of EC cells, by limiting p53 activation and preventing the triggering of p53-dependent mechanisms resulting in cell cycle arrest. To understand MAPK15-dependent mechanisms impinging on p53 activation, we demonstrate that this kinase efficiently protects cells from DNA damage. Moreover, we show that the ability of MAPK15 to control the autophagic process is necessary for basal management of DNA damage and for tumor formation controlled by the kinase. In conclusion, our findings suggest that MAPK15 overexpression may contribute to the malignant transformation of germ cells by controlling a “stress support” autophagic pathway, able to prevent DNA damage and the consequent activation of the p53 tumor suppressor. Moreover, in light of these results, MAPK15-specific inhibitors might represent new tools to enhance the therapeutic index of cytotoxic therapy in GCT treatment, and to increase the sensitivity to DNA-damaging drugs in other chemotherapy-resistant human tumors. PMID:26988910

  16. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    OpenAIRE

    Al-Jumaily Usama; Al-Hussaini Maysa; Ajlouni Fatenah; Abulruz Abdulrahman; Sultan Iyad

    2012-01-01

    Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell...

  17. Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, E; Poll, S N; Goukasian, I;

    2007-01-01

    -type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1-4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern......; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found...... in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated...

  18. Melphalan, Carboplatin, Mannitol, and Sodium Thiosulfate in Treating Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors

    Science.gov (United States)

    2016-04-28

    Adult Central Nervous System Germ Cell Tumor; Adult Ependymoblastoma; Adult Medulloblastoma; Adult Pineoblastoma; Adult Supratentorial Primitive Neuroectodermal Tumor; Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Germ Cell Tumor; Childhood Ependymoblastoma; Medulloepithelioma; Ototoxicity; Recurrent Adult Brain Neoplasm; Recurrent Childhood Central Nervous System Embryonal Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor

  19. Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors

    NARCIS (Netherlands)

    L.H.J. Looijenga (Leendert); R.J.H.L.M. van Gurp (Ruud); J.M. Nesland; J.A. Stoop (Hans); A.J.M. Gillis (Ad); C.A. de Gouveia Brazao; E. Olah; J.W. Oosterhuis (Wolter); R.F.A. Weber (Robert); W.J. Kirkels (Wim); G. Lajos; S.D. Fossa (Sophie); H. de Leeuw; M. van Oorschot; M.M. von Lindern (Marieke); T.B. van Dijk (Thamar); P.J.M. Valk (Peter)

    2003-01-01

    textabstractTesticular germ-cell tumors (TGCTs) of adolescents and adults originate from intratubular germ cell neoplasia (ITGCN), which is composed of the malignant counterparts of embryonal germ cells. ITGCN cells are characterized, among others, by the presence of stem cell fact

  20. A rare case of combined placental site trophoblastic tumour with mature cystic teratoma and mixed germ cell tumour in the testis.

    Science.gov (United States)

    Leow, Wei Qiang; Loh, Hwai Liang Alwin; Lee, Lui Shiong; Goh, Chin Hong Ronald

    2015-08-01

    A 20-year-old male presented with persistent right testicular pain. Following ultrasound detection of testicular nodules and biopsy for intraoperative consultation which yielded germ cell tumour, he underwent radical orchidectomy. A predominantly whitish cyst and a lobulated, variegated nodule were identified. Histology showed a mature cystic teratoma with a focus of infiltrative epithelioid cells containing eosinophilic cytoplasm and pleomorphic nuclei, invading ectatic vessel wall associated with fibrinoid change. These cells were positive for cytokeratin, human placental lactogen and inhibin, while negative for Melan-A, p63 and alpha-fetoprotein, consistent with placental site trophoblastic tumor (PSTT). The variegated nodule was a mixed germ cell tumour composed of embryonal carcinoma and immature teratoma. Aside from choriocarcinoma, primary trophoblastic tumors such as PSTT, which are derived from intermediate trophoblasts, are extremely rare in the testis. Aside from a case of pure testicular PSTT, 2 other cases have been described in association with germ cell tumour, of which one is a mature teratoma with PSTT that demonstrated gain of chromosome 12p. The other presented with PSTT in retroperitoneal recurrence of a testicular mixed germ cell tumour. We discussed the features of this tumour in the testis and important differentials in its diagnosis.

  1. Improved Isolation and Culture of Embryonic Germ Cells from Guanzhong Dairy Goat

    Institute of Scientific and Technical Information of China (English)

    YANG Wei-feng; GE Xiu-guo; HUA Jin-lian; SHEN Wen-zheng; DOU Zhong-ying

    2006-01-01

    A total of 219 embryonic-germ-cell-like (EG-like) clumps were derived from 15 selected goat fetuses. Isolation of primordial germ cells (PGCs) based on co-culture with primary goat embryonic fibroblast showed no difference from traditional feeder layer-based culture method used in mouse and human. The putative primary EG colonies were multilayer clumps of compact cells with unclear cell-cell boundaries. Three subculture methods of goat EG-like colony, traditional enzymatic digestion, mechanical cutting and combination of the both, were compared in this study. As a result, EG-like colonies traditionally disassociated with collagenase Ⅳ could be subcultured for up to 4 passages. And the mechanically disaggregated EG-like colonies were successfully maintained 9-12 passages with or without enzymatic treatment. The pluripotency of the EG-like colonies was identified by their specific marker staining, spontaneous differentiation and embryoid bodies (EBs) formation in vitro. Most goat EG-like colonies (> 80%) were AKP positive and immunocytochemically characterized with positive SSEA-1, Oct-4 and c-kit staining but SSEA-4. Under the condition of delaying passage, goat EG-like cells could differentiate into fibroblast-like, epithelium-like, and neuron-like cells. In addition, EBs could be obtained successfully in routine hanging drop culture. The serum free culture system (feeder layer-based) used in this study was suitable for keeping PGCs and EG-like cells in their undifferentiated condition, but failed to converse them to immortal cells. These results indicated that mechanical cutting is an effective method for passaging goat EG cell colonies.However, the microenvironment of conversing EG cells to immortal cells is still unclear.

  2. Malignant ovarian germ cell tumors at a tertiary care setting in pakistan

    International Nuclear Information System (INIS)

    Background: Malignant Ovarian Germ Cell Tumours (MOGCT) are rare neoplasms and their behavior is unknown in South-East Asian population. Method: Case records of 66 patients from 1994-2007 with MOGCT were reviewed. Histology was based on WHO classification. Tumours were staged according to International Federation of Gynecology and Obstetrics (FIGO) system. Data was collected on age, histopathology, stage, alpha-feto protein (AFP) and B-human chorionic gonadotropins (B-hCG) levels, treatment, time to recurrence (TTR) and overall survival (OS). OS was the interval in months between date of diagnosis and last encounter while TTR was between the date of diagnosis and recurrence. OS was determined by Kaplan-Meier method. Results: Median age of our patients was 18 years. Ninteen patients were in stage I, eight in II, twenty-one in III and eighteen in stage IV. Histologically, dysgerminoma was the most common diagnosis (22 patients) followed by teratoma in 16, yolk sac tumor in 15, mixed germ cell tumor in 12 while embryonal carcinoma was identified in only one patient. Median followup was 48 months (0.2-183). All patients underwent initial surgery. Fertility sparing procedures were performed in 75 percentage patients. Thirty-four patients (57.62 percentage) achieved complete remission while 16 (27.11 percentage) had progressive disease. Seven (10.60 percentage) patients relapsed, all within first 3 years. TTR was 11.2-32.5 months. OS for study population was 60 months. Sixteen (88 percentage) of stage I while only 4 (26.6 percentage) of stage IV patients were alive at median follow-up. Conclusions: MOGCT has good prognosis with conservative surgery and platinum chemotherapy. Fertility sparing surgery has become a standard in MOGCTs, so awareness should be raised amongst professionals for early referral to cancer care facility. (author)

  3. Testicular germ cell sensitivity to TRAIL-induced apoptosis is dependent upon p53 expression and is synergistically enhanced by DR5 agonistic antibody treatment.

    Science.gov (United States)

    McKee, Chad M; Ye, Yang; Richburg, John H

    2006-12-01

    The ability of the TRAIL/DR5 signaling pathway to induce apoptosis has generally been limited to tumor cells. Here we report that in primary testis explants, addition of TRAIL (0.5 mug/ml) caused a three-fold increase in germ cell apoptosis. Furthermore, exposure of C57BL/6 mice to the testicular toxicant, mono-(2-ethylhexyl) phthalate (MEHP), caused an increased p53 stability and elevated DR5 mRNA levels coincident with increases in the levels of apoptosis in spermatocytes. To further assess the mechanisms responsible for the sensitivity of germ cells to undergo TRAIL/DR5-mediated apoptosis, we used the germ cell lines GC-1spg and GC-2spd(ts) (a temperature sensitive spermatocyte-like cell line that allows for p53 nuclear localization at 32 degrees C but not 37 degrees C). Addition of TRAIL and the anti-DR5 monoclonal antibody, MD5-1, triggered a robust synergistic increase of apoptosis in p53 permissive GC-2 cells (32 degrees C) but not in GC-1 cells. In addition, DR5 levels on the plasma membrane of permissive cells were considerably enhanced concomitant with p53 expression and after MD5-1 treatment. These data represent the first indication that testicular germ cells, specifically spermatocytes, can undergo TRAIL-mediated apoptosis and the clinically relevant observation that pretreatment with a DR5 monoclonal antibody can greatly sensitize their apoptotic response to TRAIL.

  4. Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

    Directory of Open Access Journals (Sweden)

    Nakkrasae La-Iad

    2008-05-01

    Full Text Available Abstract Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7 is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

  5. Malignant mixed germ cell tumor of ovary: a rare case report

    Directory of Open Access Journals (Sweden)

    Bhawana Tiwary

    2015-04-01

    Full Text Available Ovarian germ cell tumors are very rare and affect mainly young girls and women. One of the most remarkable advances in oncology is in the treatment of malignant ovarian germ cell tumors. The two histological groups are: dysgerminomas and non dysgerminomatous tumors. We report a case of a 29 years old multiparous woman who presented with persistent pain abdomen and was diagnosed to have a malignant mixed germ cell tumor comprising of both dysgerminoma and yolk sac tumor (endodermal sinus tumor. [Int J Reprod Contracept Obstet Gynecol 2015; 4(2.000: 511-513

  6. Mixed germ cell tumour of testis: a case report with review of literature

    Directory of Open Access Journals (Sweden)

    S. V. Kumar

    2015-01-01

    Full Text Available Testicular tumours are rare neoplasm. Mixed germ cell tumour is the most common histological variant. Essentially, any admixture of the germ cell tumours as seen in pure form may be seen, one of the most common admixtures being embryonal carcinoma and teratoma. Unfortunately many of these patients present late usually with some complications. We present a rare case of mixed germ cell tumour with predominant embryonal carcinoma and yolk sac tumour in adolescent patient with multiple metastatic foci at the time of presentation. [Int J Res Med Sci 2015; 3(1.000: 327-330

  7. Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Rechnitzer, Catherine; Brok, Jesper S;

    2014-01-01

    Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature...... transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from...... of pathogenesis of these fascinating tumors....

  8. Primary, non-exophytic, optic nerve germ cell tumors.

    Science.gov (United States)

    DiLuna, Michael L; Two, Aimee M; Levy, Gillian H; Patel, Toral; Huttner, Anita J; Duncan, Charles C; Piepmeier, Joseph M

    2009-12-01

    Tumors of the optic chiasm are relatively uncommon and usually associated with phakomatoses such as neurofibromatosis. Even more rare is the presentation of a primary, non-exophytic, isolated optic chiasm germ cell tumor (GCT). These tumors have imaging characteristics nearly indistinguishable from optic chiasmatic gliomas (OCGs). Herein we describe two cases of young men who presented with similar findings of progressive, painless visual loss and hypothalamic-pituitary-adrenal axis dysfunction including diabetes insipidus. Brain imaging was non-diagnostic and suggestive of an OCG. Pathology demonstrated GCTs in each case highlighting the importance of biopsy confirmation of the diagnosis. Both patients underwent a pterional craniotomy and sub-frontal approach to the optic chiasm. The chiasm was diffusely enlarged and discolored in each case without evidence of sellar, suprasellar or perichiasmatic pathology. Pathology demonstrated a malignant mixed GCT in the first patient and a germinoma in the second. This case series highlights the importance of tissue biopsy for patients with progressive symptoms from optic chiasm tumors. Furthermore, this is the first report of a primary, non-exophytic malignant mixed GCT. As the treatment regimens differ widely between optic chiasm GCTs and chiasm gliomas, tissue diagnosis is important. PMID:19554263

  9. Testicular structure and germ cells morphology in salamanders

    Science.gov (United States)

    Uribe, Mari Carmen; Mejía-Roa, Víctor

    2014-01-01

    Testes of salamanders or urodeles are paired elongated organs that are attached to the dorsal wall of the body by a mesorchium. The testes are composed of one or several lobes. Each lobe is morphologically and functionally a similar testicular unit. The lobes of the testis are joined by cords covered by a single peritoneal epithelium and subjacent connective tissue. The cords contain spermatogonia. Spermatogonia associate with Sertoli cells to form spermatocysts or cysts. The spermatogenic cells in a cyst undergo their development through spermatogenesis synchronously. The distribution of cysts displays the cephalo-caudal gradient in respect to the stage of spermatogenesis. The formation of cysts at cephalic end of the testis causes their migration along the lobules to the caudal end. Consequently, the disposition in cephalo-caudal regions of spermatogenesis can be observed in longitudinal sections of the testis. The germ cells are spermatogonia, diploid cells with mitotic activity; primary and second spermatocytes characterized by meiotic divisions that develop haploid spermatids; during spermiogenesis the spermatids differentiate to spermatozoa. During spermiation the cysts open and spermatozoa leave the testicular lobules. After spermiation occurs the development of Leydig cells into glandular tissue. This glandular tissue regressed at the end of the reproductive cycle. PMID:26413406

  10. 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...... 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....... 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...

  11. The emerging phenotype of the testicular carcinoma in situ germ cell

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Bartkova, Jirina; Samson, Michel;

    2003-01-01

    This review summarises the existing knowledge on the phenotype of the carcinoma in situ (CIS) cell. CIS is a common pre-invasive precursor of testicular germ cell tumours of adolescents and young adults. These tumours display a variety of histological forms. Classical seminoma proliferates along...... differentiation and pluripotency, CIS cells found in adult patients seem to be predestined for further malignant progression into one or the other of the two main types of overt tumours. A new concept of phenotypic continuity of differentiation of germ cells along germinal lineage with a gradual loss of embryonic...... that CIS cells originate from primordial germ cells or gonocytes and not from germ cells in the adult testis....

  12. DEFINITION OF A NEW ENTITY OF MALIGNANT EXTRAGONADAL GERM-CELL TUMORS

    NARCIS (Netherlands)

    VANECHTEN, J; DEJONG, B; SINKE, RJ; WEGHUIS, DO; SLEIJFER, DT; OOSTERHUIS, JW

    1995-01-01

    Two malignant extragonadal germ cell tumors are reponed, histologically classified as immature teratomas, having pseudodiploid karyotypes with complex structural rearrangements but lacking isochromosome 12p or other rearrangements involving 12p. The absence of 12p material in structural rearrangemen

  13. Sexual functioning after multimodality treatment for disseminated nonseminomatous testicular germ cell tumor

    NARCIS (Netherlands)

    VanBasten, JP; JonkerPool, G; VanDriel, MF; Sleijfer, DT; Droste, JHJ; VandeWiel, HBM; Molenaar, WM; Hoekstra, HJ; Schraffordt Koops, H.

    1997-01-01

    Purpose: We determined sexual functioning after chemotherapy for disseminated nonseminomatous testicular germ cell tumor, and evaluated the impact of resection of post-chemotherapy residual retroperitoneal tumor. Materials and Methods: A total of 155 consecutive patients treated with chemotherapy fo

  14. Mammalian male germ cells are fertile ground for expression profiling of sexual reproduction.

    Science.gov (United States)

    Wrobel, Gunnar; Primig, Michael

    2005-01-01

    Recent large-scale transcriptional profiling experiments of mammalian spermatogenesis using rodent model systems and different types of microarrays have yielded insight into the expression program of male germ cells. These studies revealed that an astonishingly large number of loci are differentially expressed during spermatogenesis. Among them are several hundred transcripts that appear to be specific for meiotic and post-meiotic germ cells. This group includes many genes that were previously implicated in spermatogenesis and/or fertility and others that are as yet poorly characterized. Profiling experiments thus reveal candidates for regulation of spermatogenesis and fertility as well as targets for innovative contraceptives that act on gene products absent in somatic tissues. In this review, consolidated high density oligonucleotide microarray data from rodent total testis and purified germ cell samples are analyzed and their impact on our understanding of the transcriptional program governing male germ cell differentiation is discussed. PMID:15615893

  15. Radical Resection of a Late-Relapsed Testicular Germ Cell Tumour: Hepatectomy, Cavotomy, and Thrombectomy

    OpenAIRE

    C. Ní Leidhin; Redmond, C. E.; Cahalane, A. M.; Heneghan, H. M.; R. Motyer; Ryan, E. R.; Hoti, E.

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. Thi...

  16. Involvement of epigenetic modifiers in the pathogenesis of testicular dysgenesis and germ cell cancer

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian

    2015-01-01

    cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....

  17. Mouse Germ Cell Development in-vivo and in-vitro

    OpenAIRE

    Deshira Saiti; Orly Lacham-Kaplan

    2007-01-01

    In mammalian development, primordial germ cells (PGCs) represent the initial population of cells that are committed to the germ cell lineage. PGCs segregate early in development, triggered by signals from the extra-embryonic ectoderm. They are distinguished from surrounding cells by their unique gene expression patterns. Some of the more common genes used to identify them are Blimp1, Oct3/4, Fragilis, Stella, c-Kit, Mvh, Dazl and Gcna1. These genes are involved in regulating their migration a...

  18. Clinical and Radiologic Signs of Relapsed Ovarian Germ Cell Tumor: Tissue Is the Issue

    OpenAIRE

    Homs, M Y V; Schreuder, H. W. R.; Jonges, G. N.; Witteveen, P. O.

    2013-01-01

    Malignant ovarian germ cell tumor is a rare disease, but with current treatment strategies including surgery and platinum based chemotherapy survival is excellent. After treatment, intensive followup is indicated to encounter tumor relapse at an early stage. This case describes a 22-year-old female with a history of common variable immune deficiency (CVID) who underwent a resection of a large ovarian germ cell tumor followed by 4 cycles of cisplatin and etoposide resulting in clinical complet...

  19. nanos function is essential for development and regeneration of planarian germ cells

    OpenAIRE

    Wang, Yuying; Zayas, Ricardo M.; Guo, Tingxia; Phillip A Newmark

    2007-01-01

    Germ cells are required for the successful propagation of sexually reproducing species. Understanding the mechanisms by which these cells are specified and how their totipotency is established and maintained has important biomedical and evolutionary implications. Freshwater planarians serve as fascinating models for studying these questions. They can regenerate germ cells from fragments of adult tissues that lack reproductive structures, suggesting that inductive signaling is involved in plan...

  20. Germ Cell Tumor Located in the Midline of the Anterior Neck

    Directory of Open Access Journals (Sweden)

    Tatyana PIRDOPSKA

    2011-09-01

    Full Text Available Primary germ cell tumors involving midline of the anterior neck are extremely rare. Here we report a 68-year-old male who was operated due to a mass lesion in the anterior neck with infiltration of the isthmus of the thyroid gland. Histopathological examination revealed a germ cell tumor with extragonadal localization in the anterior neck infiltrating the isthmus of the thyroid gland.

  1. Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice.

    Science.gov (United States)

    MacLean, Glenn; Li, Hui; Metzger, Daniel; Chambon, Pierre; Petkovich, Martin

    2007-10-01

    Cyp26b1 encodes a retinoic acid (RA) metabolizing cytochrome P450 enzyme that is expressed in embryonic tissues undergoing morphogenesis, including the testes. We have generated transgenic mice lacking Cyp26b1 and have observed increased RA levels in embryonic testes. Cyp26b1(-/-) germ cells prematurely enter meiosis at embryonic d 13.5 and appear to arrest at pachytene stage. Furthermore, after embryonic d 13.5, a rapid increase in apoptosis is observed in male germ cells derived from Cyp26b1(-/-) embryos; germ cells are essentially absent in mutant male neonates. In contrast, testicular somatic cells appear to develop normally in the absence of Cyp26b1. Moreover, ovarian germ and somatic cells appear unaffected by the lack of CYP26B1. We also show that the synthetic retinoid Am580, which is resistant to CYP26 metabolism, induces meiosis of male germ cells in cultured gonads, suggesting that abnormal development of germ cells in the Cyp26b1(-/-) testes results from excess RA rather than the absence of CYP26B1-generated metabolites of RA. These results provide evidence that CYP26B1 maintains low levels of RA in the developing testes that blocks entry into meiosis and acts as a survival factor to prevent apoptosis of male germ cells.

  2. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

    Directory of Open Access Journals (Sweden)

    Koji Komori

    2016-05-01

    Full Text Available A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient’s abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient’s condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.

  3. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

    Science.gov (United States)

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations. PMID:27403124

  4. Primary intracranial germ cell tumor with abnormal high value of alpha-fetoprotein after the radiation therapy. Report of case

    Energy Technology Data Exchange (ETDEWEB)

    Hokin, Kiyohiro; Abe, Hiroshi; Aida, Toshimitsu; Mabuchi, Shouji; Tsuru, Mitsuo; Nakamura, Nishio (Hokkaido Univ., Sapporo (Japan). School of Medicine)

    1983-02-01

    A 7-year-old boy was admitted to Hokkaido University Hospital complaining of headache and vomiting. On admission he was slightly confused and presented Parinaud's sign. CT scan revealed abnormal high density mass with contrast enhancement effect at the pineal region and obstructive hydrocephalus. Laboratory studies showed the normal value of human chorionic gonadotropin and no trace of alphafetoprotein. Germinoma was most suspected based on the findings of CT scan and laboratory studies. The radiation therapy was carried out for a month and CT scan taken after the radiation therapy revealed marked reduction of the size of the tumor at the pineal region, and he was discharged. But he was re-admitted 3 months after the discharge complaining of headache and vomitting again. CT scan showed the recurrence of the tumor and laboratory studies showed abnormal high value of A.F.P. After the ventriculoperitoneal shunt, the sub-occipital craniectomy was performed by the Stein's approach, and the tumor was removed. Pathologically the tumor was a typical yolk sac tumor. This case is a very interesting case because it suggests an alternation of the element of the germ cell tumor by the radiation therapy. At first admission, germinoma was the main element of the tumor judging from the effectiveness of the radiation therapy and laboratory studies. But the main element of the tumor seemed to have changed to yolk sac tumor after the radiation therapy. The relation between the tumor markers and the types of the germ cell tumor and histopathological characters of the intracranial germ cell tumor were discussed.

  5. Amniotic fluid stem cell-based models to study the effects of gene mutations and toxicants on male germ cell formation

    Institute of Scientific and Technical Information of China (English)

    Claudia Gundacker; Helmut Dolznig; Mario Mikula; Margit Rosner; Oliver Brandau; Markus Hengstschl(a)ger

    2012-01-01

    Male infertility is a major public health issue predominantly caused by defects in germ cell development.In the past,studies on the genetic regulation of spermatogenesis as well as on negative environmental impacts have been hampered by the fact that human germ cell development is intractable to direct analysis in vivo.Compared with model organisms including mice,there are fundamental differences in the molecular processes of human germ cell development.Therefore,an in vitro model mimicking human sperm formation would be an extremely valuable research tool.In the recent past,both human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been reported to harbour the potential to differentiate into primordial germ cells and gametes.We here discuss the pessibility to use human amniotic fluid stem (AFS) cells as a biological model.Since their discovery in 2003,AFS cells have been characterized to differentiate into cells of all three germ layers,to be genomically stable,to have a high proliferative potential and to be non-tumourigenic.In addition,AFS cells are not subject of ethical concerns.In contrast to iPS cells,AFSs cells do not need ectopic induction of pluripotency,which is often associated with only imperfectly cleared epigenetic memory of the source cells.Since AFS cells can be derived from amniocentesis with disease-causing mutations and can be transfected with high efficiency,they could be used in probing gene functions for spermatogenesis and in screening for male reproductive toxicity.

  6. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

    NARCIS (Netherlands)

    Krege, S.; Beyer, J.; Souchon, R.; Albers, P.; Albrecht, W.; Algaba, F.; Bamberg, M.; Bodrogi, I.; Bokemeyer, C.; Cavallin-Stahl, E.; Classen, J.; Clemm, C.; Cohn-Cedermark, G.; Culine, S.; Daugaard, G.; Mulder, P.H.M. de; Santis, M. de; Wit, M. de; Wit, R. de; Derigs, H.G.; Dieckmann, K.P.; Dieing, A.; Droz, J.P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S.D.; Muro, X.G. del; Gauler, T.; Geczi, L.; Gerl, A.; Germa-Lluch, J.R.; Gillessen, S.; Hartmann, J.T.; Hartmann, M.; Heidenreich, A.; Hoeltl, W.; Horwich, A.; Huddart, R.; Jewett, M.; Joffe, J.; Jones, W.G.; Kisbenedek, L.; Klepp, O.; Kliesch, S.; Koehrmann, K.U.; Kollmannsberger, C.; Kuczyk, M.; Laguna, P.; Galvis, O.L.; Loy, V.; Mason, M.D.; Mead, G.M.; Mueller, R.; Nichols, C.; Nicolai, N.; Oliver, T.; Ondrus, D.; Oosterhof, G.O.; Ares, L.P.; Pizzocaro, G.; Pont, J.; Pottek, T.; Powles, T.; Rick, O.; Rosti, G.; Salvioni, R.; Scheiderbauer, J.; Schmelz, H.U.; Schmidberger, H.; Schmoll, H.J.; Schrader, M.; Sedlmayer, F.; Skakkebaek, N.E.; Sohaib, A.; Tjulandin, S.; Warde, P.; Weinknecht, S.; Weissbach, L.; Wittekind, C.; Winter, E.; Wood, L.; Maase, H. von der

    2008-01-01

    OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amst

  7. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

    NARCIS (Netherlands)

    Krege, S.; Beyer, J.; Souchon, R.; Albers, P.; Albrecht, W.; Algaba, F.; Bamberg, M.; Bodrogi, I.; Bokemeyer, C.; Cavallin-Stahl, E.; Classen, J.; Clemm, C.; Cohn-Cedermark, G.; Culine, S.; Daugaard, G.; Mulder, P.H.M. de; Santis, M. De; Wit, M. de; Wit, R. de; Derigs, H.G.; Dieckmann, K.P.; Dieing, A.; Droz, J.P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S.D.; Muro, X.G. del; Gauler, T.; Geczi, L.; Gerl, A.; Germa-Lluch, J.R.; Gillessen, S.; Hartmann, J.T.; Hartmann, M.; Heidenreich, A.; Hoeltl, W.; Horwich, A.; Huddart, R.; Jewett, M.; Joffe, J.; Jones, W.G.; Kisbenedek, L.; Klepp, O.; Kliesch, S.; Koehrmann, K.U.; Kollmannsberger, C.; Kuczyk, M.; Laguna, P.; Galvis, O.L.; Loy, V.; Mason, M.D.; Mead, G.M.; Mueller, R.; Nichols, C.; Nicolai, N.; Oliver, T.; Ondrus, D.; Oosterhof, G.O.; Paz-Ares, L.; Pizzocaro, G.; Pont, J.; Pottek, T.; Powles, T.; Rick, O.; Rosti, G.; Salvioni, R.; Scheiderbauer, J.; Schmelz, H.U.; Schmidberger, H.; Schmoll, H.J.; Schrader, M.; Sedlmayer, F.; Skakkebaek, N.E.; Sohaib, A.; Tjulandin, S.; Warde, P.; Weinknecht, S.; Weissbach, L.; Wittekind, C.; Winter, E.; Wood, L.; Maase, H. von der

    2008-01-01

    OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the

  8. Time series analysis supporting the hypothesis that enhanced cosmic radiation during germ cell formation can increase breast cancer mortality in germ cell cohorts

    Science.gov (United States)

    Juckett, D. A.; Rosenberg, Barnett

    Techniques from cancer epidemiology and time series analysis were used to explore the hypothesis that cosmic radiation can induce germ cell changes leading to increases in future breast cancer mortality. A birth cohort time series for female breast cancer mortality was obtained using a model-independent, age-period-cohort analysis on age-specific mortality data for 1940-1990. The birth cohort series contained several oscillatory components, which were isolated and compared to the corresponding frequency components of a cosmic ray surrogate time series - Greenland ice-core 10Be concentrations. A technique, referred to as component wave-train alignment, was used to show that the breast cancer and cosmic ray oscillations were phase-locked approx. 25 years before the time of birth. This is consistent with the time of germ cell formation, which occurs during the fetal development stage of the preceding generation. Evidence is presented that the observable oscillations in the birth cohort series were residues of oscillations of much larger amplitude in the germ cell cohort, which were attenuated by the effect of the broad maternal age distribution. It is predicted that a minimum of 50% of breast cancer risk is associated with germ cell damage by cosmic radiation (priming event), which leads to the development of individuals with a higher risk of breast cancer. It is proposed that the priming event, by preceding other steps of carcinogenesis, works in concert with risk factor exposure during life. The priming event is consistent with epigenetic changes such as imprinting.

  9. Advances in the management of metastatic non-seminomatous germ cell tumours during the cisplatin era: a single-institution experience.

    OpenAIRE

    Gerl, A; Clemm, C.; Schmeller, N.; Hartenstein, R.; Lamerz, R.; Wilmanns, W.

    1996-01-01

    Long-term outcome was reviewed in 266 consecutive patients with metastatic non-seminomatous germ cell tumours treated at a single institution. The overall 3 year survival was 77%, and 3 year progression-free survival was 71%. Multivariate analysis identified the following clinical features as independent prognostic factors: the presence of liver, bone or brain metastasis, serum human chorionic gonadotropin > or = 10000 U l-1 and/or alpha-fetoprotein > or = 1000 ng ml-1, a mediastinal mass > 5...

  10. Deletion of genes implicated in protecting the integrity of male germ cells has differential effects on the incidence of DNA breaks and germ cell loss.

    Directory of Open Access Journals (Sweden)

    Catriona Paul

    Full Text Available BACKGROUND: Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1, MSH2 (MutS homolog 2, involved in mismatch repair pathway, and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage. PRINCIPAL FINDINGS: We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA. CONCLUSIONS: These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility.

  11. Dearth and Delayed Maturation of Testicular Germ Cells in Fanconi Anemia E Mutant Male Mice

    Science.gov (United States)

    Fu, Chun; Begum, Khurshida; Jordan, Philip W.; He, Yan; Overbeek, Paul A.

    2016-01-01

    After using a self-inactivating lentivirus for non-targeted insertional mutagenesis in mice, we identified a transgenic family with a recessive mutation that resulted in reduced fertility in homozygous transgenic mice. The lentiviral integration site was amplified by inverse PCR. Sequencing revealed that integration had occurred in intron 8 of the mouse Fance gene, which encodes the Fanconi anemia E (Fance) protein. Fanconi anemia (FA) proteins play pivotal roles in cellular responses to DNA damage and Fance acts as a molecular bridge between the FA core complex and Fancd2. To investigate the reduced fertility in the mutant males, we analyzed postnatal development of testicular germ cells. At one week after birth, most tubules in the mutant testes contained few or no germ cells. Over the next 2–3 weeks, germ cells accumulated in a limited number of tubules, so that some tubules contained germ cells around the full periphery of the tubule. Once sufficient numbers of germ cells had accumulated, they began to undergo the later stages of spermatogenesis. Immunoassays revealed that the Fancd2 protein accumulated around the periphery of the nucleus in normal developing spermatocytes, but we did not detect a similar localization of Fancd2 in the Fance mutant testes. Our assays indicate that although Fance mutant males are germ cell deficient at birth, the extant germ cells can proliferate and, if they reach a threshold density, can differentiate into mature sperm. Analogous to previous studies of FA genes in mice, our results show that the Fance protein plays an important, but not absolutely essential, role in the initial developmental expansion of the male germ line. PMID:27486799

  12. Brain Metastases in Patients With Germ Cell Tumors: Prognostic Factors and Treatment Options—An Analysis From the Global Germ Cell Cancer Group

    Science.gov (United States)

    Feldman, Darren R.; Lorch, Anja; Kramar, Andrew; Albany, Costantine; Einhorn, Lawrence H.; Giannatempo, Patrizia; Necchi, Andrea; Flechon, Aude; Boyle, Helen; Chung, Peter; Huddart, Robert A.; Bokemeyer, Carsten; Tryakin, Alexey; Sava, Teodoro; Winquist, Eric William; De Giorgi, Ugo; Aparicio, Jorge; Sweeney, Christopher J.; Cohn Cedermark, Gabriella; Powles, Thomas

    2016-01-01

    Purpose To define characteristics, treatment response, and outcomes of men with brain metastases (BM) from germ cell tumors (GCT). Patients and Methods Data from 523 men with BM from GCT were collected retrospectively from 46 centers in 13 countries by using standardized questionnaires. Clinical features were correlated with overall survival (OS) as the primary end point. Results BM were present at initial diagnosis in 228 men (group A) and at relapse in 295 men (group B). OS at 3 years (3-year OS) was superior in group A versus group B (48% v 27%; P < .001). Multiple BM and the presence of liver or bone metastasis were independent adverse prognostic factors in both groups; primary mediastinal nonseminoma (group A) and elevations of α-fetoprotein of 100 ng/mL or greater or of human chorionic gonadotropin of 5,000 U/L or greater (group B) were additional independent adverse prognostic factors. Depending on these factors, the 3-year OS ranged from 0% to 70% in group A and from 6% to 52% in group B. In group A, 99% of patients received chemotherapy; multimodality treatment or high-dose chemotherapy was not associated with statistically improved survival in multivariable analysis. In group B, only 54% of patients received chemotherapy; multimodality treatment was associated with improved survival compared with single-modality therapy (hazard ratio, 0.51; 95% CI, 0.36 to 0.73; P < .001), as was high-dose compared with conventional-dose chemotherapy (hazard ratio, 0.41; 95% CI, 0.24 to 0.70; P = .001). Conclusion Men with BM from GCT have poor OS, particularly if additional risk factors are present. High-dose chemotherapy and multimodality treatment seemed to improve survival probabilities in men with BM at relapse. PMID:26460295

  13. Optimal treatment strategy for intracranial germ cell tumors

    International Nuclear Information System (INIS)

    This study evaluated the long-term outcome of 108 consecutive patients to establish an optimal treatment strategy for respective subgroups of the newly diagnosed intracranial germ cell tumors (GCTs). A retrospective review of medical records from the authors' department for the duration of April 1989 through March 2007 identified 108 patients with newly diagnosed intracranial GCTs. The diagnosis was germinoma in 83 patients, and nongerminomatous GCT (NGGCT) in 25 patients. Long-term quality of life (QOL) was also evaluated in patients with germinoma. Reading patients with germinoma, the 10-year overall and progression-free survival (PFS) rates at a median follow-up period of 99 months were 86 and 74%, respectively. Patients treated with chemotherapy only demonstrated a decline PFS rate, and patients treated with chemotherapy followed by reduced-dose radiation therapy to the whole ventricle, whole brain, or craniospinal axis indicated significantly improved PFS than patients treated with only radiation or reduced-dose radiation therapy to the focal fields. In the QOL study, the academic outcome for germinoma patients appeared to be better than anticipated. However, neurocognitive defunctionalization was observed at the 10-year follow-up for patients treated with whole brain irradiation. Nongerminomatous GCT patients were categorized into good, intermediate, and poor prognosis groups as proposed by the Japanese Pediatric Brain Tumor Study Group. In the good and intermediate prognosis groups, the 10-year overall survived and PFS rates were 100 and 93%, respectively. In the poor prognosis group, the 3-year overall survived and PFS rates were 56 and 29%, respectively. All patients with NGGCTs, in whom the lesions on MR imaging disappeared after combination therapies consisting of resection, radiation therapy, and chemotherapy, remained alive. Chemotherapy followed by reduced-dose radiation therapy covering the whole ventricle improves the prognosis in patients with

  14. Migratory mechanisms of chick primordial germ cells toward gonadal anlage.

    Science.gov (United States)

    Kuwana, T; Rogulska, T

    1999-07-01

    After appearing at the germinal crescent region, chick primordial germ cells (PGCs) migrate toward the presumptive gonads (pG) till stage 19 (Hamburger and Hamilton, 1951). This study seeks to elucidate the roles of passive and active factors in the PGC-migration, physical trapping of circulating PGCs by the capillary network and PGC attraction by chemotactic factor from presumptive gonads. Firstly, latex beads/pollens (the same size or larger than PGCs) were injected into the embryonic bloodstream at stage 13-19 (when PGCs are in the migrating and settlement phase to the presumptive gonad) in ovo in order to determine whether the PGCs passively reach pG. Most of such particles accumulated in the head region (60%), whereas the remainder did the same in the gonadal region (23% at the peak) at stage 16 when both the head and gonadal regions are rich in capillary plexus. After 3 days, most particles in the gonadal region were located at the angles of dorsal mesentery near the developing gonads where many extra-gonadal PGCs had been located, and a few particles were detected close to the gonad. These results suggest that one of the mechanisms of PGC-migration to the developing gonads is an autonomous trapping of PGCs by the capillary network quite close to the germinal epithelium (GE) and passive translocation by morphogenetic movement. Secondly, the attraction for PGCs by the gonadal anlage proper was examined in ovo using chick and quail embryos. Grafts of quail gonadal anlage containing gonadal epithelium and neighbouring mesenchymal tissue were excised from the quail embryo at stages 12 to 16 (staging by Zacchei, 1961). With the aims of eliminating the influence of surrounding tissue, the quail graft was ectopically transplanted into the posterior to the optic vesicle of 8 to 17 somite chick embryo from the point of a posterior region to the auditory vesicle by a fine tungsten needle under the illumination by the method of Hara (1971). Then the region posterior to

  15. Testicular germ cell tumours in dogs are predominantly of spermatocytic seminoma type and are frequently associated with somatic cell tumours

    DEFF Research Database (Denmark)

    Bush, J M; Gardiner, D W; Palmer, J S;

    2011-01-01

    Unlike seminomas in humans, seminomas in animals are not typically sub-classified as classical or spermatocytic types. To compare testicular germ cell tumours (TGCT) in dogs with those of men, archived tissues from 347 cases of canine testicular tumours were morphologically evaluated...... in canine TGCT. None of the canine TGCT evaluated demonstrated the presence of carcinoma in situ cells, a standard feature of human classical seminomas, suggesting that classical seminomas either do not occur in dogs or are rare in occurrence. Canine spermatocytic seminomas may provide a useful model...... and characterized using human classification criteria. Histopathological and immunohistological analysis of PLAP, KIT, DAZ and DMRT1 expression revealed that canine seminomas closely resemble human spermatocytic seminomas. In addition, a relatively frequent concomitant presence of somatic cell tumours was noted...

  16. 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

    ) 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...... 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...

  17. 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

    ) 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 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...

  18. Radiation therapy for intracranial germ cell tumors. Predictive value of tumor response as evaluated by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuhiko; Toita, Takafumi; Kakinohana, Yasumasa; Yamaguchi, Keiichiro; Miyagi, Koichi; Kinjo, Toshihiko; Yamashiro, Katsumi; Sawada, Satoshi [Ryukyu Univ., Nishihara, Okinawa (Japan). School of Medicine

    1997-07-01

    This retrospective study analyzed the outcome in patients with intracranial germ-cell tumors to determine whether tumor response during radiation therapy can predict achievement of primary local with radiation therapy alone. Between 1983 and 1993, 22 patients with untreated primary intracranial germ cell tumors received a total whole brain radiation dose of between 18 Gy and 45 Gy (mean 31.3 Gy) with or without a localized field of 10 to 36.4 Gy (mean, 22.4 Gy), or local irradiation only (1 patient). In 10 patients with pineal tumor only, who were treated first with radiation therapy, tumor response to radiation therapy was evaluated using computed tomography (CT) (at baseline, and approximately 20 Gy and 50 Gy). Areas of calcification in the tumor were subtracted from total tumor volume. Follow-up time ranged from 2 to 12 years. Five-year actuarial survival rates for patients with germinoma were 71%, 100% for patients with a teratoma component, and 100% for patients without histologic verification. Patients with germinomas or tumors suspected of being germinomas who were given more than 50 Gy had no local relapse. There was no correlation between primary local control by radiation therapy alone and initial tumor volume. The rate of tumor volume response to irradiation assessed by CT was significantly different in those patients who relapsed compared to those who did not relapse. Tumor response during radiation therapy using CT was considered to be predictive of primary local control with radiation therapy alone. (author)

  19. Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.

    Directory of Open Access Journals (Sweden)

    Michael K Skinner

    Full Text Available A number of environmental factors (e.g. toxicants have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation progeny in regards to the primordial germ cell (PGC epigenetic reprogramming of the F3 generation (i.e. great-grandchildren. The F3 generation germline transcriptome and epigenome (DNA methylation were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13 and after cord formation in the testis at embryonic day 16 (E16. A larger number of DNA methylation abnormalities (epimutations and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.

  20. Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.

    Science.gov (United States)

    Skinner, Michael K; Guerrero-Bosagna, Carlos; Haque, M; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R

    2013-01-01

    A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided.

  1. Ovarian malignant germ cell tumors: cellular classification and clinical and imaging features.

    Science.gov (United States)

    Shaaban, Akram M; Rezvani, Maryam; Elsayes, Khaled M; Baskin, Henry; Mourad, Amr; Foster, Bryan R; Jarboe, Elke A; Menias, Christine O

    2014-01-01

    Ovarian malignant germ cell tumors (OMGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad. OMGCTs are rare, accounting for about 2.6% of all ovarian malignancies, and typically manifest in adolescence, usually with abdominal pain, a palpable mass, and elevated serum tumor marker levels, which may serve as an adjunct in the initial diagnosis, monitoring during therapy, and posttreatment surveillance. Dysgerminoma, the most common malignant germ cell tumor, usually manifests as a solid mass. Immature teratomas manifest as a solid mass with scattered foci of fat and calcifications. Yolk sac tumors usually manifest as a mixed solid and cystic mass. Capsular rupture or the bright dot sign, a result of increased vascularity and the formation of small vascular aneurysms, may be present. Embryonal carcinomas and polyembryomas rarely manifest in a pure form and are more commonly part of a mixed germ cell tumor. Some OMGCTs have characteristic features that allow a diagnosis to be confidently made, whereas others have nonspecific features, which make them difficult to diagnose. However, imaging features, the patient's age at presentation, and tumor markers may help establish a reasonable differential diagnosis. Malignant ovarian germ cell tumors spread in the same manner as epithelial ovarian neoplasms but are more likely to involve regional lymph nodes. Preoperative imaging may depict local extension, peritoneal disease, and distant metastases. Suspicious areas may be sampled during surgery. Because OMGCTs are almost always unilateral and are chemosensitive, fertility-sparing surgery is the standard of care. PMID:24819795

  2. Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog.

    Science.gov (United States)

    Robinson, Nicholas A; Manivel, J Carlos; Olson, Erik J

    2013-05-01

    Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor. PMID:23604259

  3. Toll-like receptor 11-initiated innate immune response in male mouse germ cells.

    Science.gov (United States)

    Chen, Qiaoyuan; Zhu, Weiwei; Liu, Zhenghui; Yan, Keqin; Zhao, Shutao; Han, Daishu

    2014-02-01

    Toxoplasma gondii and uropathogenic Escherichia coli (UPEC) may infect the testis and impair testicular function. Mechanisms underlying testicular innate immune response to these two pathogens remain to be clarified. The present study examined the function of TLR11, which can be recognized by T. gondii-derived profilin and UPEC, in initiating innate immune response in male mouse germ cells. TLR11 is predominantly expressed in spermatids. Profilin and UPEC induced the expressions of different inflammatory cytokine profiles in the germ cells. In particular, profilin induced the expressions of macrophage chemotactic protein 1 (MCP1), interleukin 12 (IL12), and interferon gamma (IFNG) through nuclear factor KB (NFKB) activation. UPEC induced the expressions of MCP1, IL12, and IFNG, as well as tumor necrosis factor alpha (TNFA), IL6, and IFNB, through the activation of NFKB, IFN regulatory factor 3, and mitogen-activated protein kinases. Evidence showed that profilin induced the innate response in male germ cells through TLR11 signaling, and UPEC triggered the response through TLR11 and other TLR-signaling pathways. We also provided evidence that local injection of profilin or UPEC induces the innate immune response in the germ cells. Data describe TLR11-mediated innate immune function of male germ cells in response to T. gondii profilin and UPEC stimulations. This system may play a role in testicular defense against T. gondii and UPEC infections in mice.

  4. Specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone

    Science.gov (United States)

    Terayama, Hayato; Hirai, Shuichi; Naito, Munekazu; Qu, Ning; Katagiri, Chiaki; Nagahori, Kenta; Hayashi, Shogo; Sasaki, Hiraku; Moriya, Shota; Hiramoto, Masaki; Miyazawa, Keisuke; Hatayama, Naoyuki; Li, Zhong-Lian; Sakabe, Kou; Matsushita, Masayuki; Itoh, Masahiro

    2016-01-01

    There are various autoimmunogenic antigens (AIs) in testicular germ cells (TGCs) recognized as foreign by the body’s immune system. However, there is little information of TGC-specific AIs being available. The aim of this study is to identify TGC-specific AIs. We have previously established that immunization using viable syngeneic TGC can also induce murine experimental autoimmune orchitis (EAO) without using any adjuvant. This study is to identify TGC-specific AIs by TGC liquid chromatography–tandem mass spectrometry analysis, followed by two-dimensional gel electrophoresis that reacted with serum IgG from EAO mice. In this study, we identified 11 TGC-specific AIs that reacted with serum from EAO mice. Real-time RT-PCR analysis showed that the mRNA expressions of seven TGC-specific AIs were significantly higher in only mature testis compared to other organs. Moreover, the recombinant proteins of identified 10 (except unnamed protein) TGC-specific AIs were created by using human embryonic kidney 293 (HEK293) cells and these antigencities were reconfirmed by Western blot using EAO serum reaction. These results indicated Atp6v1a, Hsc70t, Fbp1 and Dazap1 were candidates for TGC-specific AIs. Identification of these AIs will facilitate new approaches for understanding infertility and cancer pathogenesis and may provide a basis for the development of novel therapies. PMID:27752123

  5. Dexamethasone acutely regulates endocrine parameters in stallions and subsequently affects gene expression in testicular germ cells.

    Science.gov (United States)

    Ing, N H; Brinsko, S P; Curley, K O; Forrest, D W; Love, C C; Hinrichs, K; Vogelsang, M M; Varner, D D; Welsh, T H

    2015-01-01

    Testicular steroidogenesis and spermatogenesis are negatively impacted by stress-related hormones such as glucocorticoids. The effects of two injections of a therapeutic dose of dexamethasone (a synthetic glucocorticoid, 0.1mg/kg; i.v.) given 24h apart to each of three stallions were investigated and compared to three saline-injected control stallions. Dexamethasone decreased circulating concentrations of cortisol by 50% at 24h after the initial injection. Serum testosterone decreased by a maximum of 94% from 4 to 20h after the initial injection of dexamethasone. Semen parameters of the dexamethasone-treated stallions were unchanged in the subsequent two weeks. Two weeks after treatment, stallions were castrated. Functional genomic analyses of the testes revealed that, of eight gene products analyzed, dexamethasone depressed concentrations of heat shock protein DNAJC4 and sperm-specific calcium channel CATSPER1 mRNAs by more than 60%. Both genes are expressed in germ cells during spermiogenesis and have been related to male fertility in other species, including humans. This is the first report of decreased DNAJC4 and CATSPER1 mRNA concentrations in testes weeks after dexamethasone treatment. Concentrations of these mRNAs in sperm may be useful as novel markers of fertility in stallions. PMID:25487569

  6. Rapid enlargement of an intracranial germ cell tumor after gonadotropin hormone therapy.

    Science.gov (United States)

    Sasagawa, Yasuo; Tachibana, Osamu; Nakagawa, Athushi; Nakada, Satoko; Nojima, Takayuki; Koya, Daisuke; Iizuka, Hideaki

    2016-09-01

    We report a case of an intracranial germ cell tumor (iGCT) that showed rapid enlargement after human chorionic gonadotropin (hCG) hormone therapy for pituitary hypogonadism. A 16-year-old boy presented with headache and was diagnosed with a suprasellar tumor. He was initially observed without surgery. Intranasal desmopressin therapy was started for central diabetes insipidus, but there was no change in the tumor size on MRI. The diagnosis of the tumor remained unknown for 4years. Levels of serum gonadotropin hormones (follicle-stimulating and luteinizing hormone) and testosterone progressively decreased, and the patient developed pituitary hypogonadism and complained about his undeveloped beard, lack of underarm hair, and erectile dysfunction. Intramuscular gonadotropin injection (hCG 5000U×2/week) was started at age 20. Eight months after the first gonadotropin injection, the MRI showed tumor growth with vivid enhancement. Craniotomy was performed and the tumor was partially resected. The histological diagnosis was immature teratoma. After surgery, the patient was treated with 5 cycles of chemotherapy with carboplatin and etoposide. He also received radiation therapy of 50Gy (20Gy tumor bed and 30Gy whole ventricles) to the residual tumor, after which the tumor decreased in size. We postulate that iGCT may be at risk of progression during hCG hormone therapy. Thus, careful monitoring is required for a patient with iGCT who receives this therapy. PMID:27050912

  7. Effects of relaxin in a co-culture of Sertoli and germ cells.

    Science.gov (United States)

    Pimenta, Maristela T; Porto, Catarina S; Lazari, Maria F M

    2013-01-01

    Spermatogenesis is controlled by FSH, testosterone and paracrine factors produced by Sertoli cells. The knockout of relaxin decreases sperm maturation in mice. Studies from our laboratory have shown that relaxin and its receptor RXFP1 are expressed in rat Sertoli cells, and exogenous relaxin stimulates Sertoli cell proliferation. Relaxin receptors are also detected in the rat germ cells at specific stages of development. Relaxin could therefore affect spermatogenesis either indirectly, by stimulating Sertoli cell proliferation, or directly, by affecting germ cells. The aim of the present study was to explore a role of relaxin at specific stages of spermatogenesis using a co-culture of rat Sertoli and germ cells. Relaxin seems to increase the number of pre-meiotic and meiotic cells. PMID:24640566

  8. Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?

    Directory of Open Access Journals (Sweden)

    John Medwyn Hutson

    2013-01-01

    Full Text Available To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3-9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of CIS and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy

  9. Recent Advances in Application of Male Germ Cell Transplantation in Farm Animals

    Directory of Open Access Journals (Sweden)

    Ali Honaramooz

    2011-01-01

    Full Text Available Transplantation of isolated germ cells from a fertile donor male into the seminiferous tubules of infertile recipients can result in donor-derived sperm production. Therefore, this system represents a major development in the study of spermatogenesis and a unique functional assay to determine the developmental potential and relative abundance of spermatogonial stem cells in a given population of testis cells. The application of this method in farm animals has been the subject of an increasing number of studies, mostly because of its potential as an alternative strategy in producing transgenic livestock with higher efficiency and less time and capital requirement than the current methods. This paper highlights the salient recent research on germ cell transplantation in farm animals. The emphasis is placed on the current status of the technique and examination of ways to increase its efficiency through improved preparation of the recipient animals as well as isolation, purification, preservation, and transgenesis of the donor germ cells.

  10. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    International Nuclear Information System (INIS)

    Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

  11. Tumor germinal no seminomatoso del mediastino con invasión pulmonar Mediastinal non seminomatous germ cell tumor with pulmonary compromise

    Directory of Open Access Journals (Sweden)

    Lucrecia Cúneo

    2008-03-01

    Full Text Available Los tumores germinales extragonadales representan entre el 1 y 2.5% de los tumores de células germinales (TCG, siendo el mediastino la segunda localización en frecuencia luego de las gónadas. Se presenta el caso de un paciente masculino de 29 años de edad que consulta por tos irritativa de cinco meses de evolución. Se realizaron radiografía, tomografía computada (TC y resonancia magnética (RM de tórax y ecografía testicular. Los hallazgos por imágenes, sumados a la presencia de marcadores tumorales elevados (alfa-fetoproteína y gonadotrofina coriónica humana, confirmaron el diagnóstico de TCG extragonadal, avalado posteriormente por la cirugía y la anatomía patológica.The prevalence of extragonadal germ cell tumors is only 1- 2.5% of all germ cell tumors. The mediastinum is the second most common site affected. We present the case of a 29 years old male pacient, with a persistent cough dating back to five months. We performed chest X-R, thorax CT and MRI and testicular US. The findings of this images besides the presence of elevated levels of alpha-fetoprotein and beta-human gonadotropin confirm the diagnosis of extragonadal germ cell tumor.

  12. Radical resection of a late-relapsed testicular germ cell tumour: hepatectomy, cavotomy, and thrombectomy.

    Science.gov (United States)

    Ní Leidhin, C; Redmond, C E; Cahalane, A M; Heneghan, H M; Motyer, R; Ryan, E R; Hoti, E

    2014-01-01

    Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation. PMID:25587480

  13. Radical Resection of a Late-Relapsed Testicular Germ Cell Tumour: Hepatectomy, Cavotomy, and Thrombectomy

    Directory of Open Access Journals (Sweden)

    C. Ní Leidhin

    2014-01-01

    Full Text Available Up to 3.2% of patients with testicular germ cell tumours represent with late-relapsing disease. Aggressive surgical resection confers the greatest chance of cure in this patient group. We present the case of a late and extensively relapsed nonseminomatous germ cell tumour with thrombus present along the entire length of the inferior vena cava, as well as in the right hepatic vein. Techniques practised in liver transplantation were used to achieve complete resection of the tumour thrombus. This case illustrates the enhanced potential for tumour resection through a fusion of principles derived from surgical oncology and liver transplantation.

  14. Examination for intratubular germ cell neoplasia at operation for undescended testis in boys

    DEFF Research Database (Denmark)

    Cortes, D; Thorup, J; Frisch, M;

    1994-01-01

    A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including...... testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia...

  15. Extragonadal germ cell tumor presenting in a woman with systemic lupus erythematosus: a case report

    OpenAIRE

    Yuen Loo C; Mohamad Rozita; Zainudin Soehardy; Halim Abdul; Shahrir Mohd; Saidin Rashidi; Kong Norella

    2010-01-01

    Abstract Introduction Germ cell tumor of the pituitary gland is a very rare occurrence. Case presentation We describe the case of a 28-year-old Malaysian Malay woman with lupus nephritis who complained of a three month headache and blurring of vision. She was found to have a pituitary mass, which was later proven to be a germ cell tumor. As of writing this case report, her disease is in remission. Conclusion The disruption of the pituitary gonad axis could affect the disease activity by reduc...

  16. Extragonadal germ cell tumor presenting in a woman with systemic lupus erythematosus: a case report

    Directory of Open Access Journals (Sweden)

    Yuen Loo C

    2010-03-01

    Full Text Available Abstract Introduction Germ cell tumor of the pituitary gland is a very rare occurrence. Case presentation We describe the case of a 28-year-old Malaysian Malay woman with lupus nephritis who complained of a three month headache and blurring of vision. She was found to have a pituitary mass, which was later proven to be a germ cell tumor. As of writing this case report, her disease is in remission. Conclusion The disruption of the pituitary gonad axis could affect the disease activity by reducing immunoregulatory control.

  17. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  18. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    Energy Technology Data Exchange (ETDEWEB)

    Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  19. Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer

    DEFF Research Database (Denmark)

    Lajer, Henrik; Daugaard, Gedske; Andersson, Anna-Maria;

    2002-01-01

    : Group 1, 34 patients with disseminated disease (24 nonseminomatous germ cell tumors [NSGCT] and 10 seminomatous germ cell tumors [SGCT]); this group of patients were followed during the course of chemotherapy with measurements of TRA-1-60, HCG and AFP; Group 2, 28 patients with Stage I NSGCT (22 with...

  20. File list: NoD.Gon.20.AllAg.Testicular_germ_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Gon.20.AllAg.Testicular_germ_cells mm9 No description Gonad Testicular germ cel...ls http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Gon.20.AllAg.Testicular_germ_cells.bed ...

  1. [Therapy-Related Acute Myeloid Leukemia Following Etoposide Based Chemotherapy in Germ Cell Tumor].

    Science.gov (United States)

    Okumura, Yoshinaga; Oae, Masashi; Shiraishi, Yusuke; Soda, Takeshi; Kanamaru, Hiroshi; Arima, Nobuyoshi

    2016-05-01

    A 27-year-old man visited our hospital with painless swelling of the left scrotum. Hematologic studies showed the following levels of lactate dehydrogenase, 3,171 IU/l ; alpha-fetoprotein, 2.2 ng/ml ; and β- human chorionic gonadotropin, 0.4 ng/ml, and abdominal computed tomography revealed a mass of 10×8 ×4 cm in the left testis, and that of 3.5×3.0×5.0 cm in the left renal hilar lymph node, without any other metastasis. Left high inguinal orchiectomy was performed, and histopathological examination revealed mixed form with seminoma and teratoma. He was diagnosed to have a left germ cell tumor with left renal hilar lymph node metastases, pT1, N3, M0, stage II C, indicating poor prognosis with IGCCC. The patient received four cycles of chemotherapy, COMPE regimen (CDDP, VCR, MTX, PEP, VP-16 [etoposide]). After lactate dehydrogenase, alpha-fetoprotein, and β -human chorionic gonadotropin all normalized, retroperitoneal lymph node dissection was performed. Histopathological examination revealed only a mature teratoma. Two and half years later, hematologic studies showed blast transformation. Bone marrow biopsy revealed acute myeloblastic lymphoma (M2). The patient received one cycle of AraC and daunorubicin, one cycle of high dose AraC, and three cycles of AraC and mitoxantrone. After chemotherapy, he has maintained a disease-free status for 11 years. In this case, etoposide, a topoisomerase II inhibitor, was the presumed cause of therapy-related acute myeloid leukemia. After administering chemotherapeutic agents especially etoposide, it is important to check blood count periodically for a long time. PMID:27320120

  2. Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Jørgensen, N; Müller, Jørn;

    1996-01-01

    conditions which included 45,X/46,XY mosaicism; androgen insensitivity syndrome; and 46,XY/iso(p)Y mosaicism. Individuals with such disorders of sexual differentiation and Y-chromosome material carry a very high risk of developing testicular neoplasms. Fetal testicular germ cells of the intersex subjects...

  3. Safety and efficacy of resistance training in germ cell cancer patients undergoing chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Jones, L W; Tolver, Anders;

    2014-01-01

    Abstract Background: Bleomycin–etoposid–cisplatin (BEP) chemotherapy is curative in most patients with disseminated germ cell cancer (GCC) but also associated with toxic actions and dysfunction in non-targeted tissues. We investigated changes in muscle function during BEP and the safety...

  4. Comparative genomic and in situ hybridization of germ cell tumors of the infantile testis

    NARCIS (Netherlands)

    Mostert, M; Rosenberg, C; Stoop, H; Schuyer, M; Timmer, A; Oosterhuis, W; Looijenga, L

    2000-01-01

    Chromosomal information on germ cell tumors of the infantile testis, ie, teratomas and yolk sac tumors, is limited and controversial. We studied two teratomas and four yolk sac tumors using comparative genomic hybridization (CGH) and in situ hybridization. No chromosomal anomalies were found in the

  5. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    Energy Technology Data Exchange (ETDEWEB)

    Selle, F.; Gligorov, J. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France); Richard, S.; Khalil, A. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Alexandre, I. [Medical Oncology Department, Hospital Centre of Bligny, Briis-sous-Forges (France); Avenin, D.; Provent, S.; Soares, D.G. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Lotz, J.P. [Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance Hospitals of Paris, Alliance for Cancer Research (APREC), Paris (France); Pierre & Marie Curie University (UPMC Paris VI), Paris (France)

    2014-11-04

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

  6. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice

    Science.gov (United States)

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

  7. DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells

    Directory of Open Access Journals (Sweden)

    Hsu-Hsin Chen

    2014-11-01

    Full Text Available The scarcity of primordial germ cells (PGCs in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

  8. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    International Nuclear Information System (INIS)

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis

  9. Superior Vena Cava Syndrome: A Presenting Feature of Mediastinal Germ Cell Tumor

    Directory of Open Access Journals (Sweden)

    Mahua Roy

    2010-04-01

    Full Text Available Superior vena cava syndrome (SVCS is rare in children. Non-Hodgkin’s Lymphoma (NHL is the most common cause of SVCS in children. This report an adolescent male who presented with SVCS due to mixed germ cell tumor (GCT of the anterior mediastinum with predominant yolk cell component. Such etiology of SVCS is rarely reported.

  10. Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes

    DEFF Research Database (Denmark)

    Rajpert-De Meyts, Ewa; Jørgensen, N; Müller, Jørn;

    1996-01-01

    Stem cell factor (SCF) and its receptor Kit encoded by the c-kit proto-oncogene are crucial for the development and migration of primordial germ cells in rodents. The expression of Kit has been examined immunohistochemically in gonads obtained from five specimens of fetal tissues with intersex co...

  11. Temporal germ cell development strategy during continuous spermatogenesis within the montane lizard, Sceloporus bicanthalis (Squamata; Phrynosomatidae).

    Science.gov (United States)

    Gribbins, Kevin; Anzalone, Marla; Collier, Matthew; Granados-González, Gisela; Villagrán-Santa Cruz, Maricela; Hernández-Gallegos, Oswaldo

    2011-10-01

    Sceloporus bicanthalis is a viviparous lizard that lives at higher elevations in Mexico. Adult male S. bicanthalis were collected (n = 36) from the Nevado de Toluca, Mexico (elevation is 4200 m) during August to December, 2007 and January to July, 2008. Testes were extracted, fixed in Trumps, and dehydrated in a graded series of ethanol. Tissues were embedded, sectioned (2 μm), stained, and examined via a light microscope to determine the spermatogenic developmental strategy of S. bicanthalis. In all months examined, the testes were spermiogenically active; based on this, plus the presence of sperm in the lumina of seminiferous tubules, we inferred that S. bicanthalis had year-round or continuous spermatogenesis, unlike most reptiles that occupy a temperate or montane habitat. It was recently reported that seasonally breeding reptiles had a temporal germ cell development strategy similar to amphibians, where germ cells progress through spermatogenesis as a single population, which leads to a single spermiation event. This was much different than spatial development within the testis of other derived amniotes. We hypothesized that germ cell development was temporal in S. bicanthalis. Therefore, we wanted to determine whether reptiles that practice continuous spermatogenesis have a mammalian-like spatial germ cell development, which is different than the typical temperate reptile exhibiting a temporal development. In the present study, S. bicanthalis had a temporal development strategy, despite its continuous spermatogenic cycle, making them similar to tropical anoles.

  12. Etiology and early pathogenesis of malignant testicular germ cell tumors: Towards possibilities for preinvasive diagnosis

    NARCIS (Netherlands)

    J.E. Elzinga-Tinke; G.R. Dohle (Gert); L.H.J. Looijenga (Leendert)

    2015-01-01

    textabstractMalignant testicular germ cell tumors (TGCT) are the most frequent cancers in Caucasian males (20-40 years) with an 70% increasing incidence the last 20 years, probably due to combined action of (epi)genetic and (micro)environmental factors. It is expected that TGCT have carcinoma in sit

  13. TOPAZ1, a novel germ cell-specific expressed gene conserved during evolution across vertebrates.

    Directory of Open Access Journals (Sweden)

    Adrienne Baillet

    Full Text Available BACKGROUND: We had previously reported that the Suppression Subtractive Hybridization (SSH approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene. PRINCIPAL FINDINGS: Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons, respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. CONCLUSIONS: We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line.

  14. Functional Genomics of Germ Cell Tumors: from balls to bytes and back again

    NARCIS (Netherlands)

    M.A. Rijlaarsdam (Martin)

    2014-01-01

    markdownabstract__Abstract__ The work discussed in this thesis explains the role of the functional genome in germ cell tumor (GCT) pathogenesis by applying newly developed and existing computational methods to (genome-wide) functional genomic datasets. Specifically, epigenetic and (post-)transcript

  15. The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice.

    Science.gov (United States)

    Hou, Siyuan; Xian, Li; Shi, Peiliang; Li, Chaojun; Lin, Zhaoyu; Gao, Xiang

    2016-01-01

    While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress. PMID:27226137

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

    Directory of Open Access Journals (Sweden)

    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.

  17. The attractive Achilles heel of germ cell tumours : an inherent sensitivity to apoptosis-inducing stimuli

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Vellenga, E; de Jong, S

    2003-01-01

    Testicular germ cell tumours (TGCTs) are extremely sensitive to cisplatin-containing chemotherapy. The rapid time course of apoptosis induction after exposure to cisplatin suggests that TGCT cells are primed to undergo programmed cell death as an inherent property of the cell of origin. In fact, apo

  18. A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies.

    Science.gov (United States)

    Schaner, Christine E; Deshpande, Girish; Schedl, Paul D; Kelly, William G

    2003-11-01

    In C. elegans, mRNA production is initially repressed in the embryonic germline by a protein unique to C. elegans germ cells, PIE-1. PIE-1 is degraded upon the birth of the germ cell precursors, Z2 and Z3. We have identified a chromatin-based mechanism that succeeds PIE-1 repression in these cells. A subset of nucleosomal histone modifications, methylated lysine 4 on histone H3 (H3meK4) and acetylated lysine 8 on histone H4 (H4acetylK8), are globally lost and the DNA appears more condensed. This coincides with PIE-1 degradation and requires that germline identity is not disrupted. Drosophila pole cell chromatin also lacks H3meK4, indicating that a unique chromatin architecture is a conserved feature of embryonic germ cells. Regulation of the germline-specific chromatin architecture requires functional nanos activity in both organisms. These results indicate that genome-wide repression via a nanos-regulated, germ cell-specific chromatin organization is a conserved feature of germline maintenance during embryogenesis.

  19. Superior Vena Cava Syndrome: A Presenting Feature of Mediastinal Germ Cell Tumor

    OpenAIRE

    Mahua Roy; Rajat Bandyopadhyay; Narayan Pandit; Soumita Sengupta

    2010-01-01

    Superior vena cava syndrome (SVCS) is rare in children. Non-Hodgkin’s Lymphoma (NHL) is the most common cause of SVCS in children. This report an adolescent male who presented with SVCS due to mixed germ cell tumor (GCT) of the anterior mediastinum with predominant yolk cell component. Such etiology of SVCS is rarely reported.

  20. Exposure to endocrine disruptor induces transgenerational epigenetic deregulation of microRNAs in primordial germ cells.

    Directory of Open Access Journals (Sweden)

    Miguel A Brieño-Enríquez

    Full Text Available In mammals, germ cell differentiation is initiated in the Primordial Germ Cells (PGCs during fetal development. Prenatal exposure to environmental toxicants such as endocrine disruptors may alter PGC differentiation, development of the male germline and induce transgenerational epigenetic disorders. The anti-androgenic compound vinclozolin represents a paradigmatic example of molecule causing transgenerational effects on germ cells. We performed prenatal exposure to vinclozolin in mice and analyzed the phenotypic and molecular changes in three successive generations. A reduction in the number of embryonic PGCs and increased rate of apoptotic cells along with decrease of fertility rate in adult males were observed in F1 to F3 generations. Blimp1 is a crucial regulator of PGC differentiation. We show that prenatal exposure to vinclozolin deregulates specific microRNAs in PGCs, such as miR-23b and miR-21, inducing disequilibrium in the Lin28/let-7/Blimp1 pathway in three successive generations of males. As determined by global maps of cytosine methylation, we found no evidence for prominent changes in DNA methylation in PGCs or mature sperm. Our data suggest that embryonic exposure to environmental endocrine disruptors induces transgenerational epigenetic deregulation of expression of microRNAs affecting key regulatory pathways of germ cells differentiation.

  1. Germ cell development in larval and juvenile carp (Cyprinus carpio L.).

    NARCIS (Netherlands)

    Winkoop, van A.

    1995-01-01

    This thesis describes the development of larval and juvenile gonads of a teleost fish, the common carp, with special attention to the differentiation of the primordial germ cells. The early gonadal development has received relatively little attention, hitherto, as the research on fish reproduction h

  2. The developmental fate of green fluorescent mouse embryonic germ cells in chimeric embryos

    Institute of Scientific and Technical Information of China (English)

    XUXIN; SUMIOSUGANO; 等

    1999-01-01

    Primordial germ cells (PGCs),as precursors of mammalian germ lineage,have been gaining more attention as a new resource of pluripotent stem cells,which bring a great possibility to study developmental events of germ cell in vitro and at animal level.EG4 cells derived from 10.5 days post coitum (dpc) PGCs of 129/svJ strain mouse were established and maintained in an undifferentiated state.With an attempt to study the differentiation capability of EG4 cells with a reporter protein:green fluorescence protein,and the possible application of EG4 cells in the research of germ cell development,we have generated several EG4-GFP cell lines expressing enhanced green fluorescence protein (EGFP) and still maintaining typical characteristics of pluripotent stem cells.Then,the differentiation of EG4-GFP cells in vitro as well as their developmental fate in chimeric embryos which were produced by aggregating EG4-GFP cells to 8-cell stage embryos were studied.The results showed that EG4 cells carrying green fluorescence have a potential use in the research of germ cell development and other related studies.

  3. Germ cell development in the scleractinian coral Euphyllia ancora (Cnidaria, Anthozoa.

    Directory of Open Access Journals (Sweden)

    Shinya Shikina

    Full Text Available Sexual reproduction of scleractinian coral is among the most important means of establishing coral populations. However, thus far, little is known about the mechanisms underlying coral gametogenesis. To better understand coral germ cell development, we performed a histological analysis of gametogenesis in Euphyllia ancora and characterized the coral homolog of the Drosophila germline marker gene vasa. The histological analysis revealed that E. ancora gametogenesis occurs in the mesenterial mesoglea between the mesenterial filaments and the retractor muscle bands. The development of germ cells takes approximately one year in females and half a year in males. Staining of tissue sections with an antibody against E. ancora Vasa (Eavas revealed anti-Eavas immunoreactivity in the oogonia, early oocyte, and developing oocyte, but only faint or undetectable reactivity in developing oocytes that were >150 µm in diameters. In males, Eavas could be detected in the spermatogonia and primary spermatocytes but was only faintly detectable in the secondary spermatocytes, spermatids, and sperms. Furthermore, a reverse transcription-polymerase chain reaction analysis and Western blotting analysis of unfertilized mature eggs proved the presence of Eavas transcripts and proteins, suggesting that Eavas may be a maternal factor. Vasa may represent a germ cell marker for corals, and would allow us to distinguish germ cells from somatic cells in coral bodies that have no distinct organs.

  4. Impaired germ cell development due to compromised cell cycle progression in Skp2-deficient mice

    Directory of Open Access Journals (Sweden)

    Nakayama Keiko

    2006-04-01

    Full Text Available Abstract Background The gonads are responsible for the production of germ cells through both mitosis and meiosis. Skp2 is the receptor subunit of an SCF-type ubiquitin ligase and is a major regulator of the progression of cells into S phase of the cell cycle, which it promotes by mediating the ubiquitin-dependent degradation of p27, an inhibitor of cell proliferation. However, the role of the Skp2-p27 pathway in germ cell development remains elusive. Results We now show that disruption of Skp2 in mice results in a marked impairment in the fertility of males, with the phenotypes resembling Sertoli cell-only syndrome in men. Testes of Skp2-/- mice manifested pronounced germ cell hypoplasia accompanied by massive apoptosis in spermatogenic cells. Flow cytometry revealed an increased prevalence of polyploidy in spermatozoa, suggesting that the aneuploidy of these cells is responsible for the induction of apoptosis. Disruption of the p27 gene of Skp2-/- mice restored germ cell development, indicating that the testicular hypoplasia of Skp2-/- animals is attributable to the antiproliferative effect of p27 accumulation. Conclusion Our results thus suggest that compromised cell cycle progression caused by the accumulation of p27 results in aneuploidy and the induction of apoptosis in gonadal cells of Skp2-/- mice. The consequent reduction in the number of mature gametes accounts for the decreased fertility of these animals. These findings reinforce the importance of the Skp2-p27 pathway in cell cycle regulation and in germ cell development.

  5. Fluorodeoxyglucose positron emission tomography in the initial staging of germ cell tumours

    Energy Technology Data Exchange (ETDEWEB)

    Hain, S.F.; O' Doherty, M.J. [Clinical PET Centre, Guy' s and St Thomas' Hospitals, London (United Kingdom); Timothy, A.R.; Leslie, M.D.; Partridge, S.E. [Dept. of Clinical Oncology, Guy' s and St Thomas' Hospitals, London (United Kingdom); Huddart, R.A. [Dept. of Radiotherapy and Oncology, Royal Marsden, Surrey (United Kingdom)

    2000-05-01

    Testicular cancer is a rare tumour with the potential for cure at diagnosis. It is important, however, to identify those patients with metastases at presentation so as to ensure that the optimum treatment strategy is employed. Many criteria have been used to try to place patients into high- or low-risk groups, with variable success. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has the potential to identify active disease and thereby influence further management. Here we report on a retrospective study of the use of FDG-PET in the detection of metastatic testicular carcinoma at diagnosis. Thirty-one patients [13 with seminoma and 18 with non-seminomatous germ cell tumours (13 teratomas, 5 mixed)] were staged by FDG-PET scanning. The imaging was performed using a Siemens ECAT 951 scanner. All results were assessed on the basis of histology or clinical follow-up. FDG-PET scan identified metastatic disease in ten and was negative in 16; there were no false-positives and five false-negatives. There were six patients in whom FDG-PET was negative and computed tomography was regarded as suspicious but follow-up was inconclusive. The positive predictive value was 100%. The negative predictive value was 76% or 91%, depending on whether the aforementioned six cases were regarded as true-negatives or false-negatives. It may be concluded that FDG-PET is capable of detecting metastatic disease at diagnosis that is not identified by other imaging techniques. These preliminary results are sufficient to suggest that a large prospective study should be performed to evaluate the role of FDG-PET in primary staging of disease. (orig.)

  6. Chicken stem cell factor enhances primordial germ cell proliferation cooperatively with fibroblast growth factor 2.

    Science.gov (United States)

    Miyahara, Daichi; Oishi, Isao; Makino, Ryuichi; Kurumisawa, Nozomi; Nakaya, Ryuma; Ono, Tamao; Kagami, Hiroshi; Tagami, Takahiro

    2016-04-22

    An in vitro culture system of chicken primordial germ cells (PGCs) has been recently developed, but the growth factor involved in the proliferation of PGCs is largely unknown. In the present study, we investigated the growth effects of chicken stem cell factor (chSCF) on the in vitro proliferation of chicken PGCs. We established two feeder cell lines (buffalo rat liver cells; BRL cells) that stably express the putative secreted form of chSCF (chSCF1-BRL) and membrane bound form of chSCF (chSCF2-BRL). Cultured PGC lines were incubated on chSCF1 or chSCF2-BRL feeder cells with fibroblast growth factor 2 (FGF2), and growth effects of each chSCF isoform were investigated. The in vitro proliferation rate of the PGCs cultured on chSCF2-BRL at 20 days of culture was more than threefold higher than those cultured on chSCF1-BRL cells and more than fivefold higher than those cultured on normal BRL cells. Thus, use of chSCF2-BRL feeder layer was effective for in vitro proliferation of chicken PGCs. However, the acceleration of PGC proliferation on chSCF2-BRL was not observed without FGF2, suggesting that chSCF2 would act as a proliferation co-factor of FGF2. We transferred the PGCs cultured on chSCF2-BRL cells to recipient embryos, generated germline chimeric chickens and assessed the germline competency of cultured PGCs by progeny test. Donor-derived progenies were obtained, and the frequency of germline transmission was 3.39%. The results of this study demonstrate that chSCF2 induces hyperproliferation of chicken PGCs retaining germline competency in vitro in cooperation with FGF2. PMID:26727404

  7. Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases.

    Science.gov (United States)

    Balzer, Bonnie L; Ulbright, Thomas M

    2006-07-01

    Spontaneous regression of testicular germ cell tumors (GCTs) is a well-recognized phenomenon but has been incompletely characterized. Many pathologists are not familiar with the findings that support a diagnosis of a "burnt-out" primary in a patient with metastatic GCT. We therefore report the clinical, gross, and histologic findings in 42 cases of testicular GCT that showed either complete (26) or greater than 50% scarring (16). Thirty-seven patients (88%) had either known GCT metastasis or some residual testicular GCT, and none had treatment before orchiectomy. The patients were 17 to 67 years old, with a median of 32. Thirty presented with symptoms of metastasis, 7 with a testicular mass, 2 with elevated human chronic gonadotropin, and 1 with testicular pain. In 2 patients the presentation was unknown. Two patients had prior orchiopexy; another had an intraabdominal testis, and 2 others had prior contralateral seminoma (20 and 42 years previously). Gross descriptions in 37 cases identified white to tan scars, 0.6 to 2.4 cm, in 33. These were circumscribed in 16, with 15 of these having nodular or multinodular configurations and 1 a band-like appearance. In 9 cases the scar was ill defined or stellate, and in 8 cases no further details concerning the scar configuration were available. In 4 cases no scar was apparent; 2 of these had received intraoperative biopsy. Microscopically, all cases showed circumscribed to irregular foci of scarring, distinct from the adjacent parenchyma, in association with widespread testicular atrophy. Other common features were lymphoplasmacytic infiltrates in the scars (37/42) and "ghost" tubules in scars (31/42). Less common features in the scars included angiomatous foci (22/42), siderophages (15/42), and coarse intratubular calcifications (6/42); in the surrounding testis they included intratubular germ cell neoplasia, unclassified (IGCNU) (22/42), Leydig cell prominence (18/42), and necrosis (5/42). Tubular microliths occurred in

  8. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer;

    2007-01-01

    and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The first part of the consensus paper describes the clinical...... in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer...

  9. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II

    DEFF Research Database (Denmark)

    Krege, Susanne; Beyer, Jörg; Souchon, Rainer;

    2007-01-01

    guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised...... trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged Udgivelsesdato: 2008/3...

  10. Evaluation of SF-1 expression in testicular germ cell tumors: a tissue microarray study of 127 cases.

    Science.gov (United States)

    Sangoi, Ankur R; McKenney, Jesse K; Brooks, James D; Higgins, John P

    2013-07-01

    Differentiating testicular germ cell tumors from sex-cord stromal tumors can be difficult in certain cases because of overlapping morphologic features and/or an absence of clinically apparent hormonal symptoms. Immunohistochemistry may be needed as an ancillary diagnostic tool in this differential diagnostic setting. Steroidogenic factor-1 (SF-1) is a nuclear transcription factor controlling steroidogenesis and is expressed in developing Sertoli and Leydig cells. Although 1 recent study has reported SF-1 nuclear immunoreactivity in testicular sex-cord stromal tumors, the specificity for this marker in germ cell tumors has not been evaluated. After encountering several problematic cases (including some on testicular biopsy), we sought to determine the diagnostic specificity of SF-1 in a large series of germ cell tumors. Nuclear immunohistochemical expression of SF-1 was evaluated in 127 germ cell tumors using tissue microarray technology with 23 non-germ cell tumor tissues as positive internal controls. No nuclear SF-1 expression was identified in any of the 127 germ cell tumors [including choriocarcinoma (3), embryonal carcinoma (25), epidermal inclusion cyst (1), intratubular germ cell neoplasia unclassified (4), seminoma (72), spermatocytic seminoma (2), teratoma (8), and yolk sac tumor (12)]. All 23 non-germ cell tumor tissues showed strong nuclear SF-1 expression in Sertoli and/or Leydig cells [including testicular atrophy (10), cryptorchidism (2), normal testis (4), hypospermatogenesis (1), immature testis (1), intratubular large cell calcifying Sertoli cell tumor (1), Leydig cell tumor (3), and Sertoli only (1)]. This study documents the absence of SF-1 expression in testicular germ cell tumors and supports its specificity for sex-cord stromal lesions in this diagnostic context.

  11. Effect of prolonged cryptorchidism on germ cell apoptosis and testicular sperm count

    Institute of Scientific and Technical Information of China (English)

    AlbahaBarqawi; HeraldTrummer; RandallMeacham

    2004-01-01

    Aim:To evaluate the long term effect of experimental cryptorchidism on germ cell apoptotic rate and testicular sperm content in adult rats.Methods:Bilateral cryptorchidism was created in 40 adult male Sprague-Dawley rats by surgically manipulating the testes into the abdominal cavity and closing the internal inguinal ring.The rats were sacrificed and the testes removed 6 hours and 2,4,7,21,28 and 56 days after cryptorchidism.Germ cell apoptosis was quantified by means of TUNEL assay and apoptosis was confirmed using transmission electron microscopy.Results:The rate of apoptosis peaked at 4 days of cryptorchidism and then progressively declined to a nadir at 14 days of cryptorchidism.At 56 days of cryptorchidism,the germinal epithelium was largely depleted by the apoptotic process and only a few mature sperm were seen within the testis.At this point,a few tubules were seen to be repopulating with primary spermatocytes and the level of germ cell apoptosis began to increase marginally.Testicular sperm count (TSC) began to decline rapidly at day 7 of cryptorchidism.Only a few mature sperm were found in the testes of rats following 56 days of cryptorchidism.Multinucleated giant cells (MGC) were most numerous within the seminiferous tubules at day 4.At day 7,35% of MGCs were TUNEL positive.At all subsequent time points,however,MGCs fail to stain positive for apoptosis.This resumption of increased apoptosis coincided with the appearance of a population of primary spermatocytes in some seminiferous tubules.Moreover,there was not a corresponding increase in the number of mature sperm after 56 days of cryptorchidism.Conclusion:The decline in germ cell apoptosis after 4 days of cryptorchidism can be attributed to be the result of an overall depletion of germ cells.It appears that after a prolonged cryptorchidism (56 days),there is a limited resumption of spermatogenesis presumably as a result of a decrease in the maturing germ cells undergoing programmed cell death

  12. Interspecific comparison of the effects of continuous ionizing radiation on the primitive mammalian stem germ cell

    International Nuclear Information System (INIS)

    The response of the mammalian oocyte to radiation is characterized by wide interspecific differences, and results of preliminary assays suggest that this may be the case with the primitive stem germ cell. To test the validity of this observation and to define probable causes for the differences, prenatal mice, rats, and guinea pigs were irradiated continuously throughout gestation at rates of 1 and 3 rads per 23-hr day. Prenatal pigs were irradiated continuously for 108 days at a dose rate of 0.25 rad per 23-hr day. In all cases germ cells were enumerated in gonads excised either at birth or 6 days after birth. A dose rate of 0.25 rad/day reduced the germ-cell number in the male and female pig to 38 and 60% of control, respectively, and only 1 and 5% of the germ cells in the respective sexes survived a dose rate of 1 rad/day. Application of the single-hit multitarget model to all pig data yielded values for D0 and n of 28 and 0.8, respectively, for the male and 27 and 3.2, respectively, for the female. Corresponding values for the male and female rat were 275 (D0) and 0.3 (n) and 159 (D0) and 0.8 (n), respectively. Both sexes of the pig were either sterilized or brought near sterility by a dose rate of 1 rad/day. In the case of the male rodent, however, this dose rate reduced germ-cell number to only 71% of control in the mouse, 50% of control in the rat, and 41% of control in the guinea pig. Ninety percent of the germ cells in the female rat survived a dose rate of 1 rad/day, as did 87% in the mouse and 71% in the guinea pig. When total dose was used as the basis of comparison, the pig remained the most sensitive species. Thus the differences among rodent species are not great when compared to the tremendous difference between the rodent and pig. When rodents are compared with pigs, the difference in the magnitude of the effect of continuous irradiation on the primitive stem cells of both sexes appears to be dependent on length of time at risk

  13. Male germ cell-specific knockout of cholesterogenic cytochrome P450 lanosterol 14α-demethylase (Cyp51)[S

    OpenAIRE

    Keber, Rok; Ačimovič, Jure; Majdič, Gregor; Motaln, Helena; Rozman, Damjana; Horvat, Simon

    2013-01-01

    Cytochrome P450 lanosterol 14α-demethylase (CYP51) and its products, meiosis-activating sterols (MASs), were hypothesized by previous in vitro studies to have an important role in regulating meiosis and reproduction. To test this in vivo, we generated a conditional male germ cell-specific knockout of the gene Cyp51 in the mouse. High excision efficiency of Cyp51 allele in germ cells resulted in 85–89% downregulation of Cyp51 mRNA and protein levels in germ cells. Quantitative metabolic profil...

  14. Metabolomic Response of Human Embryonic Stem Cell Derived Germ-like Cells after Exposure to Steroid Hormones

    Science.gov (United States)

    To assess the potential risks of human exposure to endocrine active compounds (EACs), the mechanisms of toxicity must first be identified and characterized. Currently, there are no robust in vitro models for identifying the mechanisms of toxicity in germ cells resulting from EAC ...

  15. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    DEFF Research Database (Denmark)

    Brokken, Leon J S; Lundberg-Giwercman, Yvonne; Rajpert-De Meyts, Ewa;

    2013-01-01

    In the Western world, testicular germ cell cancer (TGCC) is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing...... receptor (AHR). AHR signaling pathway is known to interfere with reproductive hormone signaling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well...... supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action....

  16. Early Depletion of Primordial Germ Cells in Zebrafish Promotes Testis Formation

    Directory of Open Access Journals (Sweden)

    Keh-Weei Tzung

    2015-01-01

    Full Text Available As complete absence of germ cells leads to sterile males in zebrafish, we explored the relationship between primordial germ cell (PGC number and sexual development. Our results revealed dimorphic proliferation of PGCs in the early zebrafish larvae, marking the beginning of sexual differentiation. We applied morpholino-based gene knockdown and cell transplantation strategies to demonstrate that a threshold number of PGCs is required for the stability of ovarian fate. Using histology and transcriptomic analyses, we determined that zebrafish gonads are in a meiotic ovarian stage at 14 days postfertilization and identified signaling pathways supporting meiotic oocyte differentiation and eventual female fate. The development of PGC-depleted gonads appears to be restrained and delayed, suggesting that PGC number may directly regulate the variability and length of gonadal transformation and testicular differentiation in zebrafish. We propose that gonadal transformation may function as a developmental buffering mechanism to ensure the reproductive outcome.

  17. Primordial germ cell biology at the beginning of the XXI century.

    Science.gov (United States)

    De Felici, Massimo

    2009-01-01

    At the XIV Workshop on the Development and Function of the Reproductive Organs held at the Congress Centre of the University of Rome Tor Vergata, Monteporzio Catone, Rome, Italy, the introduction to the first session entitled Mammalian primordial germ cells dedicated to the memory of Anne McLaren, was the occasion for a concise review of the state of art of research on the biology of primordial germ cells (PGCs). This great, unforgettable scientist, who died in a car accident in July 2007, dedicated most of her studies to this field over the last 25 years. Topics briefly reviewed in this Meeting Report are: 1) how the germ line is determined; 2) what are the mechanisms underlying PGC migration; 3) to what extent PGC survival, proliferation and differentiation are cell autonomous or environmentally controlled processes and 4) how the potential for totipotency is retained in PGCs.

  18. A transplant recipient with a mixed germ-cell ovarian tumor

    Directory of Open Access Journals (Sweden)

    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  19. "MAXIMAL FERTILITY SPARING SURGERY IN A PATIENT WITH A RARE MIXED GERM CELL TUMOR"

    Directory of Open Access Journals (Sweden)

    F. Ghaemmaghami

    2004-10-01

    Full Text Available Ovarian mixed germ cell tumors consisting of endodermal sinus tumor and immature teratoma are very rare and have been reported only in a few case reports. Here we report a rare mixed germ cell tumor of ovary which was consisted of endodermal sinus tumor and immature teratoma components with an unusual intraabdominal location. Patient was a 21 years old girl with the chief compliant of abdominal pain. Ultrasound and CT scan showed a lobulated cystic mass. Laparotomy was performed and due to unusual localization, in which tumor was localized as a tumoral bridge between two ovaries, we performed maximal fertility sparing surgery by preserving ovaries, tubes and uterus. After surgery, 4 courses of chemotherapy with bleomycin, etoposide, and cis-platinum were done. Alfa feto-protein became negative after 3 courses of chemotherapy and she was under observation and in good health during follow up period.

  20. From embryonic stem cells to testicular germ cell cancer-- should we be concerned?

    DEFF Research Database (Denmark)

    Almstrup, Kristian; Sonne, Si Brask; Hoei-Hansen, Christina E;

    2006-01-01

    that initial hypothesis but also indicating that CIS cells have a striking phenotypic similarity to embryonic stem cells (ESC). Many cancers have been proposed to originate from tissue-specific stem cells [so-called 'cancer stem cells' (CSC)] and we argue that CIS may be a very good example of a CSC......, but with exceptional features due to the retention of embryonic pluripotency. In addition, considering the fact that pre-invasive CIS cells are transformed from early fetal cells, possibly due to environmentally induced alterations of the niche, we discuss potential risks linked to the uncontrolled therapeutic use......Since the discovery of testicular carcinoma in situ (CIS) -- the precursor cell for the vast majority of germ cell tumours -- it has been proposed that CIS cells could be derived from transformed primordial germ cells or gonocytes. Here, we review recent discoveries not only substantiating...

  1. A non-surgical approach for male germ cell mediated gene transmission through transgenesis.

    Science.gov (United States)

    Usmani, Abul; Ganguli, Nirmalya; Sarkar, Hironmoy; Dhup, Suveera; Batta, Suryaprakash R; Vimal, Manoj; Ganguli, Nilanjana; Basu, Sayon; Nagarajan, P; Majumdar, Subeer S

    2013-01-01

    Microinjection of foreign DNA in male pronucleus by in-vitro embryo manipulation is difficult but remains the method of choice for generating transgenic animals. Other procedures, including retroviral and embryonic stem cell mediated transgenesis are equally complicated and have limitations. Although our previously reported technique of testicular transgenesis circumvented several limitations, it involved many steps, including surgery and hemicastration, which carried risk of infection and impotency. We improved this technique further, into a two step non-surgical electroporation procedure, for making transgenic mice. In this approach, transgene was delivered inside both testes by injection and modified parameters of electroporation were used for in-vivo gene integration in germ cells. Using variety of constructs, germ cell integration of the gene and its transmission in progeny was confirmed by PCR, slot blot and immunohistochemical analysis. This improved technique is efficient, requires substantially less time and can be easily adopted by various biomedical researchers.

  2. Molecular biology of testicular germ cell tumors: unique features awaiting clinical application.

    Science.gov (United States)

    Boublikova, Ludmila; Buchler, Tomas; Stary, Jan; Abrahamova, Jitka; Trka, Jan

    2014-03-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men characterized by distinct biologic features and clinical behavior. Both genetic predispositions and environmental factors probably play a substantial role in their etiology. TGTCs arise from a malignant transformation of primordial germ cells in a process that starts prenatally, is often associated with a certain degree of gonadal dysgenesis, and involves the acquirement of several specific aberrations, including activation of SCF-CKIT, amplification of 12p with up-regulation of stem cell genes, and subsequent genetic and epigenetic alterations. Their embryonic and germ origin determines the unique sensitivity of TGCTs to platinum-based chemotherapy. Contrary to the vast majority of other malignancies, no molecular prognostic/predictive factors nor targeted therapy is available for patients with these tumors. This review summarizes the principal molecular characteristics of TGCTs that could represent a potential basis for development of novel diagnostic and treatment approaches. PMID:24182421

  3. Saudi Oncology Society and Saudi Urology Association combined clinical management guidelines for testicular germ cell tumors

    Directory of Open Access Journals (Sweden)

    Mohammed Alotaibi

    2016-01-01

    Full Text Available This is an update to the previously published Saudi guidelines for the evaluation, medical, and surgical management of patients diagnosed with testicular germ cell tumors. It is categorized according to the stage of the disease using the tumor-node-metastasis staging system 7th edition. The guidelines are presented with supporting evidence level, they are based on comprehensive literature review, several internationally recognized guidelines, and the collective expertise of the guidelines committee members (authors who were selected by the Saudi Oncology Society and Saudi Urological Association. Considerations to the local availability of drugs, technology and expertise have been regarded. These guidelines should serve as a roadmap for the urologists, oncologists, general physicians, support groups, and health care policy makers in the management of patients diagnosed with testicular germ cell tumors.

  4. Twisted mixed germ cell tumor of the ovary in a child

    International Nuclear Information System (INIS)

    We report an 8-year-old female patient with a mixed germ cell stromal tumor (MGCT) of the left ovary. Exploration revealed that the tumor have been twisted around its pedicle. These ovarian tumors are classified among interesting type of tumors due to the variability of neoplastic tissues in the same tumor mass, in the twisted ovarian tumor. Four histological types of tumor tissues were found: well-differentiated adenocarcinoma, dysgerminoma, immature teratoma, and focus of papillary serous cyst adenoma as well. During our review of the literature, this reported case of MGCT of the ovary was among the extremely rare cases, which had been reported. Mixed germ cell tumor is well documented in the literature since 1950. (author)

  5. Pulmonary Function in Patients With Germ Cell Cancer Treated With Bleomycin, Etoposide, and Cisplatin

    DEFF Research Database (Denmark)

    Lauritsen, Jakob; Kier, Maria Gry Gundgaard; Bandak, Mikkel;

    2016-01-01

    expiratory volume in 1 second and forced vital capacity remained unchanged after BEP but increased significantly to levels above pretreatment during follow-up. International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic group, mediastinal primary, pulmonary metastases, and smoking all......PURPOSE: For patients with germ cell cancer, various pulmonary toxicity risk factors have been hypothesized for treatment with bleomycin, etoposide, and cisplatin (BEP). Because existing studies have shortcomings, we present a large, unselected cohort of patients who have undergone close monitoring...... of lung function before, during, and after treatment with BEP to disclose valid pulmonary toxicity risk factors. PATIENTS AND METHODS: All patients who were treated with BEP at Rigshospitalet, Copenhagen, Denmark, from 1984 to 2007, were included. Pulmonary function tests (PFTs) that measured...

  6. Examination for intratubular germ cell neoplasia at operation for undescended testis in boys

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Frisch, M;

    1994-01-01

    A total of 843 consecutive boys (median age 12.7 years) who had undergone testicular biopsy at operation for undescended testis was followed into adulthood (median age 25.2 years) to examine for testicular germ cell neoplasia. Five cases of testicular germ cell neoplasia were identified, including...... testicular biopsy from the patient in whom nonseminoma was noted at followup showed Sertoli cells only. We recommend that testicular biopsy be performed at operation for undescended testis in boys with abnormal sex chromosomes, particularly 45,X/46,XY karyotype, and in those with abnormal external genitalia....... The pattern of Sertoli cells only in biopsies from boys does not preclude the occurrence of testicular cancer in adulthood....

  7. Germ cells and the origins of mammalian pluripotent cells

    NARCIS (Netherlands)

    Kuijk, E.W.

    2009-01-01

    Mammalian embryonic stem (ES) cells originate from preimplantation embryos and can be propagated indefinitely without loss of pluripotency; i.e. the potential to develop into any embryonic cell type. ES cells have been described for mouse, rhesus monkey, and human. There is considerable interest in

  8. Direct conversion of C. elegans germ cells into specific neuron types

    OpenAIRE

    Tursun, Baris; Patel, Tulsi; Kratsios, Paschalis; Hobert, Oliver

    2010-01-01

    The ability of transcription factors to directly reprogram the identity of cell types is usually restricted and is defined by cellular context. We show here that through ectopic expression of single C. elegans transcription factors, the identity of mitotic germ cells can be directly converted into that of specific neuron types (glutamatergic, cholinergic or GABAergic). This reprogramming event requires the removal of the histone chaperone LIN-53/RbAp48, a component of several histone remodeli...

  9. CT and MRI findings in patients with suprasellar germ cell tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kasamo, Shizuya; Asakura, Tetsuhiko; Nakamura, Katsumi; Nakayama, Masaki; Hirano, Hirobumi; Ohyama, Hiroshi (Kagoshima Univ. (Japan). Faculty of Medicine)

    1992-06-01

    This is a retrospective analysis of CT and MRI findings in suprasellar germ cell tumors. The study population was comprised of 6 patients with germinomas, one with embryonal carcinoma, and one with mature teratoma. Suprasellar germinoma tended to have intratumoral low density on CT or intensity area on MRI, indicating tumor necrosis or occasionally cyst formation. Germinoma tissue may extend into the pituitary fossa. Sagittal MRI revealed that the extension was limited to the posterior part of the pituitary gland. MRI of the teratoma did not demonstrate extension of the tumor into the pituitary fossa. No germ cell tumor in this region was seen as calcification. Germinoma in this region did not always show marked homogeneous enhancement. These neuroradiological findings failed to determine subtypes of germ cell tumors. Two patients had germinomas in both the pineal and suprasellar areas. Two years after the total removal of pineal teratoma, it recurred in the suprasellar region that was not seen on the first MRI. In these two patients, germinomas called 'double midline tumors' seemed to have originated by CSF dissemination or subependymal seeding, which was not demonstrated on neuroradiological images. The teratoma case was thought to be one form of double midline tumor, because the first tumor tissue in the pineal region had been totally and extracapsulary removed two years earlier and the suprasellar lesion could not be demonstrated on sagittal MRI or CT scans. In conclusion, not only neuroradiological findings but also clinical findings such as tumor markers may be required in preoperative diagnosis of suprasellar germ cell tumors. (N.K.).

  10. Ovarian Malignant Mixed Germ Cell Tumor: A Case of Unusual Presentation as Molar Pregnancy

    OpenAIRE

    Aminimoghaddam, Soheila; Mohseni, Iman; Afzalzadeh, Azadeh; Esmaeeli, Shooka

    2016-01-01

    Background: This research was conducted to introduce a patient with rare ovarian mixed germ cell tumor, presented as molar pregnancy. Case Presentation: The patient was a 16 year old woman admitted with diagnosis of molar pregnancy. Abdominal enlargement was the only complaint. She had a large pelvic mass in physical examination. The first diagnosis was molar pregnancy due to previous ultrasonic reports and positive βeta HCG. Urine pregnancy test was positive. As suction curettage was perform...

  11. A Case of Nongerminomatous Germ Cell Tumor with Fulminant Course Concomitant Leptomeningeal Metastasis.

    Science.gov (United States)

    Jeong, Youn-Beom; Wang, Kyu-Chang; Phi, Ji Hoon; Lee, Ji Yeoun; Cheon, Jung-Eun; Kang, Hyoung Jin; Kim, Il Han; Kim, Seung-Ki

    2016-04-01

    We present the case of a 9-year-old boy with a non-germinomatous germ cell tumor (NGGCT) in the pineal gland that exhibited a fulminant course following chemo- and radiotherapy. After the detection of the tiny cerebellar enhancing nodule at the end of chemo- and radiotherapy, tumor seeding progressed rapidly into the entire cisternal space. We herein report a rare case of NGGCT with fulminant clinical course of concomitant cerebellar seeding, with review of literature. PMID:27195258

  12. 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...... CIS; therefore, contralateral biopsy is recommended at the time of orchidectomy. Further research is warranted to identify causal factors explaining the increasing incidence of TGCT and to obtain a method of non-invasive CIS detection....

  13. Critical period of nonpromoter DNA methylation acquisition during prenatal male germ cell development.

    Directory of Open Access Journals (Sweden)

    Kirsten M Niles

    Full Text Available The prenatal period of germ cell development is a key time of epigenetic programming in the male, a window of development that has been shown to be influenced by maternal factors such as dietary methyl donor supply. DNA methylation occurring outside of promoter regions differs significantly between sperm and somatic tissues and has recently been linked with the regulation of gene expression during development as well as successful germline development. We examined DNA methylation at nonpromoter, intergenic sequences in purified prenatal and postnatal germ cells isolated from wildtype mice and mice deficient in the DNA methyltransferase cofactor DNMT3L. Erasure of the parental DNA methylation pattern occurred by 13.5 days post coitum (dpc with the exception of approximately 8% of loci demonstrating incomplete erasure. For most loci, DNA methylation acquisition occurred between embryonic day 13.5 to 16.5 indicating that the key phase of epigenetic pattern establishment for intergenic sequences in male germ cells occurs prior to birth. In DNMT3L-deficient germ cells at 16.5 dpc, average DNA methylation levels were low, about 30% of wildtype levels; however, by postnatal day 6, about half of the DNMT3L deficiency-specific hypomethylated loci had acquired normal methylation levels. Those loci normally methylated earliest in the prenatal period were the least affected in the DNMT3L-deficient mice, suggesting that some loci may be more susceptible than others to perturbations occurring prenatally. These results indicate that the critical period of DNA methylation programming of nonpromoter, intergenic sequences occurs in male germline progenitor cells in the prenatal period, a time when external perturbations of epigenetic patterns could result in diminished fertility.

  14. Primordial germ cells: the first cell lineage or the last cells standing?

    OpenAIRE

    Johnson, Andrew D.; Alberio, Ramiro

    2015-01-01

    Embryos of many animal models express germ line determinants that suppress transcription and mediate early germ line commitment, which occurs before the somatic cell lineages are established. However, not all animals segregate their germ line in this manner. The ‘last cell standing’ model describes primordial germ cell (PGC) development in axolotls, in which PGCs are maintained by an extracellular signalling niche, and germ line commitment occurs after gastrulation. Here, we propose that this...

  15. Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1.

    Directory of Open Access Journals (Sweden)

    Anne R Greenlee

    Full Text Available MicroRNAs (miRNAs are a class of endogenous, non-coding RNAs that mediate post-transcriptional gene silencing by inhibiting mRNA translation and promoting mRNA decay. DICER1, an RNase III endonuclease encoded by Dicer1, is required for processing short 21-22 nucleotide miRNAs from longer double-stranded RNA precursors. Here, we investigate the loss of Dicer1 in mouse postnatal male germ cells to determine how disruptions in the miRNA biogenesis pathway may contribute to infertility. Reduced levels of Dicer1 transcripts and DICER1 were confirmed in germ cell knock-out (GCKO testes by postnatal day 18 (P18. Compared to wild-type (WT at 8 weeks, GCKO males had no change in body weight; yet showed significant reductions in testis mass and sperm number. Histology and fertility tests confirmed spermatogenic failure in GCKO males. Array analyses at P18 showed that in comparison to WT testes, 75% of miRNA genes and 37% of protein coding genes were differentially expressed in GCKO testes. Among these, 96% of miRNA genes were significantly down-regulated, while 4% miRNA genes were overexpressed. Interestingly, we observed preferential overexpression of genes encoded on the sex chromosomes in GCKO testes, including more than 80% of previously identified targets of meiotic sex chromosome inactivation (MSCI. Compared to WT, GCKO mice showed higher percentages of germ cells at early meiotic stages (leptotene and zygotene but lower percentages at later stages (pachytene, diplotene and metaphase I providing evidence that deletion of Dicer1 leads to disruptions in meiotic progression. Therefore, deleting Dicer1 in early postnatal germ cells resulted in deregulation of transcripts encoded by genes on the sex chromosomes, impaired meiotic progression and led to spermatogenic failure and infertility.

  16. Inhibitory Effects of Some Philippine Medicinal Plants on Germ Cell Genotoxicity of Methylmethansulfonate, Tetracycline, and Chloromycetin

    Directory of Open Access Journals (Sweden)

    Clara Lim-Sylianco

    1990-12-01

    Full Text Available Methylmethansulfonate, tetracyline, and chloromycetin were shown to be genetoxic to germ cell. These genotoxins induced reduction in fertility index, gestation index, and implantation index. The percentage dead implants and percentage of females with resorptions were increased.Decoctions from bayabas, kalatsutsi, kamias, kogon, makabuhay, malunggay, mayana, sambong, tanglad, and ulasimang bato increased fertility index, gestation index, implantation index, and reduced percentage dead implants and percentage of female with resorption.

  17. Mixed germ cell tumor of mediastinum/lung masquerading as hemangioma in fine needle biopsy

    Directory of Open Access Journals (Sweden)

    Rathna Nuti

    2013-01-01

    Full Text Available The histological predominance of one component in a germ cell tumor can lead to a mistaken diagnosis. Here, we describe a mediastinal teratoma with predominant vascular proliferation (>90% which on fine needle biopsy was diagnosed as a pulmonary hemangioma. Later, resection specimen revealed other components constituting ~4%, changing the diagnosis while illustrating theimportance of careful evaluation. A 37-year-old Caucasian male with shortness of breath, weight loss, and history of recently resolved pneumonia was diagnosed with hemangioma, after a computed tomography guided fine needle biopsy of a -16.3-cm mediastinal pulmonary mass revealed abundant benign vascular elements. Following tumor excision, ~94% of the sample exhibited predominant vascular elementsThe mass also exhibited rare focal areas of malignant epithelium in a reticular arrangement and undifferentiated pleomorphic cells associated with vascular invasion. These atypical epithelial cells were positive for CD30, pan CK, AFP, β-HCG and CD 117, thusprocuring a diagnosis of mediastinal mixed germ cell tumor. Although mixed germ cell tumors consist of various tissue types, diagnosis can be easily overlooked if one component dominates. Therefore, obtaining adequate representative neoplasm samples, and sectioning the samples thoroughly, searching for coexisting tissue types is critical for accurate diagnosis.

  18. Effects of Nitrobenzenes on DNA Damage in Germ Cells of Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The single cell gel electrophoresis(SCGE) technique was used to detect DNA damage in germ cells of rats, which was induced by five tested nitroaromatic compounds. Mixed cultures of Sertoli and germ cells were prepared from the rats testis and their responses to m-dinitrobenzene(m-DNB), 2,4-dinitrotoluene(2,4-DNT), 2,6-dinitroto-luene(2,6-DNT), 4-nitrotoluene(4-NT) and 2,4-dinitroaniline(2,4-DNAn) were studied. The results show that all the five chemicals have a reproductive toxicity. Each dose group and the control group were significantly different(P<0.01). All of them can lead to the damage to DNA in the germ cells of Kunming male rats in the definite range of concentration(m-DNB: 0.04-25 μmol/L; 2,4-DNT, 2,6-DNT and 4-NT: 0.032-500 μmol/L; 2,4-DNAn: 0.8-20 μmol/L). When the concentration increases, the damage rate will become higher, which shows an evident logarithm dose-effect relationship.

  19. α-Fetoprotein-producing ovarian tumor in a postmenopausal woman with germ cell differentiation.

    Science.gov (United States)

    Meguro, Shiori; Yasuda, Masanori

    2013-02-01

    α-Fetoprotein (AFP)-producing ovarian tumors (APOTs) are rarely encountered in postmenopausal women, irrespective of whether they are of the germ cell or non-germ cell type. The APOTs that do occur in postmenopausal women are characterized by variable histologies such as hepatoid carcinoma, yolk sac tumor, and epithelial malignancies, most of which are combined. We herein present a case with APOT, which arose in a 58-year-old, gravida 2, para 2, postmenopausal woman. Preoperatively, the tumor, which was in the right ovary, was found to produce AFP (102768.0 ng/mL). The tumor was evenly composed of glands mimicking secretory endometrial gland or fetal gut accompanied by abundant stroma. Immunohistochemically, these glands were positive for SALL4, glypican-3, and hepatocyte nuclear factor 1β. We considered the present case as an AFP-producing adenocarcinoma with adenofibroma showing germ cell differentiation, but it seemed controversial that this tumor should be designated as a yolk sac tumor of the glandular type. The expression profiles of SALL4, OCT4, glypican-3, and hepatocyte nuclear factor 1β were thought to provide interesting implications to characterize the present case. PMID:22056036

  20. High-resolution telomere fluorescence in situ hybridization reveals intriguing anomalies in germ cell tumors.

    Science.gov (United States)

    Shekhani, Mohammed Talha; Barber, John R; Bezerra, Stephania M; Heaphy, Christopher M; Gonzalez Roibon, Nilda Diana; Taheri, Diana; Reis, Leonardo O; Guner, Gunes; Joshu, Corinne E; Netto, George J; Meeker, Alan K

    2016-08-01

    Testicular germ cell tumor (TGCT) is the most common malignancy of young men. Most patients are completely cured, which distinguishes these from most other malignancies. Orchiectomy specimens (n=76) were evaluated using high-resolution (single-cell discriminative) telomere-specific fluorescence in situ hybridization (FISH) with simultaneous Oct4 immunofluorescence to describe telomere length phenotype in TGCT neoplastic cells. For the first time, the TGCT precursor lesion, germ cell neoplasia in situ (GCNIS) is also evaluated in depth. The intensity of the signals from cancerous cells was compared to the same patient's reference cells-namely, healthy germ cells (defined as "medium" length) and interstitial/somatic cells (defined as "short" telomere length). We observed short telomeres in most GCNIS and pure seminomas (P=.006 and P=.0005, respectively). In contrast, nonseminomas displayed longer telomeres. Lesion-specific telomere lengths were documented in mixed tumor cases. Embryonal carcinoma (EC) demonstrated the longest telomeres. A fraction of EC displays the telomerase-independent alternative lengthening of telomeres (ALT) phenotype (24% of cases). Loss of ATRX or DAXX nuclear expression was strongly associated with ALT; however, nuclear expression of both proteins was retained in half of ALT-positive ECs. The particular distribution of telomere lengths among TGCT and GCNIS precursors implicate telomeres anomalies in pathogenesis. These results may advise management decisions as well. PMID:27085557

  1. Complete in vitro generation of fertile oocytes from mouse primordial germ cells.

    Science.gov (United States)

    Morohaku, Kanako; Tanimoto, Ren; Sasaki, Keisuke; Kawahara-Miki, Ryouka; Kono, Tomohiro; Hayashi, Katsuhiko; Hirao, Yuji; Obata, Yayoi

    2016-08-01

    Reconstituting gametogenesis in vitro is a key goal for reproductive biology and regenerative medicine. Successful in vitro reconstitution of primordial germ cells and spermatogenesis has recently had a significant effect in the field. However, recapitulation of oogenesis in vitro remains unachieved. Here we demonstrate the first reconstitution, to our knowledge, of the entire process of mammalian oogenesis in vitro from primordial germ cells, using an estrogen-receptor antagonist that promotes normal follicle formation, which in turn is crucial for supporting oocyte growth. The fundamental events in oogenesis (i.e., meiosis, oocyte growth, and genomic imprinting) were reproduced in the culture system. The most rigorous evidence of the recapitulation of oogenesis was the birth of fertile offspring, with a maximum of seven pups obtained from a cultured gonad. Moreover, cryopreserved gonads yielded functional oocytes and offspring in this culture system. Thus, our in vitro system will enable both innovative approaches for a deeper understanding of oogenesis and a new avenue to create and preserve female germ cells. PMID:27457928

  2. Unilateral multifocal testicular biopsies in 320 patients with germ cell aplasia

    Directory of Open Access Journals (Sweden)

    D Jamali Zavareii. M

    2007-05-01

    Full Text Available Background: Germ cell aplasia (G.C.A is one of the most important testicular causes of infertility and azospermia.In this condition the seminiferous tubules are only lined by a single layer of sertoli cell. In some cases, there is focal area with spermatogenic activity. Methods: We studied infertile men with G.C.A referred to Jahade Daneshgahi of Iran during 1381-82, retrospectively. All the cases had more than one biopsy of one testis. Results: In 11.6٪ of 320 cases, comparison of multiple biopsy sites of a testis revealed: when one site showed G.C.A, another site revealed areas with spermatogenic activity. Considering the cases who showed germ cells in both sites, 15.3٪ of cases multiple biopsy sites appeared to have focal spermatogenesis, better maturation of germ cells or higher scoring area for urologic operation. Conclusion: According to new techniques in treatment of infertility with ICSI (intra cytoplasmic sperm injection in which fertility is possible with one spermatozoa or even spermatid (after recovery, biopsy of multiple sites instead of only one site is highly recommended in azospermic patient.

  3. Membrane-bound steel factor maintains a high local concentration for mouse primordial germ cell motility, and defines the region of their migration.

    Directory of Open Access Journals (Sweden)

    Ying Gu

    Full Text Available Steel factor, the protein product of the Steel locus in the mouse, is a multifunctional signal for the primordial germ cell population. We have shown previously that its expression accompanies the germ cells during migration to the gonads, forming a "travelling niche" that controls their survival, motility, and proliferation. Here we show that these functions are distributed between the alternatively spliced membrane-bound and soluble forms of Steel factor. The germ cells normally migrate as individuals from E7.5 to E11.5, when they aggregate together in the embryonic gonads. Movie analysis of Steel-dickie mutant embryos, which make only the soluble form, at E7.5, showed that the germ cells fail to migrate normally, and undergo "premature aggregation" in the base of the allantois. Survival and directionality of movement is not affected. Addition of excess soluble Steel factor to Steel-dickie embryos rescued germ cell motility, and addition of Steel factor to germ cells in vitro showed that a fourfold higher dose was required to increase motility, compared to survival. These data show that soluble Steel factor is sufficient for germ cell survival, and suggest that the membrane-bound form provides a higher local concentration of Steel factor that controls the balance between germ cell motility and aggregation. This hypothesis was tested by addition of excess soluble Steel factor to slice cultures of E11.5 embryos, when migration usually ceases, and the germ cells aggregate. This reversed the aggregation process, and caused increased motility of the germ cells. We conclude that the two forms of Steel factor control different aspects of germ cell behavior, and that membrane-bound Steel factor controls germ cell motility within a "motility niche" that moves through the embryo with the germ cells. Escape from this niche causes cessation of motility and death by apoptosis of the ectopic germ cells.

  4. An unusual mixed germ cell tumor of the testis consisting of rhabdomyosarcoma, mature teratoma and yolk sac tumor

    Institute of Scientific and Technical Information of China (English)

    Eva Lovri(c); Dubravka Bobonj Hi(z)ak; Melita Peri(c) Balja; Tanja Leni(c)ek; Bo(z)o Kru(s)lin

    2010-01-01

    @@ Dear Editor, We recently encountered a rare case of testicular mixed germ cell tumor (MGCT) in a 32-year-old man. The tumor was composed of a combination of a yolk sac tumor, teratoma and rhabdomyosarcomatous somatic type malignancy.

  5. Immature Teratoma with Embryonal Carcinoma; a Rare Malignant Mixed Germ Cell Tumor in a 13-Year-Old Girl

    OpenAIRE

    Rana, Shweta; Gill, Manmeet¬_Kaur; Kalhan, Shivani¬; Satarkar, Rahul N; Sangwaiya, Ashok; Singh, Pawan

    2016-01-01

    Malignant mixed germ cell tumors,though rare overall, are the most common type of malignant ovarian neoplasms in young and adolescent girls. These tumors are rapidly growing and can metastasize. We report a case of 13-yr-old girl who presented at SHKM GMC, Nalhar, Mewat, Haryana, India in December 2013 with huge abdominal lump of a malignant mixed germ cell tumor comprising both immature teratoma and embryonal carcinoma. This report illustrates the aggressiveness of this tumor and emphasises ...

  6. Increased risk of carcinoma in situ in patients with testicular germ cell cancer with ultrasonic microlithiasis in the contralateral testicle

    DEFF Research Database (Denmark)

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

    2003-01-01

    We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia.......We compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia....

  7. Interaction of Insulin-like Growth Factor-binding Protein-3 and BAX in Mitochondria Promotes Male Germ Cell Apoptosis

    OpenAIRE

    Jia, Yue; Lee, Kuk-Wha; Swerdloff, Ronald; Hwang, David; Cobb, Laura J.; Sinha Hikim, Amiya; Lue, Yan He; Cohen, Pinchas; Wang, Christina

    2009-01-01

    Germ cell apoptosis is crucial for spermatogenesis and can be triggered by various stimuli, including intratesticular hormone deprivation. This study proposes a role for insulin-like growth factor binding protein-3 (IGFBP-3) in male germ cell apoptosis. Groups of adult Sprague-Dawley male rats received one of the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of the gonadotropin-releasing hormone antagonis...

  8. Salvage therapy in patients with germ cell tumors.

    Science.gov (United States)

    Einhorn, Lawrence H

    2015-01-01

    Testicular cancer is the most curable metastatic solid tumor. Initial chemotherapy is evidence based with risk stratification into three prognostic categories: good, intermediate, and advanced disease. Guidelines for disease management following progression after initial cisplatin combination chemotherapy are less clear. Options include salvage surgery for patients with anatomically confined relapse, standard-dose cisplatin combination chemotherapy, or high-dose chemotherapy with carboplatin plus etoposide with peripheral blood stem cell transplantation. Proper interpretation of a presumed relapse can be complicated. Growing masses on imaging studies might reflect a growing teratoma. Persistent elevations of serum human chorionic gonadotropin (hCG) or alpha fetoprotein (AFP) are only an indication for salvage therapy if there is a definitive rise in the tumor marker. Elevated and rising serum hCG as the only evidence of recurrence can be because of cross reactivity with luteinizing hormone or usage of marijuana rather than progressive cancer. Elevated liver function tests can cause rising serum AFP. PMID:25993183

  9. Ovarian germ cell tumors with rhabdomyosarcomatous components and later development of growing teratoma syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Al-Jumaily Usama

    2012-01-01

    Full Text Available Abstract Introduction Development of a sarcomatous component in a germ cell tumor is an uncommon phenomenon. Most cases reported have a grim prognosis. Growing teratoma syndrome is also an uncommon phenomenon and occurs in approximately 2% to 7% of non seminomatous germ cell tumors and should be treated surgically. Case presentation We report the case of a 12-year-old Asian girl with an ovarian mixed germ cell tumor containing a rhabdomyosarcomatous component. She was treated with a germ cell tumor chemotherapy regimen and rhabdomyosarcoma-specific chemotherapy. Towards the end of her treatment, she developed a retroperitoneal mass that was increasing in size. It was completely resected, revealing a mature teratoma, consistent with growing teratoma syndrome. She is still in complete remission approximately three years after presentation. Conclusion The presence of rhabdomyosarcoma in a germ cell tumor should be treated by a combined chemotherapy regimen (for germ cell tumor and rhabdomyosarcoma. In addition, development of a mass during or after therapy with normal serum markers should raise the possibility of growing teratoma syndrome that should be treated surgically.

  10. Continuous spermatogenesis and the germ cell development strategy within the testis of the Jamaican Gray Anole, Anolis lineatopus.

    Science.gov (United States)

    Gribbins, K M; Rheubert, J L; Poldemann, E H; Collier, M H; Wilson, B; Wolf, K

    2009-09-01

    Testicular tissues from Anolis lineatopus were examined histologically to determine testicular structure, germ cell morphologies, and the germ cell development strategy employed during spermatogenesis. Anoles (N=36) were collected from southern Jamaica from October 2004 to September 2005. Testes were extracted and fixed in Trump's fixative, dehydrated, embedded in Spurr's plastic, sectioned, and stained with basic fuchsin/toluidine blue. The testes of Jamaican Anoles were composed of seminiferous tubules lined with seminiferous epithelia, similar to birds and mammals, and were spermatogenically active during every month of the year. However, spermatogenic activity fluctuated based on morphometric data for February, May and June, and September-December. Sequential increases for these months and decreases in between months in tubular diameters and epithelial heights were due to fluctuations in number of elongating spermatids and spermiation events. Cellular associations were not observed during spermatogenesis in A. lineatopus, and three or more spermatids coincided with mitotic and meiotic cells within the seminiferous epithelium. Although the germ cell generations were layered within the seminiferous epithelium, similar to birds and mammals, the actual temporal development of germ cells and bursts of sperm release more closely resembled that reported recently for other reptilian taxa. All of these reptiles were temperate species that showed considerable seasonality in terms of testis morphology and spermatogenesis. The Jamaican Gray Anole has continuous spermatogenesis yet maintains this temporal germ cell development pattern. Thus, a lack of seasonal spermatogenesis in this anole seems to have no influence on the germ cell development strategy employed during sperm development.

  11. GermlncRNA: a unique catalogue of long non-coding RNAs and associated regulations in male germ cell development.

    Science.gov (United States)

    Luk, Alfred Chun-Shui; Gao, Huayan; Xiao, Sizhe; Liao, Jinyue; Wang, Daxi; Tu, Jiajie; Rennert, Owen M; Chan, Wai-Yee; Lee, Tin-Lap

    2015-01-01

    Spermatogenic failure is a major cause of male infertility, which affects millions of couples worldwide. Recent discovery of long non-coding RNAs (lncRNAs) as critical regulators in normal and disease development provides new clues for delineating the molecular regulation in male germ cell development. However, few functional lncRNAs have been characterized to date. A major limitation in studying lncRNA in male germ cell development is the absence of germ cell-specific lncRNA annotation. Current lncRNA annotations are assembled by transcriptome data from heterogeneous tissue sources; specific germ cell transcript information of various developmental stages is therefore under-represented, which may lead to biased prediction or fail to identity important germ cell-specific lncRNAs. GermlncRNA provides the first comprehensive web-based and open-access lncRNA catalogue for three key male germ cell stages, including type A spermatogonia, pachytene spermatocytes and round spermatids. This information has been developed by integrating male germ transcriptome resources derived from RNA-Seq, tiling microarray and GermSAGE. Characterizations on lncRNA-associated regulatory features, potential coding gene and microRNA targets are also provided. Search results from GermlncRNA can be exported to Galaxy for downstream analysis or downloaded locally. Taken together, GermlncRNA offers a new avenue to better understand the role of lncRNAs and associated targets during spermatogenesis. Database URL: http://germlncrna.cbiit.cuhk.edu.hk/ PMID:25982314

  12. The ligand binding domain of GCNF is not required for repression of pluripotency genes in mouse fetal ovarian germ cells.

    Directory of Open Access Journals (Sweden)

    Leah M Okumura

    Full Text Available In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes Oct4 and Nanog. Interestingly, these genes are repressed at different developmental timepoints in germ and somatic cells. Ovarian germ cells maintain their expression until about embryonic day (E 14.5, whereas somatic cells silence them much earlier, at about E8.0. In both somatic cells and embryonic stem cells, silencing of Oct4 and Nanog requires the nuclear receptor GCNF. However, expression of the Gcnf gene has not been investigated in fetal ovarian germ cells, and whether it is required for silencing Oct4 and Nanog in that context is not known. Here we demonstrate that Gcnf is expressed in fetal ovarian germ cells, peaking at E14.5, when Oct4 and Nanog are silenced. However, conditional ablation of the ligand-binding domain of Gcnf using a ubiquitous, tamoxifen-inducible Cre indicates that Gcnf is not required for the down-regulation of pluripotency genes in fetal ovarian germ cells, nor is it required for initiation of meiosis and oogenesis. These results suggest that the silencing of Oct4 and Nanog in germ cells occurs via a different mechanism from that operating in somatic cells during gastrulation.

  13. The Nanos3-3'UTR is required for germ cell specific NANOS3 expression in mouse embryos.

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    Hitomi Suzuki

    Full Text Available BACKGROUND: The regulation of gene expression via a 3' untranslated region (UTR plays essential roles in the discrimination of the germ cell lineage from somatic cells during embryogenesis. This is fundamental to the continuation of a species. Mouse NANOS3 is an essential protein required for the germ cell maintenance and is specifically expressed in these cells. However, the regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we show that differences in the stability of Nanos3 mRNA between germ cells and somatic cells is brought about in a 3'UTR-dependent manner in mouse embryos. Although Nanos3 is transcribed in both cell lineages, it is efficiently translated only in the germ lineage. We also find that the translational suppression of NANOS3 in somatic cells is caused by a 3'UTR-mediated mRNA destabilizing mechanism. Surprisingly, even when under the control of the CAG promoter which induces strong ubiquitous transcription in both germ cells and somatic cells, the addition of the Nanos3-3'UTR sequence to the coding region of exogenous gene was effective in restricting protein expression in germ cells. CONCLUSIONS/SIGNIFICANCE: Our current study thus suggests that Nanos3-3'UTR has an essential role in translational control in the mouse embryo.

  14. Spag16, an axonemal central apparatus gene, encodes a male germ cell nuclear speckle protein that regulates SPAG16 mRNA expression.

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    David R Nagarkatti-Gude

    Full Text Available Spag16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the "9+2" axoneme. In Chlamydomonas, the PF20 gene encodes a single protein present in the central pair of the axoneme. Loss of PF20 prevents central pair assembly/integrity and results in flagellar paralysis. Here we demonstrate that the murine Spag16 gene encodes two proteins: 71 kDa SPAG16L, which is found in all murine cells with motile cilia or flagella, and 35 kDa SPAG16S, representing the C terminus of SPAG16L, which is expressed only in male germ cells, and is predominantly found in specific regions within the nucleus that also contain SC35, a known marker of nuclear speckles enriched in pre-mRNA splicing factors. SPAG16S expression precedes expression of SPAG16L. Mice homozygous for a knockout of SPAG16L alone are infertile, but show no abnormalities in spermatogenesis. Mice chimeric for a mutation deleting the transcripts for both SPAG16L and SPAG16S have a profound defect in spermatogenesis. We show here that transduction of SPAG16S into cultured dispersed mouse male germ cells and BEAS-2B human bronchial epithelial cells increases SPAG16L expression, but has no effect on the expression of several other axoneme components. We also demonstrate that the Spag16L promoter shows increased activity in the presence of SPAG16S. The distinct nuclear localization of SPAG16S and its ability to modulate Spag16L mRNA expression suggest that SPAG16S plays an important role in the gene expression machinery of male germ cells. This is a unique example of a highly conserved axonemal protein gene that encodes two protein products with different functions.

  15. Sexual morbidity following radiotherapy for germ cell of the testis

    Energy Technology Data Exchange (ETDEWEB)

    Tinkler, S.D.; Howard, G.C.W.; Kerr, G.R. (Western General Hospital, Edinburgh (United Kingdom))

    1992-11-01

    An anonymous questionnaire study was designed to assess sexual function after orchidectomy and radiotherapy for testicular cancer. Questionnaires were sent to: (1) 237 patients treated with orchidectomy and abdominal radio-therapy in Edinburgh from 1974 to 1988; (2) 32 patients under 'surveillance' following orchidectomy alone; (3) 402 'normal' age-matched controls. All were asked questions concerning sexual function over the preceding 6 months. All the patients were also asked the same questions with reference to the first 6 months after completion of treatment. Completed questionnaires were returned from 137 (62%) radiotherapy patients, 18 (56%) surveillance patients and 121 (35%) controls. There was a significant difference between the radiotherapy patients and the controls in almost all the parameters looked at including erection, ejaculation and libido with the treated group performing less well. In addition, almost 24% of radiotherapy patients felt disabled or disfigured by the treatment, most commonly because of the presence of only one testicle. A deterioration in sexual function was observed with increasing age. In the radiotherapy group there was no difference in response between the 2 time periods or in any of the treatment variables. The clinical significance of these observations are unclear but together with increasing information on other toxicities emerging following this therapy the role of radiation for early stage seminoma is being brought into question. This study also confirms the morbidity of orchidectomy. It is suggested that testicular implants should be offered more widely. (author). 28 refs., 6 figs.

  16. Intracranial germ cell tumors in adults. A retrospective study of 19 cases; Les tumeurs germinales cerebrales de l`adulte. Etude retrospective de 19 cas

    Energy Technology Data Exchange (ETDEWEB)

    Agranat, P.; Jedynak, P.; Epardeau, B.; Mignot, L. [Hopital Foch, 92 - Suresnes (France); Extra, J.M. [Hopital Saint-Louis, 75 - Paris (France)

    1995-12-31

    The authors report on the retrospective analysis of 19 patients with primary cerebral germ cell tumors which were treated between 1965 and 1993. Median age is 18 years (extremes: 16-55 years). There were 16 men and three women. The location of the primary tumor was the pineal area in six patients, suprasellar and hypothalamic area in five patients and other areas in eight patients. The histological pattern was non seminoma in six patients, dysgerminoma in eight; however no histological sample was obtained in five patients who did not have any particular characteristics (either cytological abnormalities or elevated tumor marker level). Three patients were treated by surgery only, eight patients received exclusive radiotherapy and eight patients had first line chemotherapy and further cranial irradiation. One was lost to follow up. Six of eight assessable patients with dysgerminoma are alive with non evolutive disease (NED) after 15 to 176 month of follow-up. One out of five assessable patients with non seminomatous tumor in NED (163 month of follow-up). Finally all five patients who have no histological subtyping are alive with NED at 24 to 138 months. The standard treatment of dysgerminoma is currently first line chemotherapy followed by relatively low-dose and limited irradiation; the standard treatment of non-seminomatous cerebral germ cell tumor is chemotherapy, the study of which is warranted with the aim to decrease the toxicity and to increase the efficacy. (authors). 36 refs., 7 tabs.

  17. Treatment-related Cardiovascular Late-effects and Exercise Training Countermeasures in Testicular Germ Cell Cancer Survivorship

    Science.gov (United States)

    Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna; Jones, Lee W.; Højman, Pernille

    2016-01-01

    Background Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. Results Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders the ‘multiple-hit hypothesis’). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. Conclusion Since exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise-oncology research in this setting, in order to provide exercise-recommendations for optimal germ cell cancer survivorship. PMID:25751759

  18. Protective Effects of Thymoquinone against Methotrexate-Induced Germ Cell Apoptosis in Male Mice

    Directory of Open Access Journals (Sweden)

    Fatemeh Sheikhbahaei

    2016-12-01

    Full Text Available Background: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of thymoquinone (TQ as a fraction of Nigella sativa on methotrexate (MTX- induced germ cell apoptosis in male mice. Materials and Methods: In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6. A single dose of MTX (20 mg/kg and different concentrations of TQ were administrated for 4 consecutive days. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL assay was performed on paraffin embedded tissue sections to analysis the occurrence of apoptosis in the testis. Reverse transcription polymerase chain reaction (RT-PCR of apoptosis-related genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. Results: In the MTX group, there was a significant increase in morphologic sign of germ cell degeneration of tubules (48 ± 0.6%, apoptotic index (AI; 2.3 ± 0.6%, as well as mRNA expression of p53 (P=0.008, caspase 8 (P=0.002, caspase 3 (P=0.005, caspase 9 (P=0.000, bax (P=0.004 and the ratio of bax/bcl-2 (P=0.000, whereas there was an decrease in the expression of bcl-2 (P=0.003, as compared to control group. In MTX+TQ groups, the data showed that different concentrations of TQ could improve the harmful effects caused by the MTX. The best protective effects were achieved in MTX+TQ (10 mg/kg. Conclusion: TQ protects testicular germ cell against MTX-induced apoptosis by affecting related genes regulation.

  19. Surrogate production of eggs and sperm by intrapapillary transplantation of germ cells in cytoablated adult fish.

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    Sullip Kumar Majhi

    Full Text Available Germ cell transplantation (GCT is a promising assisted reproductive technology for the conservation and propagation of endangered and valuable genetic resources. In teleost fish, GCT in adult gonads has been achieved only in male recipients, limiting greatly the usefulness of this technique in situations where both sexes need equal and timely attention for conservation and/or propagation. Here we describe a simplified GCT approach that ultimately leads to production of donor-derived eggs and sperm in considerably short time. Donor germ cells isolated from young pejerrey Odontesthes bonariensis (Atherinopsidae were transplanted non-surgically through the genital papilla into the sexually mature gonads of Patagonian pejerrey O. hatcheri recipients whose gonads have been depleted of endogenous GCs by heat (26°C and chemical treatment (four doses of Busulfan at 30 mg/kg and 40 mg/kg for females and males, respectively. Transplanted spermatogonial and oogonial cells were able to recolonize the recipients' gonads and produce functional donor origin eggs and sperm within 7 months from the GCT. We confirmed the presence of donor-derived gametes by PCR in 17% and 5% of the surrogate O. hatcheri fathers and mothers, respectively. The crosses between surrogate fathers and O. bonariensis mothers yielded 12.6-39.7% pure O. bonariensis and that between a surrogate mother and an O. bonariensis father yielded 52.2% pure O. bonariensis offspring. Our findings confirm that transplantation of germ cells into sexually competent adult fish by non-surgical methods allows the production of functional donor-derived eggs and sperm in a considerably short time. The methods described here could play a vital role in conservation and rapid propagation of endangered fish genetic resources.

  20. Germ cell toxicity: significance in genetic and fertility effects of radiation and chemicals

    International Nuclear Information System (INIS)

    The primordial germ cells originate in the region of the caudal end of the primitive streak, root of the allantois, and yolk sac splanchnopleure, and migrate to the gonadal ridges where they divide to form the oogonia of the female and gonocytes of the male. In the female, the transition to oocytes occurs in utero, and the female mammal is born with a finite number of oocytes that cannot be replaced. By contrast, the gonocytes of the male initiate divisions soon after birth to form the spermatogonial stem cells, which persist throughout reproductive life of the male and are capable of regenerating the seminiferous epithelium after injury. As a result of these basic differences in gametogenesis, the response of the male and female to radiation and chemicals is different. The response of both the male and female changes with development of the embryonic to the adult gonad, and with differentiation and maturation in the adult. The primordial germ cells, early oocytes, and differentiating spermatogonia of the adult male are unusually sensitive to the cytotoxic action of noxious agents, but each agent elicits a specific response owing to the intricate biochemical and physiological changes associated with development and maturation of the gametes. The relationship of germ cell killing to fertility is direct, and long-term fertility effects can be predicted from histological analysis of the gonads. The relationship to genetic effects, on the other hand, is indirect, and acts primarily by limiting the cell stages available for testing, by affecting the distribution of mitotically active stem cells among the different stages of the mitotic cycle, and thereby changing both the type and frequency of genetic effects observed

  1. Prognosis after salvage treatment for unselected male patients with germ cell tumours.

    OpenAIRE

    Gerl, A; Clemm, C.; Schmeller, N.; Hartenstein, R.; Lamerz, R.; Wilmanns, W.

    1995-01-01

    Long-term outcome of salvage treatment was reviewed in 67 unselected male patients relapsing during or after their primary cisplatin-based chemotherapy for metastatic germ cell tumours. Seven patients underwent only surgery and/or radiotherapy as curatively intended salvage treatment. Thirty-five patients (52%) had a complete or partial response to salvage treatment, 20 (57%) of whom relapsed again. With a median follow-up of 90 months (range 3-143 months) 20 patients (30%) are alive with no ...

  2. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    OpenAIRE

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her ser...

  3. Mixed germ-cell testicular tumor in a liver transplant recipient

    Directory of Open Access Journals (Sweden)

    Mehdi Salehipour

    2012-01-01

    Full Text Available The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

  4. Acute scrotum due to arterial bleeding mimicking non-seminomatous germ cell tumor

    Institute of Scientific and Technical Information of China (English)

    F.Christoph; M.Schradert; A.Amirmaki; K.Miller

    2004-01-01

    Men with testicular tumors usually present with painless increase in testis size incidentally noticed by the patient. We report a case of a young patient presenting as an emergency with acute onset of massive right-sided testicular pain without previous injury. After physical examination testicular torsion could not be excluded. Ultrasound examination of the tesds was suspicious for tesdcular tumor. Surgical exploration of the right testis by inguinal approach was performed revealing subcapsular arterial bleeding due to a small nonseminomatous germ cell tumor non-palpable on clinical examination. (Asian J Andro12004 Dec;6:379-381)

  5. Primary mixed germ cell tumor of the liver with sarcomatous components

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Germ cell tumor(GCT)of the liver is extremely rare. Here,we describe a case of hepatic mixed GCT with significant sarcomatous components and elevated serum α-fetoprotein(AFP)in a 34-year-old man.Histopathologically,the tumor was composed of two GCTs components:yolk sac tumor and immature teratoma.The predominant components of immature teratoma consisted of several types of tissue that represented different germinal layers(endoderm,mesoderm and ectoderm) and showed varying degrees of differentiation with sig...

  6. Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship

    DEFF Research Database (Denmark)

    Christensen, Jesper F; Bandak, Mikkel; Campbell, Anna;

    2015-01-01

    , are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment......BACKGROUND: Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy...

  7. Germ cell specific overactivation of WNT/βcatenin signalling has no effect on folliculogenesis but causes fertility defects due to abnormal foetal development

    Science.gov (United States)

    Kumar, Manish; Camlin, Nicole J.; Holt, Janet E.; Teixeira, Jose M.; McLaughlin, Eileen A.; Tanwar, Pradeep S.

    2016-01-01

    All the major components of the WNT signalling pathway are expressed in female germ cells and embryos. However, their functional relevance in oocyte biology is currently unclear. We examined ovaries collected from TCFGFP mice, a well-known Wnt reporter mouse model, and found dynamic changes in the Wnt/βcatenin signalling activity during different stages of oocyte development and maturation. To understand the functional importance of Wnt signalling in oocytes, we developed a mouse model with the germ cell-specific constitutive activation of βcatenin using cre recombinase driven by the DEAD (Asp-Glu-Ala-Asp) box protein 4 (Ddx4) gene promoter. Histopathological and functional analysis of ovaries from these mutant mice (Ctnnb1ex3cko) showed no defects in ovarian functions, oocytes, ovulation and early embryonic development. However, breeding of the Ctnnb1ex3cko female mice with males of known fertility never resulted in birth of mutant pups. Examination of uteri from time pregnant mutant females revealed defects in ectoderm differentiation leading to abnormal foetal development and premature death. Collectively, our work has established the role of active WNT/βcatenin signalling in oocyte biology and foetal development, and provides novel insights into the possible mechanisms of complications in human pregnancy such as repeated spontaneous abortion, sudden intrauterine unexpected foetal death syndrome and stillbirth. PMID:27265527

  8. Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption.

    Science.gov (United States)

    Bösl, M R; Stein, V; Hübner, C; Zdebik, A A; Jordt, S E; Mukhopadhyay, A K; Davidoff, M S; Holstein, A F; Jentsch, T J

    2001-03-15

    The functions of some CLC Cl(-) channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC-2 Cl(-) channel is less clear. Several important functions have been attributed to ClC-2, but contrary to these expectations ClC-2-deficient mice lacked overt abnormalities except for a severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina and germ cells failed to complete meiosis. Beginning around puberty there was a massive death of primary spermatocytes and later also of spermatogonia. Tubules were filled with abnormal Sertoli cells, which normally express ClC-2 in patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, ClC-2 disruption entails the death of two cell types which depend on supporting cells that form the blood-testes and blood-retina barriers. We propose that ClC-2 is crucial for controlling the ionic environment of these cells. PMID:11250895

  9. Residual tumor after the salvage surgery is the major risk factors for primary treatment failure in malignant ovarian germ cell tumors: A retrospective study of single institution

    OpenAIRE

    Park Jong Sup; Ryu Ki Sung; Lee Keun Ho; Lee Sung Jong; Ki Eun Young; Park Sung Taek; Song Min Jong; Lee Chung Won; Hur Soo Young

    2011-01-01

    Abstract Background Malignant ovarian germ cell tumors are rare, and knowledge of their prognostic factors is limited, with little available randomized data. This study was conducted to evaluate the clinicopathologic characteristics of malignant ovarian germ cell tumors and to determine the association of their prognostic factors to primary treatment failure. Methods The medical records of 57 patients with stages I to IV malignant ovarian germ cell tumor were retrospectively reviewed, and the...

  10. Assessment of human exposures

    Energy Technology Data Exchange (ETDEWEB)

    Lebret, E. [RIVM-National Inst. of Public Health and Environmental Protection (Netherlands)

    1995-12-31

    This article describes some of the features of the assessment of human exposure to environmental pollutants in epidemiological studies. Since exposure assessment in air pollution epidemiology studies typically involve professionals from various backgrounds, interpretation of a concepts like `exposure` may vary. A brief descriptions is therefore given by way of introduction

  11. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-09-01

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.

  12. The role of MAPK and FAS death receptor pathways in testicular germ cell apoptosis induced by lead

    Institute of Scientific and Technical Information of China (English)

    Shuying Dong; Duoping Liang; Na An; Li Jia; Yujuan Shan; Chao Chen; Kuo Sun; Fei Niu; Huiyan Li; Songbin Fu

    2009-01-01

    The aim of the present study is to investigate gene expression involved in the signal pathway of MAPK and death signal receptor pathway of FAS in lead-induced apoptosis of testicular germ cells. First, cell viabilities were determined by MTT assay. Second, using single cell gel-electrophoresis test (comet assay) and TUNEL staining technique, apoptotie rate and cell apoptosis localization of testicular germ cells were measured in mice treated with 0.15%, 0.3%, and 0.6% lead, respectively. Third, the immunolocalization of K-ras, c-fos, Fas, and active caspase-3 proteins was determined by immunohistochemistry. Finally, changes in the translational levels of K-ras, c-fos, Fas, and active caspase-3 were further detected by western blot analysis. Our results showed that lead could significantly induce testicular germ cell apoptosis in a dose-dependent manner (P < 0.01). The mechanisms were closely related to the increased expressions of K-ras, c-fos, Fas, and active caspase-3 in apoptotic germ cells. In conclusion, K-ras/c-fos and Fas/caspase-3 death signaling receptor pathways were involved in the lead-induced apoptosis of the testicular germ cells in mice.

  13. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment.

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-09-09

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.

  14. 颅内生殖细胞肿瘤影像诊断%Imaging diagnosis of intracranial germ cell tumors

    Institute of Scientific and Technical Information of China (English)

    周国民; 李艳华

    2013-01-01

    Intracranial germ cell tumors (GCTs) is a rare intracranial embryonal tumors in children and adolescents, germ cell tumors from different parts of the CT, MRI performance is different, this article through to the pineal gland, saddle area and Basal ganglia area germ cell tumor of the imaging manifestations and differential diagnosis, improve the imaging diagnostic level of intracranial germ cell tumors,For intracranial germ cell tumor play a role in the early diagnosis and effective treatment.%颅内生殖细胞肿瘤(GCTs)是一种少见的颅内胚胎性肿瘤,好发于儿童及青少年,不同部位的生殖细胞肿瘤CT、MRI表现有所不同,本文通过对松果体区,鞍区及基底节区的生殖细胞肿瘤的影像表现及鉴别诊断的论述,提高了颅内生殖细胞肿瘤的影像诊断水平,为颅内生殖细胞肿瘤提供早期的诊断及有效治疗起到一定作用。

  15. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-01-01

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs. PMID:27608931

  16. Ectopic expression of Cvh (Chicken Vasa homologue) mediates the reprogramming of chicken embryonic stem cells to a germ cell fate.

    Science.gov (United States)

    Lavial, Fabrice; Acloque, Hervé; Bachelard, Elodie; Nieto, M Angela; Samarut, Jacques; Pain, Bertrand

    2009-06-01

    When they are derived from blastodermal cells of the pre-primitive streak in vitro, the pluripotency of Chicken Embryonic Stem Cells (cESC) can be controlled by the cPouV and Nanog genes. These cESC can differentiate into derivatives of the three germ layers both in vitro and in vivo, but they only weakly colonize the gonads of host embryos. By contrast, non-cultured blastodermal cells and long-term cultured chicken primordial germ cells maintain full germline competence. This restriction in the germline potential of the cESC may result from either early germline determination in the donor embryos or it may occur as a result of in vitro culture. We are interested in understanding the genetic determinants of germline programming. The RNA binding protein Cvh (Chicken Vasa Homologue) is considered as one such determinant, although its role in germ cell physiology is still unclear. Here we show that the exogenous expression of Cvh, combined with appropriate culture conditions, induces cESC reprogramming towards a germ cell fate. Indeed, these cells express the Dazl, Tudor and Sycp3 germline markers, and they display improved germline colonization and adopt a germ cell fate when injected into recipient embryos. Thus, our results demonstrate that Vasa can drive ES cell differentiation towards the germ cell lineage, both in vitro and in vivo.

  17. Design, synthesis and biological evaluation of Arylpiperazine-based novel Phthalimides: Active inducers of testicular germ cell apoptosis

    Indian Academy of Sciences (India)

    ANIL K SINGH; JITENDER K BHARDWAJ; ANA OLIVAL; YOGESH KUMAR; AVIJIT PODDER; ANKUR MAHESHWARI; RENUKA AGRAWAL; N LATHA; BRAJENDRA K SINGH; HELENA TOMÁS; JOÃO RODRIGUES; RAM KISHAN; B RUPINI; BRIJESH RATHI

    2016-08-01

    Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines aspotential apoptotic inducers. The listed twenty phthalimides were assessed for their in vitro apoptotic activity against testicular germ cells. All phthalimides showed a significant apoptotic response (∼39 to ∼68%). TUNEL assay and acridine orange fluorescence staining were carried out to investigate the molecular mechanismsresponsible for the cell death. Phthalimides exhibited substantial apoptotic induction following the intrinsic pathway mechanism. Studies advocated that the apoptotic induction was mediated through caspase-9, caspase-3, JNK MAP kinase and tumor suppressor p53, which was accompanied by DNA fragmentation and nuclearcondensation. Besides, the best five phthalimides regarding apoptotic action were evaluated for in vitro cytotoxic effects against CAL-72 and MCF-7 cancer cell lines. Compounds showed efficient killing of cancer cells. This discovery of functionalized phthalimides as apoptotic inducers would be highly valuable in understanding the mechanism of apoptosis at the molecular level and opens up new possibilities for therapeutic strategies.

  18. Genetic effects of combined chemical-X-ray treatments in male mouse germ cells

    International Nuclear Information System (INIS)

    Several studies have shown that the yield of genetic damage induced by radiation in male mouse germ cells can be modified by chemical treatments. Pre-treatments with radio-protecting agents have given contradictory results but this appears to be largely attributable to the different germ cell stages tested and dependent upon the level of radiation damage induced. Pre-treatments which enhance the yield of genetic damage have been reported although, as yet, no tests have been conducted with radio-sensitizers. Another form of interaction between chemicals and radiation is specifically found with spermatogonial stem cells. Chemicals that kill cells can, by population depletion, substantially and predictably modify the genetic response to subsequent radiation exposure over a period of several days, or even weeks. Enhancement and reduction in the genetic yield can be attained, dependent upon the interval between treatments, with the modification also varying with the type of genetic damage scored. Post-treatment with one chemical (TEM) has been shown to reduce the genetic response to radiation exposure. (author)

  19. Clinical and Radiologic Signs of Relapsed Ovarian Germ Cell Tumor: Tissue Is the Issue

    Directory of Open Access Journals (Sweden)

    M. Y. V. Homs

    2013-01-01

    Full Text Available Malignant ovarian germ cell tumor is a rare disease, but with current treatment strategies including surgery and platinum based chemotherapy survival is excellent. After treatment, intensive followup is indicated to encounter tumor relapse at an early stage. This case describes a 22-year-old female with a history of common variable immune deficiency (CVID who underwent a resection of a large ovarian germ cell tumor followed by 4 cycles of cisplatin and etoposide resulting in clinical complete remission. During followup, she developed a mass at the umbilicus and ascites. Initially, the cytology of the ascites was interpreted as tumor positive, suspicious of relapse of the disease, but tumor markers remained negative. However, during laparoscopy it turned out to be a mature teratoma, which can develop after chemotherapy, the so called growing teratoma syndrome. In retrospect, the ascites was false positive. This case shows that current diagnostic tools are not sufficient to distinguish between vital tumor and mature teratoma and can be misleading. Tumor biopsy and/or laparoscopic inspection are therefore indicated.

  20. Molecular Cloning and Functional Analysis of ESGP, an Embryonic Stem Cell and Germ Cell Specific Protein

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei CHEN; Zhong-Wei DU; Zhen YAO

    2005-01-01

    Several putative Oct-4 downstream genes from mouse embryonic stem (ES) cells have been identified using the suppression-subtractive hybridization method. In this study, one of the novel genes encoding an ES cell and germ cell specific protein (ESGP) was cloned by rapid amplification of cDNA ends.ESGP contains 801 bp encoding an 84 amino acid small protein and has no significant homology to any known genes. There is a signal peptide at the N-terminal of ESGP protein as predicted by SeqWeb (GCG)(SeqWeb version 2.0.2, http://gcg.biosino.org:8080/). The result of immunofluorescence assay suggested that ESGP might encode a secretory protein. The expression pattern of ESGP is consistent with the expression of Oct-4 during embryonic development. ESGP protein was detected in fertilized oocyte, from 3.5 day postcoital (dpc) blastocyst to 17.5 dpc embryo, and was only detected in testis and ovary tissues in adult. In vitro, ESGP was only expressed in pluripotent cell lines, such as embryonic stem cells, embryonic carcinoma cells and embryonic germ cells, but not in their differentiated progenies. Despite its specific expression,forced expression of ESGP is not indispensable for the effect of Oct-4 on ES cell self-renewal, and does not affect the differentiation to three germ layers.

  1. Germ cell dynamics during the annual reproductive cycle of Dendropsophus minutus (Anura: Hylidae).

    Science.gov (United States)

    Santos, Lia Raquel de Souza; Franco-Belussi, Lilian; de Oliveira, Classius

    2011-11-01

    Thirty male specimens of Dendropsophus minutus Peters, 1972, were collected from April 2004 to March 2005 in the region de Sao José do Rio Preto/SP, to conduct a histological study during the seasonal and annual cycles. Testicular activity was inferred based on the volume occupied by each type of cellular cyst present in the seminiferous tubules, as well as the quantity of germ cells in the final development stage, the spermatozoids. All data analyzed were correlated with climatic variables (temperature, rainfall and photoperiod) registered in the region where specimens were collected. A significant variation was verified in the quantity of spermatozoids as well as in the volume occupied by spermatids and spermatozoids throughout the year and between the cold/dry and hot/ humid seasons. It has also been reported that environmental conditions are important factors closely related to species reproduction and that production of germ cells and volume occupied by germ cysts is independent of anatomical aspect of the gonads. Thus, it was possible to verify that although the species reproduces throughout the year, individuals exhibit a preferential reproduction season, resulting in a reproductive (October to the end of February) and a post-reproductive period. PMID:22035307

  2. Microgravity promotes differentiation and meiotic entry of postnatal mouse male germ cells.

    Directory of Open Access Journals (Sweden)

    Manuela Pellegrini

    Full Text Available A critical step of spermatogenesis is the entry of mitotic spermatogonia into meiosis. Progresses on these topics are hampered by the lack of an in vitro culture system allowing mouse spermatogonia differentiation and entry into meiosis. Previous studies have shown that mouse pachytene spermatocytes cultured in simulated microgravity (SM undergo a spontaneous meiotic progression. Here we report that mouse mitotic spermatogonia cultured under SM with a rotary cell culture system (RCCS enter into meiosis in the absence of any added exogenous factor or contact with somatic cells. We found that isolated Kit-positive spermatogonia under the RCCS condition enter into the prophase of the first meiotic division (leptotene stage, as monitored by chromosomal organization of the synaptonemal complex 3 protein (Scp3 and up-regulation of several pro-meiotic genes. SM was found to activate the phosphatidyl inositol 3 kinase (PI3K pathway and to induce in Kit-positive spermatogonia the last round of DNA replication, typical of the preleptotene stage. A PI3K inhibitor abolished Scp3 induction and meiotic entry stimulated by RCCS conditions. A positive effect of SM on germ cell differentiation was also observed in undifferentiated (Kit-negative spermatogonia, in which RCCS conditions stimulate the expression of Kit and Stra8. In conclusion, SM is an artificial environmental condition which promotes postnatal male germ cell differentiation and might provide a tool to study the molecular mechanisms underlying the switch from mitosis to meiosis in mammals.

  3. Radiation biology of Caenorhabditis elegans. Germ cell response, aging and behavior

    International Nuclear Information System (INIS)

    The study of radiation effect in Caenorhabditis (C.) elegans has been carried out over three decades and now allow for understanding at the molecular, cellular and individual levels. This review describes the current knowledge of the biological effects of ionizing irradiation with a scope of the germ line, aging and behavior. In germ cells, ionizing radiation induces apoptosis, cell cycle arrest and DNA repair. Lots of molecules involved in these responses and functions have been identified in C. elegans, which are highly conserved throughout eukaryotes. Radiosensitivity and the effect of heavy-ion microbeam irradiation on germ cells with relationship between initiation of meiotic recombination and DNA lesions are discussed. In addition to DNA damage, ionizing radiation produces free radicals, and the free radical theory is the most popular aging theory. A first signal transduction pathway of aging has been discovered in C. elegans, and radiation-induced metabolic oxidative stress is recently noted for an inducible factor of hormetic response and genetic instability. The hormetic response in C. elegans exposed to oxidative stress is discussed with genetic pathways of aging. Moreover, C. elegans is well known as a model organism for behavior. The recent work reported the radiation effects via specific neurons on learning behavior, and radiation and hydrogen peroxide affect the locomotory rate similarly. These findings are discussed in relation to the evidence obtained with other organisms. Altogether, C. elegans may be a good 'in vivo' model system in the field of radiation biology. (author)

  4. Chicken primordial germ cell motility in response to stem cell factor sensing.

    Science.gov (United States)

    Srihawong, Thanida; Kuwana, Takashi; Siripattarapravat, Kannika; Tirawattanawanich, Chanin

    2015-01-01

    Avian primordial germ cells (PGCs) are destined to migrate a long distance from their extra embryonic region via the vascular system to the gonadal ridges where they form the germ cells. Although PGC migration is crucial for a genetic continuation to the next generation, the factors and mechanisms that control their migration remain largely unknown. In the present study the chemotactic effect of stem cell factor (SCF) was examined on chicken blood circulating PGCs (cPGC), employing 3D chemotaxis slides and time-lapsed imaging analyses as an in vitro study model. Upon in vitro exposure to an SCF gradient, 77.1% (54 out of 70) of cPGCs showed a clear response, of which 48.1% (26 out of 54) polarized with the consecutive formation of a persistent membrane protrusion and significant directional migration towards the gradient and the others showed transient membrane protrusions. In contrast, the controls and apparently SCF unresponsive cPGCs and c-kit-negative red blood cells (RBCs) showed only cytoplasmic cycling with random formations of membrane blebbing and no directional migration. Significant (p goat anti-mouse c-kit primary antibody, suggesting that the cPGCs were capable of SCF sensing and the potential involvement of SCF/c-kit in the chemotactic migration. Therefore, SCF is suggested to function as a chemoattractant in the migration of chicken cPGC. PMID:26864485

  5. A novel piggyBac transposon inducible expression system identifies a role for AKT signalling in primordial germ cell migration.

    Directory of Open Access Journals (Sweden)

    James D Glover

    Full Text Available In this work, we describe a single piggyBac transposon system containing both a tet-activator and a doxycycline-inducible expression cassette. We demonstrate that a gene product can be conditionally expressed from the integrated transposon and a second gene can be simultaneously targeted by a short hairpin RNA contained within the transposon, both in vivo and in mammalian and avian cell lines. We applied this system to stably modify chicken primordial germ cell (PGC lines in vitro and induce a reporter gene at specific developmental stages after injection of the transposon-modified germ cells into chicken embryos. We used this vector to express a constitutively-active AKT molecule during PGC migration to the forming gonad. We found that PGC migration was retarded and cells could not colonise the forming gonad. Correct levels of AKT activation are thus essential for germ cell migration during early embryonic development.

  6. Alternative germ cell death pathway in Drosophila involves HtrA2/Omi, lysosomes, and a caspase-9 counterpart.

    Science.gov (United States)

    Yacobi-Sharon, Keren; Namdar, Yuval; Arama, Eli

    2013-04-15

    In both flies and mammals, almost one-third of the newly emerging male germ cells are spontaneously eliminated before entering meiosis. Here, we show that in Drosophila, germ cell death (GCD) involves the initiator caspase Dronc independently of the apoptosome and the main executioner caspases. Electron microscopy of dying germ cells revealed mixed morphologies of apoptosis and necrosis. We further show that the lysosomes and their catabolic enzymes, but not macroautophagy, are involved in the execution of GCD. We then identified, in a screen, the Parkinson's disease-associated mitochondrial protease, HtrA2/Omi, as an important mediator of GCD, acting mainly through its catalytic activity rather than by antagonizing inhibitor of apoptosis proteins. Concomitantly, other mitochondrial-associated factors were also implicated in GCD, including Pink1 (but not Parkin), the Bcl-2-related proteins, and endonuclease G, which establish the mitochondria as central mediators of GCD. These findings uncover an alternative developmental cell death pathway in metazoans.

  7. Vulnerability of female germ cells in developing mice and monkeys to tritium, gamma rays, and polycyclic aromatic hydrocarbons

    International Nuclear Information System (INIS)

    During development female germ cells in both mouse and monkey are extremely sensitive to destruction by low-level chronic tritium exposure (via 3HOH in maternal drinking water). Practical significance of this stems from tritium's importance in nuclear energy production and as an environmental pollutant. In mice exposed from conception to 14 days of age, the LD50 level for oocytes is only 2 μCi per mililiter of body water. The present studies indicate that, for female germ cells in squirrel monkeys exposed in utero, the LD50 is even lower, about 0.5 μCi/ml. This striking sensitivity contrasts with reported radioresistance for primate oocytes, chiefly from acute x-irradiation experiments. The discrepancy is reconciled if germ cells in the fetal primate pass through a highly sensitive period of limited duration. In light of other data showing germ-cell loss following repeated semiweekly x-irradiation during late but not during mid gestation, these results indicate that exceedingly high sensitivity occurs probably about the middle of the last trimester, at which time the LD50 for monkey germ cells is, as for that of the mouse, less than 5 rads. Whereas highest radiosensitivity in primates is before birth, in mice it is after birth. To define the period of sensitivity more sharply, we measured oocyte responses to standard gamma-ray exposures in Swiss-Webster mice at various ages and found them to be maximal between days 5 and 19. Polycyclic aromatic hydrocarbons (PAH's), important as pollutants, also can destroy female germ cells effectively

  8. N-acetylcysteine protects against cadmium-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in testes

    Institute of Scientific and Technical Information of China (English)

    Yan-Li Ji; Hua Wang; Cheng Zhang; Ying Zhang; Mei Zhao; Yuan-Hua Chen; De-Xiang Xu

    2013-01-01

    Cadmium (Cd) is a reproductive toxicant that induces germ cell apoptosis in the testes.Previous studies have demonstrated that endoplasmic reticulum (ER) stress is involved in Cd-induced germ cell apoptosis.The aim of the present study was to investigate the effects of N-acetylcysteine (NAC),an antioxidant,on Cd-induced ER stress and germ cell apoptosis in the testes.Male CD-1 mice were intraperitoneally injected with CdCl2 (2.0 mg kg-1).As expected,acute Cd exposure induced germ cell apoptosis in the testes,as determined by terminal dUTP nick-end labelling (TUNEL).However,the administration of NAC alleviated Cd-induced germ cell apoptosis in the testes.Further analysis showed that NAC attenuated the Cd-induced upregulation of testicular glucose-regulated protein 78 (GRP78),an important ER molecular chaperone.Moreover,NAC inhibited the Cd-induced phosphorylation of testicular eukaryotic translation initiation factor 2α (elF2α),a downstream target of the double-stranded RNA-activated kinase-like ER kinase (PERK) pathway.In addition,NAC blocked the Cd-induced activation of testicular X binding protein (XBP)-1,indicating that NAC attenuates the Cd-induced ER stress and the unfolded protein response (UPR).Interestingly,NAC almost completely prevented the Cd-induced elevation of C/EBP homologous protein (CHOP) and phosphorylation of c-Jun N-terminal kinase (J NK),two components of the ER stress-mediated apoptotic pathway.In conclusion,NAC protects against Cd-induced germ cell apoptosis by inhibiting endoplasmic reticulum stress in the testes.

  9. Stirred suspension bioreactors as a novel method to enrich germ cells from pre-pubertal pig testis.

    Science.gov (United States)

    Dores, C; Rancourt, D; Dobrinski, I

    2015-05-01

    To study spermatogonial stem cells the heterogeneous testicular cell population first needs to be enriched for undifferentiated spermatogonia, which contain the stem cell population. When working with non-rodent models, this step requires working with large numbers of cells. Available cell separation methods rely on differential properties of testicular cell types such as expression of specific cell surface proteins, size, density, or differential adhesion to substrates to separate germ cells from somatic cells. The objective of this study was to develop an approach that allowed germ cell enrichment while providing efficiency of handling large cell numbers. Here, we report the use of stirred suspension bioreactors (SSB) to exploit the adhesion properties of Sertoli cells to enrich cells obtained from pre-pubertal porcine testes for undifferentiated spermatogonia. We also compared the bioreactor approach with an established differential plating method and the combination of both: SSB followed by differential plating. After 66 h of culture, germ cell enrichment in SSBs provided 7.3 ± 1.0-fold (n = 9), differential plating 9.8 ± 2.4-fold (n = 6) and combination of both methods resulted in 9.1 ± 0.3-fold enrichment of germ cells from the initial germ cell population (n = 3). To document functionality of cells recovered from the bioreactor, we demonstrated that cells retained their functional ability to reassemble seminiferous tubules de novo after grafting to mouse hosts and to support spermatogenesis. These results demonstrate that the SSB allows enrichment of germ cells in a controlled and scalable environment providing an efficient method when handling large cell numbers while reducing variability owing to handling.

  10. Immature Teratoma with Embryonal Carcinoma; a Rare Malignant Mixed Germ Cell Tumor in a 13-Year-Old Girl.

    Science.gov (United States)

    Rana, Shweta; Gill, Manmeet Kaur; Kalhan, Shivani; Satarkar, Rahul N; Sangwaiya, Ashok; Singh, Pawan

    2016-01-01

    Malignant mixed germ cell tumors,though rare overall, are the most common type of malignant ovarian neoplasms in young and adolescent girls. These tumors are rapidly growing and can metastasize. We report a case of 13-yr-old girl who presented at SHKM GMC, Nalhar, Mewat, Haryana, India in December 2013 with huge abdominal lump of a malignant mixed germ cell tumor comprising both immature teratoma and embryonal carcinoma. This report illustrates the aggressiveness of this tumor and emphasises the need of early diagnosis and treatment. PMID:26870146

  11. Co-culture of Mouse Embryonic Stem Cells with Sertoli Cells Promote in vitro Generation of Germ Cells

    OpenAIRE

    Mohammad Miryounesi; Karim Nayernia; Mahdi Dianatpour; Fatemeh Mansouri; Mohammad Hossein Modarressi

    2013-01-01

      Objective(s): Sertoli cells support in vivo germ cell production; but, its exact mechanism has not been well understood. The present study was designed to analyze the effect of Sertoli cells in differentiation of mouse embryonic stem cells (mESCs) to germ cells.   Materials and Methods: A fusion construct composed of a Stra8 gene promoter and the coding region of enhanced green fluorescence protein was produced to select differentiated mESCs. To analyze sertoli cells’ effect in differentiat...

  12. One to Watch: A Germ Cell Tumor Arising in an Undescended Testicle in Rubinstein-Taybi Syndrome.

    Science.gov (United States)

    Butler, Grainne H; Boyle, Michael; Lynch, Sally Ann; Ryan, Stephanie; McDermott, Michael; Capra, Michael

    2016-08-01

    A male preterm infant was born with dysmorphic features consistent with Rubinstein-Taybi syndrome (RTS). An undescended right testicle was noted on examination. At 5 months of age he developed a palpable right-sided abdominal mass and an elevated alpha-fetoprotein. Histology revealed a malignant germ cell neoplasm arising within the undescended testis. This is the first reported case of a germ cell tumor occurring in a pediatric patient with RTS. Urologic abnormalities occur in approximately 52% of RTS patients, of which cryptorchidism is the commonest. Given the frequency of undescended testes in this population, closer screening may be warranted.

  13. The potential for archiving and reconstituting valuable strains of turkey (Meleagris gallopavo) using primordial germ cells.

    Science.gov (United States)

    Wade, Alexander J; French, Nick A; Ireland, Grenham W

    2014-04-01

    Diseases such as avian influenza can destroy turkey flocks, potentially resulting in the loss of valuable or rare genetic material. Consequently, there is an urgent need to develop a means to archive such germplasm. Germline chimeras produced by intravascular transfer of primordial germ cells (PGC) have been reported in other avian species but not turkeys. This study examined the feasibility of both establishing an archive of frozen PGC, and producing germline chimeras by injecting the thawed PGC into host embryos. To meet these aims, the following experiments were performed: (1) PGC identification within turkey embryos; (2) development of an efficient method for isolation of turkey PGC; (3) demonstration that PGC can be cryopreserved, recovered, and retain viability; (4) reinjection into embryos and detection of injected PGC. Primordial germ cells were identified using periodic acid-Schiff reagent and the immunological marker OLP-1. Bloodstream PGC were isolated using Ficoll density gradient centrifugation with PGC recovery peaking at stages 13, 14, and 15 with 32 ± 4.9, 33 ± 6.4, and 26 ± 5.4 PGC recovered, respectively. Primordial germ cells were frozen using Dulbecco's modified Eagle medium, 20% fetal calf serum, and 10% dimethylsulfoxide and demonstrated 90 ± 1.7% viability after 3 mo frozen in liquid nitrogen. Freshly isolated and frozen thawed DiI- and Q-Tracker-labeled PGC repopulated stage 30 gonads after vascular transfer into ex ovo cultured embryos. The DiI-labeled cells repopulated gonads less frequently, with 36 ± 13.2% of gonads containing the DiI-labeled PGC, and 7 ± 3.8% of reinjected PGC reaching the gonads of positive embryos. The Q-tracker-labeled cells were detected more frequently in embryos, with 67 ± 21.1% having positive signals, and 44 ± 4.9% of reinjected Q-tracker-labeled PGC colonized the gonads of positive embryos. This study demonstrated the feasibility of using turkey PGC to archive turkey germplasm from different strains

  14. Long-term cultures of testicular biopsies from boys with cryptorchidism: effect of FSH and LH on the number of germ cells

    DEFF Research Database (Denmark)

    Larsen, Hans-Peter Ejler; Thorup, Jørgen; Skovgaard, Lene Theil;

    2002-01-01

    A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth.......A long-term culture system of testicular biopsies from boys with undescended testes was established to evaluate the effect of gonadotrophins on germ cell survival and growth....

  15. Mixed germ cell tumor metastatic to the skin: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Chang Ying-Hsu

    2010-03-01

    Full Text Available Abstract Background Testicular cancer is the most common cancer for males aged 15~35 years old. The initial presentation is typically an asymptomatic enlarged testicle. The retroperitoneum is the most common metastatic area. Other metastatic sites include the lung, liver, brain, adrenal glands, gastrointestinal tract and spleen. Skin metastasis is a rare event and frequently associated with poor prognosis. Case presentation A 19-year old male was diagnosed testicular mixed germ cell tumor with initial presentation of cutaneous metastasis at scalp and upper abdomen. After radical orchiectomy and four courses of cisplatin-based chemotherapy, the scalp and upper abdominal lesions regressed completely. The size of lung metastases remained unchanged. Conclusions For advanced stage testicular cancer, cisplatin-based chemotherapy is still effective to achieve partial response.

  16. Germ cell tumours of the ovary. A clinical study of 15 cases.

    Science.gov (United States)

    Friedman, M; Browde, S; Nissenbaum, M M

    1984-04-14

    Our experience with germ cell tumours of the ovary is reviewed. Over the last 10 years, 15 cases, representing 6,4% of all our referred patients with malignant ovarian tumours, have been analysed. The type of tumour, histological appearances, stage, treatment and results of treatment are presented. The tumour most commonly seen was the dysgerminoma, comprising 60% of all cases (9 patients). Multimodal treatment generally consisted of surgery and radiotherapy for dysgerminoma with the addition of chemotherapy for the non-dysgerminomas. Survival depends on the stage and histological appearances of the tumour. Patients in whom the disease is at advanced stages have a poor prognosis, irrespective of histological features. A general review of this subject is also given.

  17. Germ cell deficient (gcd) mouse as a model of premature ovarian failure.

    Science.gov (United States)

    Duncan, M; Cummings, L; Chada, K

    1993-08-01

    Premature ovarian failure (POF) in women is characterized as menopause commencing before age 35. Although some cases of POF appear to be inherited, no experimental animal models of familial POF are available. Recently a mouse mutation has been identified that results in infertility due to a lack of primordial germ cells arising in early embryonic development. It was observed that shortly after puberty, females homozygous for this mutation entered reproductive senescence as defined by high levels of circulating gonadotropins, inability to respond either hormonally or functionally to superovulation, and a disrupted estrous cycle. Also, the ovaries completely lacked developing follicles and the endometrium was inactive. However, these mice had undergone complete sexual development as determined by age of vaginal opening, mammary gland histology, and sexual behavior. Thus, these animals closely mimic familial premature ovarian failure and may be useful models for study of the pathogenesis and treatment of this condition.

  18. Primordial germ cells: the first cell lineage or the last cells standing?

    Science.gov (United States)

    Johnson, Andrew D; Alberio, Ramiro

    2015-08-15

    Embryos of many animal models express germ line determinants that suppress transcription and mediate early germ line commitment, which occurs before the somatic cell lineages are established. However, not all animals segregate their germ line in this manner. The 'last cell standing' model describes primordial germ cell (PGC) development in axolotls, in which PGCs are maintained by an extracellular signalling niche, and germ line commitment occurs after gastrulation. Here, we propose that this 'stochastic' mode of PGC specification is conserved in vertebrates, including non-rodent mammals. We postulate that early germ line segregation liberates genetic regulatory networks for somatic development to evolve, and that it therefore emerged repeatedly in the animal kingdom in response to natural selection. PMID:26286941

  19. [Biphasic pulmonary blastoma with germ cell differentiation: a challenge in diagnosis and treatment].

    Science.gov (United States)

    Teixeira, Alexandra; Vieira, Claúdia; Sousa, Nuno; Begonha, Rosa; Afonso, Mariana; Amaro, Teresina; Maurício, Joaquina

    2011-12-01

    Serviço de Oncologia Médica. Instituto Português de Oncologia Francisco Gentil. Porto. Portugal. A 27-year-old man, smoker, presented with three months history of fever. A left pulmonary mass inseparable from the heart was identified and serum alpha-fetoprotein was 4160 ng/ml. The morphologic aspects and immunohistochemistry of the biopsy specimen, in conjunction with the clinical findings were compatible with a diagnosis of pulmonary blastoma with germ cell differentiation. The tumour was considered unresectable. The patient was submitted to two cycles of primary chemotherapy with bleomycin, etoposide and cisplatin. Despite a reduction in serum alpha-fetoprotein, the tumor did not regress. Second line chemotherapy (with paclitaxel, ifosfamide and cisplatin) was instituted, but progressive disease was identified after 2 cycles. Six months after the diagnosis cerebral metastases were found and the patient died. This case illustrates a rare situation of difficult diagnosis and treatment.

  20. Germ Cell Testicular Cancer Incidence, Latitude and Sunlight Associations in the United States and Australia.

    Science.gov (United States)

    Biggar, Robert J; Baade, Peter D; Sun, Jiandong; Brandon, Lindsay E; Kimlin, Michael

    2016-09-01

    International patterns suggest germ cell testicular cancer (GCTC) incidence may be lower in lower latitudes. To investigate this possibility, we examined GCTC incidence by latitude (population centroid in 2000) for men ≥15 years within two reasonably homogeneous countries, the United States and Australia. In the United States, we examined age-adjusted incidence/latitude trends using data from states (2001-2010) and local-area registries (1980-2011). In Australia, we evaluated incidence/latitude trends in 61 Statistical Divisions (2000-2009). In U.S. White men (68 566 cases), state incidences increased by latitude, rising 5.74% (4.45-7.05%) per 5°North latitude increment. Similar trends were found for seminoma and nonseminoma subtypes (P distance from the equator, approximately 1% per degree within the range of latitudes studied. PMID:27400420

  1. Male germ cell apoptosis and epigenetic histone modification induced by Tripterygium wilfordii Hook F.

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    Ji Xiong

    Full Text Available Multiglycosides of Tripterygium wilfordii Hook f (GTW, a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on spermatogenesis, we administered 4 groups of 4-week-old male mice with different doses of GTW. We found a dose-dependent decrease in the number of germ cells after 40 days of GTW treatment, and an increase in apoptotic cells from the low-dose to the high-dose group. During this same period the dimethylated level of histone H3 lysine 9 (H3K9me2 in GTW-treated testes germ cells declined. Additionally, spermatogonial stem cells (SSCs from 6-day-old mice were isolated to evaluate the possible effect of GTW or triptolide on development of SSCs. We found a significantly higher incidence of apoptosis and lower dimethylation level of H3K9me2 in the SSCs of GTW or triptolide treatment than in controls. Thus, these data suggest that the GTW-induced apoptosis might be responsible for the fertility impairment in mice. This damage could be traced back to the early stages of spermatogenesis. GTW also affected the epigenetic modification of H3K9 in spermatogenesis. Molecular dynamics simulation suggested that triptolide and dimethylated or trimethylated H3K9 might have similar interaction mechanisms with EED (embryonic ectoderm development. These candidate activation mechanisms provide the first glimpse into the pathway of GTW-induced gonad toxicity, which is crucial for further research and clinical application.

  2. An alpha-crystallin protein cognate in germ cells of the moth, Plodia interpunctella.

    Science.gov (United States)

    Shirk, P D; Zimowska, G

    1997-02-01

    Previously we had reported the production of an antiserum to an antigen found primarily in germ cells of the Indianmeal moth, Plodia interpunctella (Zimowska et al., 1991). The antigen, molecular weight 25,000 kDa, and a related protein, molecular weight 21,000 kDa, co-purified with the follicular epithelium yolk protein. Antisera to the two proteins were raised, and they both reacted with the same four small polypeptides, which had molecular weights of 20,000, 21,000, 25,000 and 28,000 kDa, that were present in the eggs throughout embryogenesis. A 30 amino acid sequence of an internal fragment of the 25,000 kDa molecular weight polypeptide showed sequence similarity with the alpha-crystallin A chain polypeptides from the lenses of vertebrate eyes and, to a lesser extent, with small heat shock proteins. Based on the sequence similarity with the alpha-crystallins, we suggest that this family of polypeptides from the germ cells of this moth be considered as cognates of the alpha-crystallins, and the 25,000 molecular weight polypeptide described here be given the designation ac25. Using immuno-gold labeling with antiserum to ac25, the alpha-crystallins were shown to be distributed throughout the cytoplasm and nucleoplasm of the oocyte and nurse cells, but not present within yolk spheres or other organelles of the oocyte or nurse cells. Immunofluorescent staining of males showed antigenic material in the sperm bundles within the testes. Oenocytes of the pupal and adult stages also contained cross-reactive material.

  3. The genomic landscape of testicular germ cell tumours: from susceptibility to treatment.

    Science.gov (United States)

    Litchfield, Kevin; Levy, Max; Huddart, Robert A; Shipley, Janet; Turnbull, Clare

    2016-07-01

    The genomic landscape of testicular germ cell tumour (TGCT) can be summarized using four overarching hypotheses. Firstly, TGCT risk is dominated by inherited genetic factors, which determine nearly half of all disease risk and are highly polygenic in nature. Secondly KIT-KITLG signalling is currently the major pathway that is implicated in TGCT formation, both as a predisposition risk factor and a somatic driver event. Results from genome-wide association studies have also consistently suggested that other closely related pathways involved in male germ cell development and sex determination are associated with TGCT risk. Thirdly, the method of disease formation is unique, with tumours universally stemming from a noninvasive precursor lesion, probably of fetal origin, which lies dormant through childhood into adolescence and then eventually begins malignant growth in early adulthood. Formation of a 12p isochromosome, a hallmark of TGCT observed in nearly all tumours, is likely to be a key triggering event for malignant transformation. Finally, TGCT have been shown to have a distinctive somatic mutational profile, with a low rate of point mutations contrasted with frequent large-scale chromosomal gains. These four hypotheses by no means constitute a complete model that explains TGCT tumorigenesis, but advances in genomic technologies have enabled considerable progress in describing and understanding the disease. Further advancing our understanding of the genomic basis of TGCT offers a clear opportunity for clinical benefit in terms of preventing invasive cancer arising in young men, decreasing the burden of chemotherapy-related survivorship issues and reducing mortality in the minority of patients who have treatment-refractory disease. PMID:27296647

  4. Dicer is required for haploid male germ cell differentiation in mice.

    Directory of Open Access Journals (Sweden)

    Hanna M Korhonen

    Full Text Available BACKGROUND: The RNase III endonuclease Dicer is an important regulator of gene expression that processes microRNAs (miRNAs and small interfering RNAs (siRNAs. The best-characterized function of miRNAs is gene repression at the post-transcriptional level through the pairing with mRNAs of protein-encoding genes. Small RNAs can also act at the transcriptional level by controlling the epigenetic status of chromatin. Dicer and other mediators of small RNA pathways are present in mouse male germ cells, and several miRNAs and endogenous siRNAs are expressed in the testis, suggesting that Dicer-dependent small RNAs are involved in the control of the precisely timed and highly organised process of spermatogenesis. PRINCIPAL FINDINGS: Being interested in the Dicer-mediated functions during spermatogenesis, we have analysed here a male germ cell-specific Dicer1 knockout mouse model, in which the deletion of Dicer1 takes place during early postnatal development in spermatogonia. We found that Dicer1 knockout testes were reduced in size and spermatogenesis within the seminiferous tubules was disrupted. Dicer1 knockout epididymides contained very low number of mature sperm with pronounced morphological abnormalities. Spermatogonial differentiation appeared unaffected. However, the number of haploid cells was decreased in knockout testes, and an increased number of apoptotic spermatocytes was observed. The most prominent defects were found during late haploid differentiation, and Dicer was demonstrated to be critical for the normal organization of chromatin and nuclear shaping of elongating spermatids. CONCLUSIONS/SIGNIFICANCE: We demonstrate that Dicer and Dicer-dependent small RNAs are imperative regulators of haploid spermatid differentiation and essential for male fertility.

  5. 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

    2016-09-01

    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. PMID:27235586

  6. Association between polymorphisms in the aryl hydrocarbon receptor repressor gene and disseminated testicular germ cell cancer

    Directory of Open Access Journals (Sweden)

    Leon J. S. Brokken

    2013-02-01

    Full Text Available In the Western world, testicular germ cell cancer (TGCC is the most common malignancy of young men. The malignant transformation of germ cells is thought to be caused by developmental and hormonal disturbances, probably related to environmental and lifestyle factors because of rapidly increasing incidence of TGCC in some countries. Additionally, there is a strong genetic component that affects susceptibility. However, genetic polymorphisms that have been identified so far only partially explain the risk of TGCC. Many of the persistent environmental pollutants act through the aryl hydrocarbon receptor (AHR. AHR signalling pathway is known to interfere with reproductive hormone signalling, which is supposed to play a role in the pathogenesis and invasive progression of TGCC. The aim of the present study was to identify whether AHR-related polymorphisms were associated with risk as well as histological and clinical features of TGCC in 367 patients and 537 controls. Haplotype-tagging single nucleotide polymorphisms (SNPs were genotyped in genes encoding AHR and AHR repressor (AHRR. Binary logistic regression was used to calculate the risk of TGCC, nonseminoma versus seminoma, and metastasis versus localised disease.Four SNPs in AHRR demonstrated a significant allele association with risk to develop metastases (rs2466287: OR = 0.43, 95% CI 0.21-0.90; rs2672725: OR = 0.49, 95% CI: 0.25-0.94; rs6879758: OR = 0.27, 95% CI: 0.08-0.92; rs6896163: OR = 0.34, 95% CI: 0.12-0.98.This finding supports the hypothesis that compounds acting through AHR may play a role in the invasive progression of TGCC, either directly or through modification of reproductive hormone action.

  7. So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis.

    Science.gov (United States)

    Sano, K; Matsutani, M; Seto, T

    1989-06-01

    We investigated 110 cases of intracranial germ cell tumours (up to the end of 1986), 56% of which showed monotypic histological patterns and 44% were shown to be mixed tumours. All these cases underwent surgery followed by radiation and/or chemotherapy. All cases of choriocarcinoma and embryonal carcinoma died within 2 yr: cases of endodermal sinus tumour also showed poor results (4 yr survival rate was 12.5%). Mature teratoma had a 5 yr survival rate (5YSR) and a 10 yr survival rate (10YSR) of 78.3% each: immature teratoma showed a 5YSR of 44.9%. Two-cell pattern tumours (PTC) showed a 5YSR of 85.8% and a 10YSR of 82.4%. They (PTC) can be divided into two groups (i) germinoma and (ii) pinealoma of pineal parenchyma origin (pineocytoma with lymphocytic infiltration) on the basis of the difference in the tumour cell-stroma relationship and also placental alkaline phosphatase stain. In the pineal region, 70% of PTC belonged to the category of pinealoma and in the suprasellar region, 92% of PTC were germinoma. Germinoma showed a 5YSR of 91.4% and a 10YSR of 91.4%, whereas those of the pinealoma were 78.2% and 68.4% respectively. This suggests that the biological characteristics of germinoma and pinealoma may be different. All these results may bring into question the validity of the germ cell theory, since germinoma, which should be the most undifferentiated according to the theory, was the most benign and choriocarcinoma and endodermal sinus tumour, which should be the most differentiated, were the most malignant in the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2569683

  8. Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells.

    Directory of Open Access Journals (Sweden)

    Michelle L Churchman

    2011-07-01

    Full Text Available The mammalian Cdkn2a (Ink4a-Arf locus encodes two tumor suppressor proteins (p16(Ink4a and p19(Arf that respectively enforce the anti-proliferative functions of the retinoblastoma protein (Rb and the p53 transcription factor in response to oncogenic stress. Although p19(Arf is not normally detected in tissues of young adult mice, a notable exception occurs in the male germ line, where Arf is expressed in spermatogonia, but not in meiotic spermatocytes arising from them. Unlike other contexts in which the induction of Arf potently inhibits cell proliferation, expression of p19(Arf in spermatogonia does not interfere with mitotic cell division. Instead, inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production. Arf deficiency also causes premature, elevated, and persistent accumulation of the phosphorylated histone variant H2AX, reduces numbers of chromosome-associated complexes of Rad51 and Dmc1 recombinases during meiotic prophase, and yields incompletely synapsed autosomes during pachynema. Inactivation of Ink4a increases the fraction of spermatogonia in S-phase and restores sperm numbers in Ink4a-Arf doubly deficient mice but does not abrogate γ-H2AX accumulation in spermatocytes or p53-dependent apoptosis resulting from Arf inactivation. Thus, as opposed to its canonical role as a tumor suppressor in inducing p53-dependent senescence or apoptosis, Arf expression in spermatogonia instead initiates a salutary feed-forward program that prevents p53-dependent apoptosis, contributing to the survival of meiotic male germ cells.

  9. Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

    Science.gov (United States)

    Kulkarni, R P; Reynolds, K W; Newlands, E S; Dawson, P M; Makey, A R; Theodorou, N A; Bradley, J; Begent, R H; Rustin, G J; Bagshawe, K D

    1991-02-01

    Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

  10. The microRNA pathway controls germ cell proliferation and differentiation in C.elegans

    Institute of Scientific and Technical Information of China (English)

    Syed Irfan Ahmad Bukhari; Alejandro Vasquez-Rifo; Dominic Gagné; Eric R Paquet; Monique Zetka; Claude Robert; Jean-Yves Masson; Martin J Simard

    2012-01-01

    The discovery of the miRNA pathway revealed a new layer of molecular control of biological processes.To uncover new functions of this gene regulatory pathway,we undertook the characterization of the two miRNA-specific Argonaute proteins in Caenorhabditis elegans,ALG-1 and ALG-2.We first observed that the loss-of-function of alg-1 and alg-2 genes resulted in reduced progeny number.An extensive analysis of the germline of these mutants revealed a reduced mitotic region,indicating fewer proliferating germ cells.We also observed an early entry into meiosis in alg-1 and alg-2 mutant animals.We detected ALG-1 and ALG-2 protein expressions in the distal tip cell (DTC),a specialized cell located at the tip of both C.elegans gonadal arms that regulates mitosis-meiosis transition.Re-establishing the expression of alg-1 specifically in the DTC of mutant animals partially rescued the observed germline defects.Further analyses also support the implication of the miRNA pathway in gametogenesis.Interestingly,we observed that disruption of five miRNAs expressed in the DTC led to similar phenotypes.Finally,gene expression analysis of alg-1 mutant gonads suggests that the miRNA pathway is involved in the regulation of different pathways important for germline proliferation and differentiation.Collectively,our data indicate that the miRNA pathway plays a crucial role in the control of germ cell biogenesis in C.elegans.

  11. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

    Science.gov (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  12. EXAMINATION OF THE GERM CELL CHIMERA FORMING POTENTIAL OF MOUSE EMBRYONIC STEM CELLS

    Directory of Open Access Journals (Sweden)

    CÂRSTEA V. B

    2007-01-01

    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.

  13. EXAMINATION OF THE GERM CELL CHIMERA FORMING POTENTIAL OF MOUSE EMBRYONIC STEM CELLS

    Directory of Open Access Journals (Sweden)

    V.B. CÂRSTEA

    2013-12-01

    Full Text Available The aim of this study was to examine the factors, which influence the chimeraforming potential of mouse embryonic stem cells (ES cells. In our work, we examinethe chimera producing ability of R1 and R1/E mouse ES cell lines. We found that thepassage number affects chimera-forming capability of the ES cells. With theincreasing of the passage number, it could be getting less chimera animal, and onlythe R1/E ES cell line derived cells could contribute to the germ cells. At first, wecompared the marker of pluripotency using immunostaining and RT PCR, but wecould not find any difference between the R1 and R1/E cell in this way. Atchromosome analysis, we found, that the number of aneuploid cells, in R1 ES cellline, dramatically increased after 10 passages. We thought that the reason is thatduring the cell division Y chromosome could not arrange correctly between the twonewly derived progeny cells. To prove our conception, we made X and YchromosomeFISH analyses. We found, that the aneuploid R1 and R1/E ES cellscontain only one X and one Y chromosome, so not the loss of Y chromosome causethe problem at the germ cell formation. At last, we made the karyotypeanalysis of R1 and R1/E ES cells at different passages. The karyotype analysisdemonstrated that in the case of R1 ES cell line, the 41 and 42-chromosomecontaining cells hold trisomy. With the increasing of the passages number, thenumber of trisomy containing aneuploid cells increased. The aneuploid ES cells cancontribute to the different tissuses of chimera animals, but cannot form viable germcells.

  14. Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

    Science.gov (United States)

    Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

    2016-05-01

    Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement.

  15. Resistance Training Does Not Protect Against Increases in Plasma Cytokine Levels Among Germ Cell Cancer Patients During and After Chemotherapy

    DEFF Research Database (Denmark)

    Christensen, Jesper Frank; Tolver, Anders; Andersen, J.L.;

    2014-01-01

    Abstract Context: Testicular germ cell cancer (GCC) patients treated with cisplatin-etoposide-bleomycin chemotherapy (BEP) have excellent prognosis but have an increased risk of late-occurring morbidities, which may be associated with changes in the inflammatory profile. Objective: The objective ...

  16. GAGE cancer-germline antigens are recruited to the nuclear envelope by germ cell-less (GCL)

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Rösner, Heike I; Pedersen, Christina B;

    2012-01-01

    metazoan transcriptional regulator, Germ cell-less (GCL), as an interaction partner of GAGE12I. GCL directly binds LEM-domain proteins (LAP2β, emerin, MAN1) at the nuclear envelope, and we found that GAGE proteins were recruited to the nuclear envelope inner membrane by GCL. Based on yeast two...

  17. Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

    Science.gov (United States)

    Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

    2016-05-01

    Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement. PMID:26972155

  18. The International Testicular Cancer Linkage Consortium : A clinicopathologic descriptive analysis of 461 familial malignant testicular germ cell tumor kindred

    NARCIS (Netherlands)

    Mai, Phuong L.; Friedlander, Michael; Tucker, Kathy; Phillips, Kelly-Anne; Hogg, David; Jewett, Michael A. S.; Lohynska, Radka; Daugaard, Gedske; Richard, Stephane; Bonaiti-Pellie, Catherine; Heidenreich, Axel; Albers, Peter; Bodrogi, Istvan; Geczi, Lajos; Olah, Edith; Daly, Peter A.; Guilford, Parry; Fossa, Sophie D.; Heimdal, Ketil; Liubchenko, Ludmila; Tjulandin, Sergei A.; Stoll, Hans; Weber, Walter; Easton, Douglas F.; Dudakia, Darshna; Huddart, Robert; Stratton, Michael R.; Einhorn, Lawrence; Korde, Larissa; Nathanson, Katherine L.; Bishop, Timothy; Rapley, Elizabeth A.; Greene, Mark H.

    2010-01-01

    Objectives: Familial aggregation of testicular germ cell tumor (TGCT) has been reported, but it is unclear if familial TGCT represents a unique entity with distinct clinicopathologic characteristics. Here we describe a collection of familial TGCT cases from an international consortium, in an effort

  19. Application of seminal germ cell morphology and semen biochemistry in the diagnosis and management of azoospermic subjects

    Institute of Scientific and Technical Information of China (English)

    Somnath Roy; A. Banerjee; H.C. Pandey; G. Singh; G.L. Kumari

    2001-01-01

    To evaluate whether the study of seminal germ cell morphology (SGCM) and semen biochemistry could be fruitfully utilized for the diagnosis and management of azoospermic subjects. Methods: In the semen, mature and immature germ cells are contributed by the testes, 70% of glycerylphosphoryl choline (GPC) by the epididymis, fructose mostly or solely by the seminal vesicles and acid phosphate (ACP) by the prostate. In 16 normal volunteers, 12vasectomized subjects and 186 azoospermic subjects, these parameters have been studied and the data have been analyzed. Results: Both mature and immature germ cells are absent in the semen of vasectomized subjects as well as in obstructive azoospermia; GPC level is also significantly decreased in both these groups. In cases with non-obstructive azoospermia immature germ cells are present and seminal GPC, ACP and fructose levels are normal. The diagnosis of obstructive and non-obstructive azoospermia based on these parameters correlated well with "correct" testicular biopsy findings. In some cases of azoospermia due to hypospermatogenesis or spermatogenic developmental arrest, the SGCM studies were very helpful in objectively monitoring the response of the germinal tissue to specific treatments. Conclusion: SGCM and semen biochemical parameters are very valuable non-invasive markers for differentiating obstructive from non-obstructive azoospermia. The SGCM findings serve as a dependable non-invasive testicular marker with high predictive value.

  20. Low p21(Waf1/Cip1) protein level sensitizes testicular germ cell tumor cells to Fas-mediated apoptosis

    NARCIS (Netherlands)

    Spierings, DCJ; de Vries, EGE; Stel, AJ; Rietstap, NT; Vellenga, E; de Jong, S

    2004-01-01

    In the present study, we investigated the relation between p21 expression and the sensitivity of testicular germ cell tumor (TGCT) cells to apoptotic stimuli. Despite similar cisplatin-induced wild-type p53 accumulation, the TGCT cell lines Tera and Scha expressed low p21 protein and mRNA levels in

  1. Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study.

    NARCIS (Netherlands)

    M.R. van Dijk (Merel); E.W. Steyerberg (Ewout); S.P. Stenning; J.D.F. Habbema (Dik)

    2004-01-01

    textabstractBACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For this p

  2. 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

    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...

  3. Treatment Outcome and Quality of Life in Patients With Pediatric Extra-Cranial Germ Cell Tumors Previously Treated on Clinical Trial CCLG-GC-1979-01 or CCLG-GC-1989-01

    Science.gov (United States)

    2013-08-09

    Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Gastrointestinal Complications; Infertility; Long-term Effects Secondary to Cancer Therapy in Children; Neurotoxicity; Ovarian Cancer; Pulmonary Complications; Sexual Dysfunction; Urinary Complications

  4. Development of space-fertilized eggs and formation of primordial germ cells in the embryos of medaka fish

    Science.gov (United States)

    Ijiri, K.

    In the second International Microgravity Laboratory (IML-2) mission in 1994, four small Japanese killifish (Medaka, Oryzias latipes) made a space travel of 15 days aboard a space shuttle. These four adult Medaka fish successfully mated in space for the first time among vertebrate animals. Moreover, the eggs they laid developed normally, at least in their external appearance, hatching as fry (baby fish) in space. Fish mated and laid eggs every day during the first week. Near the end of the mission most of the eggs had a well-developed body with two pigmented eyes. In total, 43 eggs were laid (detected), out of which 8 fry hatched in space, as truly `space-originated' babies. A further 30 fry hatched within 3 days after landing. This is the normal hatching rate, compared with the ground-based data. Among the 8 space-originated fry, four were killed for histological sections, and germ cells at the gonadal region were counted for each fry. Their numbers were in the range of the germ cells of the normal control fry (ground-kept samples). Thus, as embryos developed normally in their external appearance, inside the embryos the formation of primordial germ cells took place normally in space, and their migration to the genital ridges was not hindered by microgravity. The two of the remaining space-originated fry have grown up and been creating their offspring in the laboratory. This proved that the primordial germ cells formed in space were also normal from a functional point of view. The four space-travelled adult fish re-started mating and laying eggs on the 7th day after landing and continued to do so every day afterward. Fertilization rate and hatchability of these eggs were as high as the eggs laid by the laboratory-kept fish. This fact implies that in gametogenesis of adult fish, there are no specific stages of germ cells extremely susceptible to microgravity.

  5. Transient and Stable GFP Expression in Germ Cells by the vasa Regulatory Sequences from the Red Seabream (Pagrus major

    Directory of Open Access Journals (Sweden)

    Fan Lin, Qinghua Liu, Mingyou Li, Zhendong Li, Ni Hong, Jun Li, Yunhan Hong

    2012-01-01

    Full Text Available Primordial germ cells (PGCs are the precursors of gametes responsible for genetic transmission to the next generation. They provide an ideal system for cryopreservation and restoration of biodiversity. Recently, considerable attention has been raised to visualize, isolate and transplant PGCs within and between species. In fish, stable PGC visualization in live embryo and individual has been limited to laboratory fish models such as medaka and zebrafish. One exception is the rainbow trout, which represents the only species with aquaculture importance and has GFP-labeled germ cells throughout development. PGCs can be transiently labeled by embryonic injection of mRNA containing green fluorescence protein gene (GFP and 3'-untranslated region (3'-UTR of a maternal germ gene such as vasa, nos1, etc. Stable PGC labeling can be achieved through production of transgenic animals by some transcriptional regulatory sequences from germ genes, such as the vasa promoter and 3'-UTR. In this study, we reported the functional analyses of the red seabream vasa (Pmvas regulatory sequences, using medaka as a model system. It was showed that injection of GFP-Pmvas3'UTR mRNA was able to label medaka PGCs during embryogenesis. Besides, we have constructed pPmvasGFP transgenic vector, and established a stable transgenic medaka line exhibiting GFP expression in germ cells including PGCs, mitotic and meiotic germ cells of both sexes, under control of the Pmvas transcriptional regulatory sequences. It is concluded that the Pmvas regulatory sequences examined in this study are sufficient for germ cell expression and labeling.

  6. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  7. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6–19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18–203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients

  8. Vitamin D Metabolism and Effects on Pluripotency Genes and Cell Differentiation in Testicular Germ Cell Tumors In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Martin Blomberg Jensen

    2012-10-01

    Full Text Available 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 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 TGCTs. VD metabolism diminished markedly during the malignant transformation from CIS to EC but was reestablished in differentiated components of nonseminomas, distinguished by coexpression of mesodermal markers and loss of OCT4. Subsequent in vitro studies confirmed that 1,25(OH2D3 (active VD downregulated NANOG and OCT4 through genomic VDR activation in EC-derived NTera2 cells and, to a lesser extent, in seminoma-derived TCam-2 cells, and up-regulated brachyury, SNAI1, osteocalcin, osteopontin, and fibroblast growth factor 23. To test for a possible therapeutic effect in vivo, NTera2 cells were xenografted into nude mice and treated with 1,25(OH2D3, which induced down-regulation of pluripotency factors but caused no significant reduction of tumor growth. During NTera2 tumor formation, down-regulation of VDR was observed, resulting in limited responsiveness to cholecalciferol and 1,25(OH2D3 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.

  9. Primordial germ cell-mediated chimera technology produces viable pure-line Houbara bustard offspring: potential for repopulating an endangered species.

    Directory of Open Access Journals (Sweden)

    Ulrich Wernery

    Full Text Available BACKGROUND: The Houbara bustard (Chlamydotis undulata is a wild seasonal breeding bird populating arid sandy semi-desert habitats in North Africa and the Middle East. Its population has declined drastically during the last two decades and it is classified as vulnerable. Captive breeding programmes have, hitherto, been unsuccessful in reviving population numbers and thus radical technological solutions are essential for the long term survival of this species. The purpose of this study was to investigate the use of primordial germ cell-mediated chimera technology to produce viable Houbara bustard offspring. METHODOLOGY/PRINCIPAL FINDINGS: Embryonic gonadal tissue was dissected from Houbara bustard embryos at eight days post-incubation. Subsequently, Houbara tissue containing gonadal primordial germ cells (gPGCs was injected into White Leghorn chicken (Gallus gallus domesticus embryos, producing 83/138 surviving male chimeric embryos, of which 35 chimeric roosters reached sexual maturity after 5 months. The incorporation and differentiation of Houbara gPGCs in chimeric chicken testis were assessed by PCR with Houbara-specific primers and 31.3% (5/16 gonads collected from the injected chicken embryos showed the presence of donor Houbara cells. A total of 302 semen samples from 34 chimeric roosters were analyzed and eight were confirmed as germline chimeras. Semen samples from these eight roosters were used to artificially inseminate three female Houbara bustards. Subsequently, 45 Houbara eggs were obtained and incubated, two of which were fertile. One egg hatched as a male live born Houbara; the other was female but died before hatching. Genotyping confirmed that the male chick was a pure-line Houbara derived from a chimeric rooster. CONCLUSION: This study demonstrates for the first time that Houbara gPGCs can migrate, differentiate and eventually give rise to functional sperm in the chimeric chicken testis. This approach may provide a promising

  10. Identification and characterization of 2 testicular germ cell markers, Glut3 and CyclinA2.

    Science.gov (United States)

    Howitt, Brooke E; Brooks, James D; Jones, Sunita; Higgins, John P T

    2013-10-01

    Testicular germ cell tumors (TGCT) are the most common type of testicular tumor and encompass different histologic types that greatly influence treatment and prognosis. Immunohistochemical studies may be required for accurate classification, particularly when these tumors present at extragonadal sites, and to aid in distinguishing histologic types. Traditional markers for identifying and distinguishing TGCT include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT3/4 and SALL4 has increased sensitivity for immunohistochemical detection of germ cell tumors. We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various TGCT. We also performed a search of the literature to identify less well-characterized markers. Glut3 and cyclinA2 showed promise as TGCT markers. Therefore, we evaluated expression of glut3 and cyclinA2 by immunohistochemistry using tissue microarrays (TMAs). Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2 and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All 20 of the embryonal carcinomas stained positively with cyclinA2, and 19 (95%) displayed strong nuclear staining for cyclinA2. Twenty of the 20 embryonal carcinomas stained for glut3 in a strong membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3. We also evaluated glut3 and cyclinA2 staining on a general TMA containing 486 samples representing 156 different tumors. CyclinA2 stained a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was rarely positive in other tumors; interestingly, most of these were of ovarian origin. We conclude that glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. Although cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if

  11. Separase phosphosite mutation leads to genome instability and primordial germ cell depletion during oogenesis.

    Directory of Open Access Journals (Sweden)

    Juan Xu

    Full Text Available To ensure equal chromosome segregation and the stability of the genome during cell division, Separase is strictly regulated primarily by Securin binding and inhibitory phosphorylation. By generating a mouse model that contained a mutation to the inhibitory phosphosite of Separase, we demonstrated that mice of both sexes are infertile. We showed that Separase deregulation leads to chromosome mis-segregation, genome instability, and eventually apoptosis of primordial germ cells (PGCs during embryonic oogenesis. Although the PGCs of mutant male mice were completely depleted, a population of PGCs from mutant females survived Separase deregulation. The surviving PGCs completed oogenesis but produced deficient initial follicles. These results indicate a sexual dimorphism effect on PGCs from Separase deregulation, which may be correlated with a gender-specific discrepancy of Securin. Our results reveal that Separase phospho-regulation is critical for genome stability in oogenesis. Furthermore, we provided the first evidence of a pre-zygotic mitotic chromosome segregation error resulting from Separase deregulation, whose sex-specific differences may be a reason for the sexual dimorphism of aneuploidy in gametogenesis.

  12. [Funcion sparing surgery in uro-oncology: germ cell tumors of the testis].

    Science.gov (United States)

    Catanzaro, Mario; Piva, Luigi; Torelli, Tullio; Biasoni, Davide; Stagni, Silvia; Milani, Angelo; Necchi, Andrea; Giannatempo, Patrizia; Nicolai, A; Salvioni, Roberto

    2012-01-01

    Surgery in germ cell tumors of the testis (TGT) may result in andrological disorders, both after orchiectomy and after retroperitoneal lymphadenectomy (RPLND). Bilateral orchiectomy suppresses both testicular functions: exocrine and endocrine. In selected cases with bilateral TGT (metachronous/synchronous), or in the case of TGT in monorchid patients, partial orchiectomy (enucleation of the tumor) can preserve both functions with a low risk of relapse in residual testicular parenchyma, in the absence of intraepithelial neoplasia (TIN). In cases of TIN and normal testosterone levels (80%), the fertility is maintained in 50% of patients. In these cases the use of radiotherapy on the residual testicular parenchyma can prevent the future development of invasive cancer, though compromising the hormonal function. The RPLND (open or laparoscopic) can produce major side effects, such as retrograde ejaculation. Knowledge of the adrenergic fiber retroperitoneal neuroanatomy enables to implement a "nerve sparing" surgery with an almost total reduction of this serious side effect, but that option is only available in few centers of excellence. Semen cryopreservation has become a common practice performed before any treatment that might impact on the andrological function of patients. PMID:23371266

  13. MRG-1 is required for genomic integrity in Caenorhabditis elegans germ cells

    Institute of Scientific and Technical Information of China (English)

    Jing Xu; Xiaojuan Sun; Yudong Jing; Mo Wang; Kai Liu; Youli Jian; Mei Yang; Zhukuan Cheng; Chonglin Yang

    2012-01-01

    During meiotic cell division,proper chromosome synapsis and accurate repair of DNA double strand breaks (DSBs) are required to maintain genomic integrity,loss of which leads to apoptosis or meiotic defects.The mechanisms underlying meiotic chromosome synapsis,DSB repair and apoptosis are not fully understood.Here,we report that the chromodomain-containiug protein MRG-1 is an important factor for genomic integrity in meiosis in Caenorhabditis elegans.Loss ofmrg-1 function resulted in a significant increase in germ cell apoptosis that was partially inhibited by mutations affecting DNA damage checkpoint genes.Consistently,mrg-1 mutant germ lines exhibited SPO-11-generated DSBs and elevated exogenous DNA damage-induced chromosome fragmentation at diakinesis.In addition,the excessive apoptosis in mrg-1 mutants was partially suppressed by loss of the synapsis checkpoint gene pch-2,and a significant number of meiotic nuclei accumulated at the leptotene/zygotene stages with an elevated level of H3K9me2 on the chromatin,which was similarly observed in mutants deficient in the synaptonemal complex,suggesting that the proper progression of chromosome synapsis is likely impaired in the absence of mrg-1.Altogether,these findings suggest that MRG-1 is critical for genomic integrity by promoting meiotic DSB repair and synapsis progression in meiosis.

  14. Germ cell nuclear factor directly represses the transcription of peroxisome proliferator-activated receptor delta gene

    Institute of Scientific and Technical Information of China (English)

    Chengqiang He; Naizheng Ding; Jie Kang

    2008-01-01

    Germ cell nuclear factor (GCNF) is a transcription factor that can repress gene transcription and plays an important role during spermatogenesis. Peroxisome proliferator-activated receptor delta (PPARδ) is a nuclear hormone receptor belonging to the steroid receptor superfamily.It can activate the expression of many genes,including those involved in lipid metabolism.In this report,we showed that GCNF specifically interacts with PPARδ promoter.Overexpression of GCNF in African green monkey SV40 transformed kidney fibroblast COS7 cells and mouse embryo fibroblast NIH 3T3 cells represses the activity of PPARδ promoter.The mutation of GCNF response element in PPARδ promoter relieves the repression in NIH 3T3 cells and mouse testis.Moreover,we showed that GCNF in nuclear extracts of mouse testis is able to bind to PPARδ promoter directly.We also found that GCNF and PPARδ mRNA were expressed with different patterns in mouse testis by in situ hybridization.These results suggested that GCNF might be a negative regulator of PPARδ gene expression through its direct interaction with PPARδ promoter in mouse testis.

  15. Neurl4 contributes to germ cell formation and integrity in Drosophila

    Directory of Open Access Journals (Sweden)

    Jennifer Jones

    2015-08-01

    Full Text Available Primordial germ cells (PGCs form at the posterior pole of the Drosophila embryo, and then migrate to their final destination in the gonad where they will produce eggs or sperm. Studies of the different stages in this process, including assembly of germ plasm in the oocyte during oogenesis, specification of a subset of syncytial embryonic nuclei as PGCs, and migration, have been informed by genetic analyses. Mutants have defined steps in the process, and the identities of the affected genes have suggested biochemical mechanisms. Here we describe a novel PGC phenotype. When Neurl4 activity is reduced, newly formed PGCs frequently adopt irregular shapes and appear to bud off vesicles. PGC number is also reduced, an effect exacerbated by a separate role for Neurl4 in germ plasm formation during oogenesis. Like its mammalian homolog, Drosophila Neurl4 protein is concentrated in centrosomes and downregulates centrosomal protein CP110. Reducing CP110 activity suppresses the abnormal PGC morphology of Neurl4 mutants. These results extend prior analyses of Neurl4 in cultured cells, revealing a heightened requirement for Neurl4 in germ-line cells in Drosophila.

  16. Mus308 Processes Oxygen and Nitrogen Ethylation DNA Damage in Germ Cells of Drosophila

    Directory of Open Access Journals (Sweden)

    Nancy Díaz-Valdés

    2010-01-01

    Full Text Available The D. melanogaster mus308 gene, highly conserved among higher eukaryotes, is implicated in the repair of cross-links and of O-ethylpyrimidine DNA damage, working in a DNA damage tolerance mechanism. However, despite its relevance, its possible role on the processing of different DNA ethylation damages is not clear. To obtain data on mutation frequency and on mutation spectra in mus308 deficient (mus308- conditions, the ethylating agent diethyl sulfate (DES was analysed in postmeiotic male germ cells. These data were compared with those corresponding to mus308 efficient conditions. Our results indicate that Mus308 is necessary for the processing of oxygen and N-ethylation damage, for the survival of fertilized eggs depending on the level of induced DNA damage, and for an influence of the DNA damage neighbouring sequence. These results support the role of mus308 in a tolerance mechanism linked to a translesion synthesis pathway and also to the alternative end-joinig system.

  17. Dynamic MR imaging of neurohypophyseal germ cell tumors for differential diagnosis of infundibular diseases

    International Nuclear Information System (INIS)

    To investigate the MR dynamic patterns of neurohypophyseal germ cell tumors (GCTs) for differential diagnosis of infundibular diseases affecting young people. Material and Methods: Eleven patients with neurohypophyseal GCTs underwent dynamic MR studies with T1-weighted spin-echo (SE) or turbo SE techniques. Other infundibular lesions, including adenohypophysitis (n=3), Langerhans' cell histiocytosis (LCH, n=2), and 1 hemangioblastoma from von Hippel-Lindau disease, were also evaluated. Serial images were obtained every 15 s (turbo SE) or 30 s (SE technique) for 240 s after rapid injection of contrast medium. The dynamic patterns were analyzed quantitatively with the contrast medium enhancement ratio. Results: On dynamic MR images, GCTs typically showed a gradual enhancement increase with a peak between 105 s and 180 s, while two showed a relatively rapid increase. LCH and hemangioblastoma showed a dynamic pattern similar to GCTs, while adenohypophysitis demonstrated a sharp rise and a steeper wash-out with an obvious peak before 90 s. Conclusion: Typical dynamic pattern of GCTs was the gradual enhancement increase without wash-out. Dynamic MR imaging can distinguish GCTs from adenohypophysitis, but is not useful for differentiation from LCH

  18. Dynamic MR imaging of neurohypophyseal germ cell tumors for differential diagnosis of infundibular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Liang, L.; Korogi, Y.; Sugahara, T.; Ikushima, I.; Shigematsu, Y.; Okuda, T.; Takahashi, M. [Kumamoto Univ. School of Medicine (Japan). Radiology Dept.

    2000-11-01

    To investigate the MR dynamic patterns of neurohypophyseal germ cell tumors (GCTs) for differential diagnosis of infundibular diseases affecting young people. Material and Methods: Eleven patients with neurohypophyseal GCTs underwent dynamic MR studies with T1-weighted spin-echo (SE) or turbo SE techniques. Other infundibular lesions, including adenohypophysitis (n=3), Langerhans' cell histiocytosis (LCH, n=2), and 1 hemangioblastoma from von Hippel-Lindau disease, were also evaluated. Serial images were obtained every 15 s (turbo SE) or 30 s (SE technique) for 240 s after rapid injection of contrast medium. The dynamic patterns were analyzed quantitatively with the contrast medium enhancement ratio. Results: On dynamic MR images, GCTs typically showed a gradual enhancement increase with a peak between 105 s and 180 s, while two showed a relatively rapid increase. LCH and hemangioblastoma showed a dynamic pattern similar to GCTs, while adenohypophysitis demonstrated a sharp rise and a steeper wash-out with an obvious peak before 90 s. Conclusion: Typical dynamic pattern of GCTs was the gradual enhancement increase without wash-out. Dynamic MR imaging can distinguish GCTs from adenohypophysitis, but is not useful for differentiation from LCH.

  19. Educational level of patients with germ cell tumor radiated in childhood

    International Nuclear Information System (INIS)

    In order to estimate the influence of radiotherapy on the intellectual development of children with brain tumor, we investigated the educational level of 21 patients with germ cell tumor who had undergone radiotherapy. They were divided into three groups in accordance with their age at the time of radiation; under school age group (under 6 years of age), elementary school age group (from 7 to 12 years of age), and junior high and high school age group (from 13 to 18 years of age). There were 2 cases in the under school age group, one of them graduated from high school and the other is presently a junior high school student. There were 5 cases in the elementary school age group. Three of these graduated from university, 1 is presently a university student and 1 is a high school student. There were 14 cases in the junior high and high school age group. Two of these are university students, 7 graduated from high school, 1 is presently a junior high school student, and 4 died because of tumor progression. The mean period of hospitalization of the patients who have been admitted to university was 63.0 days, and that of patients who have not been admitted university was 135 days. There is a statistical difference (p<0.05). It could be concluded that the period of hospitalization rather than radiotherapy seemed to influence the educational status of children with brain tumor. (author)

  20. DIFFERENTIAL SENSITIVITY OF MALE GERM CELLS TO MAINSTREAM AND SIDESTREAM TOBACCO SMOKE IN THE MOUSE

    Energy Technology Data Exchange (ETDEWEB)

    Polyzos, Aris; Schmid, Thomas Ernst; Pina-Guzman, Belem; Quintanilla-Vega, Betzabet; Marchetti, Francesco

    2009-03-13

    Cigarette smoking in men has been associated with increased chromosomal abnormalities in sperm and with increased risks for spontaneous abortions, birth defects and neonatal death. Little is known, however, about the reproductive consequences of paternal exposure to second-hand smoke. We used a mouse model to investigate the effects of paternal exposure to sidestream (SS) smoke, the main constituent of second-hand smoke, on the genetic integrity and function of sperm, and to determine whether male germ cells were equally sensitive to mainstream (MS) and SS smoke. A series of sperm DNA quality and reproductive endpoints were investigated after exposing male mice for two weeks to MS or SS smoke. Our results indicated that: (i) only SS smoke significantly affected sperm motility; (ii) only MS smoke induced DNA strand breaks in sperm; (iii) both MS and SS smoke increased sperm chromatin structure abnormalities; and (iv) MS smoke affected both fertilization and the rate of early embryonic development, while SS smoke affected fertilization only. These results show that MS and SS smoke have differential effects on the genetic integrity and function of sperm and provide further evidence that male exposure to second-hand smoke, as well as direct cigarette smoke, may diminish a couple's chance for a successful pregnancy and the birth of a healthy baby.

  1. Conservation of Poultry Germplasm Through Cryopreservation of Primordial Germ Cells (PGCs

    Directory of Open Access Journals (Sweden)

    A R Setioko

    2008-06-01

    Full Text Available Indonesia has abundantly available genetic potential of local poultry that needs to be conserved for future use of poultry development. Live conservation of poultry, both in-situ and ex-situ, would be very expensive and has a risk of mortality due to diseases such as avian influenza. Cryopreservation of Primordial Germ Cells (PGCs, which are progenitor of eggs and spermatozoa, provides an alternative way to preserve both male and female genetic materials in poultry. PGCs in poultry can be specifically harvested from blatoderm or blood embryo, and preserved in a liquid nitrogen similar to sperm, ovum and embryo in large ruminant. Technique for producing germline chimeric chicken has been established by transferring PGCs into the circulated blood embryo where the original PGCs have been removed or inactivated. Mating of germline chimeras yields offsprings that are derived entirely from the donor stock. Conservation of genetic materials of Indonesian indigenous poultry through preservation of PGCs could be used for future poultry improvement.

  2. Effect of kinase-negative EGFR gene on differentiation of embryonic germ cell line EG4

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    EG4 cells derived from primordial germ cells (PGCs) of 10.5 d post coitum 129/svJ mouse embryos can be used as a model system for in vitro differentiation study due to their pluripotential development ability. EG4 cell lines with stable expression of kinase-negative EGFR cDNA, designated EG4-EGFRd, were generated by gene transfection.We found that: (i) EG4-EGFRd cells share the similar morphology and growing character with wildtype cells that can maintain undifferentiated state in long term culture. ( ii )Treatment of EG4 cells with RA resulted in differentiation of adipocyte, while in mutant clones of EG4-EGFRd, adipocytes were sparse or absent under the same condition, indicating the role of EGFR expressed during adipocyte development.(iii) Histological analysis showed that predominant tissues in teratocarcinomas derived from EG4-EGFRd cells and wildtype cells are different. A large amount of undifferentiated cells was present in those coming from mutant cell clones. In addition some cardiac and skeletal muscles are prominently differentiated cell types. EG4 wildtype cells produced multiple differentiated cell types of three primary germ layers such as cartilage, epithelia and neural tube. These studies suggested that EGFR-dependent differentiation was inhibited in kinase-negative EG4 cells.``

  3. The mechanism for primordial germ-cell migration is conserved between Japanese eel and zebrafish.

    Directory of Open Access Journals (Sweden)

    Taiju Saito

    Full Text Available Primordial germ cells (PGCs are segregated and specified from somatic cells during early development. These cells arise elsewhere and have to migrate across the embryo to reach developing gonadal precursors. Several molecules associated with PGC migration (i.e. dead-end, nanos1, and cxcr4 are highly conserved across phylum boundaries. However, since cell migration is a complicated process that is regulated spatially and temporally by multiple adaptors and signal effectors, the process is unlikely to be explained by these known genes only. Indeed, it has been shown that there are variations in PGC migration pattern during development among teleost species. However, it is still unclear whether the actual mechanism of PGC migration is conserved among species. In this study, we studied the migration of PGCs in Japanese eel (Anguilla japonica embryos and tested the migration mechanism between Japanese eel and zebrafish (Danio rerio for conservation, by transplanting eel PGCs into zebrafish embryos. The experiments showed that eel PGCs can migrate toward the gonadal region of zebrafish embryos along with endogenous PGCs, even though the migration patterns, behaviors, and settlements of PGCs are somewhat different between these species. Our results demonstrate that the migration mechanism of PGCs during embryonic development is highly conserved between these two distantly related species (belonging to different teleost orders.

  4. Hypoxia impairs primordial germ cell migration in zebrafish (Danio rerio embryos.

    Directory of Open Access Journals (Sweden)

    Kwok Hong Lo

    Full Text Available BACKGROUND: As a global environmental concern, hypoxia is known to be associated with many biological and physiological impairments in aquatic ecosystems. Previous studies have mainly focused on the effect of hypoxia in adult animals. However, the effect of hypoxia and the underlying mechanism of how hypoxia affects embryonic development of aquatic animals remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In the current study, the effect of hypoxia on primordial germ cell (PGC migration in zebrafish embryos was investigated. Hypoxic embryos showed PGC migration defect as indicated by the presence of mis-migrated ectopic PGCs. Insulin-like growth factor (IGF signaling is required for embryonic germ line development. Using real-time PCR, we found that the mRNA expression levels of insulin-like growth factor binding protein (IGFBP-1, an inhibitor of IGF bioactivity, were significantly increased in hypoxic embryos. Morpholino knockdown of IGFBP-1 rescued the PGC migration defect phenotype in hypoxic embryos, suggesting the role of IGFBP-1 in inducing PGC mis-migration. CONCLUSIONS/SIGNIFICANCE: This study provides novel evidence that hypoxia disrupts PGC migration during embryonic development in fish. IGF signaling is shown to be one of the possible mechanisms for the causal link between hypoxia and PGC migration. We propose that hypoxia causes PGC migration defect by inhibiting IGF signaling through the induction of IGFBP-1.

  5. Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.

    Science.gov (United States)

    Chatfield, Jodie; O'Reilly, Marie-Anne; Bachvarova, Rosemary F; Ferjentsik, Zoltan; Redwood, Catherine; Walmsley, Maggie; Patient, Roger; Loose, Mathew; Johnson, Andrew D

    2014-06-01

    A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates.

  6. The migrations of Drosophila muscle founders and primordial germ cells are interdependent.

    Science.gov (United States)

    Stepanik, Vincent; Dunipace, Leslie; Bae, Young-Kyung; Macabenta, Frank; Sun, Jingjing; Trisnadi, Nathanie; Stathopoulos, Angelike

    2016-09-01

    Caudal visceral mesoderm (CVM) cells migrate from posterior to anterior of the Drosophila embryo as two bilateral streams of cells to support the specification of longitudinal muscles along the midgut. To accomplish this long-distance migration, CVM cells receive input from their environment, but little is known about how this collective cell migration is regulated. In a screen we found that wunen mutants exhibit CVM cell migration defects. Wunens are lipid phosphate phosphatases known to regulate the directional migration of primordial germ cells (PGCs). PGC and CVM cell types interact while PGCs are en route to the somatic gonadal mesoderm, and previous studies have shown that CVM impacts PGC migration. In turn, we found here that CVM cells exhibit an affinity for PGCs, localizing to the position of PGCs whether mislocalized or trapped in the endoderm. In the absence of PGCs, CVM cells exhibit subtle changes, including more cohesive movement of the migrating collective, and an increased number of longitudinal muscles is found at anterior sections of the larval midgut. These data demonstrate that PGC and CVM cell migrations are interdependent and suggest that distinct migrating cell types can coordinately influence each other to promote effective cell migration during development. PMID:27578182

  7. Zebrafish vasa is required for germ-cell differentiation and maintenance.

    Science.gov (United States)

    Hartung, Odelya; Forbes, Meredyth M; Marlow, Florence L

    2014-10-01

    Vasa is a universal marker of the germ line in animals, yet mutations disrupting vasa cause sexually dimorphic infertility, with impaired development of the ovary in some animals and the testis in others. The basis for this sexually dimorphic requirement for Vasa is not clear; in most animals examined, both the male and female gonad express vasa throughout the life of the germ line. Here we characterized a loss-of-function mutation disrupting zebrafish vasa. We show that maternally provided Vasa is stable through the first ten days of development in zebrafish, and thus likely fulfills any early roles for Vasa during germ-line specification, migration, survival, and maintenance. Although zygotic Vasa is not essential for the development of juvenile gonads, vasa mutants develop exclusively as sterile males. Furthermore, phenotypes of vasa;p53 compound mutants are indistinguishable from those of vasa mutants, therefore the failure of vasa mutants to differentiate as females and to support germ-cell development in the testis is not due to p53-mediated apoptosis. Instead, we found that failure to progress beyond the pachytene stage of meiosis causes the loss of germ-line stem cells, leaving empty somatic tubules. Our studies provide insight into the function of zebrafish vasa during female meiosis, differentiation, and maintenance of germ-line stem cells.

  8. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells

    OpenAIRE

    Mark E Gill; Hu, Yueh-Chiang; Lin, Yanfeng; David C Page

    2011-01-01

    Mammalian oocytes and spermatozoa derive from fetal cells shared by the sexes. These primordial germ cells (PGCs) migrate to the developing somatic gonad, giving rise to oocytes or spermatozoa. These opposing sexual fates are determined not by the PGCs’ own sex chromosome constitution (XX or XY), but by the sexual identity of the fetal gonad that they enter. We asked whether PGCs undergo a developmental transition that enables them to respond to feminizing or masculinizing cues from fetal ova...

  9. Localization study of the primordial germ cells in embryos of the Japanese Quail by means of ultraviolet irradiation

    International Nuclear Information System (INIS)

    In the Japanese quail embryo at the stage of 6 pairs of somites, ultraviolet irradiation of the extraembryonic crescent-shaped area anterior to the level of the first somites does not lead to total sterilization of the developing gonads. There are always subsisting primordial germ cells which apparently can restore the population of gonocytes. On the contrary, complete sterilization can be obtained by irradiating the area extending posteriorly to the level of the Hensen node

  10. Long-term Disease Free and Successful Pregnancy in a Woman with Gonadal Dysgenesis and Malignant Germ Cell Tumor

    OpenAIRE

    Azamsadat Mousavi; Mitra Gilani; Shirin Goodarzi; Ensieh Tehraninejad; Hayedeh Haeri

    2012-01-01

    Objective: To report a case of long-term disease free and successful pregnancy after fertility sparing staging surgery with adjuvant chemotherapy in a 46,Xy gonadal dysgenetic with malignant germ cell tumor.Materials and methods: A case report from a university hospital about a 19-year-old female with 46,XY karyotype ( Swyer syndrome). The patient underwent bilateral gonadectomy and staging with uterus preservation. Six course adjuvant chemotherapy with VBP (Vinblastin, Bleomycin, Cisplatin) ...

  11. Bleomycin induced flagellate erythema in a patient with thalamic mixed germ cell tumour: Report of a rare adverse effect

    OpenAIRE

    Ahitagni Biswas; Pramod Kumar Julka

    2016-01-01

    Bleomycin induced flagellate dermatitis is an uncommon and unique adverse effect. With the declining use of bleomycin, this complication is becoming increasingly infrequent in day-to-day clinical practice. We herein describe a case of a 13 year old male patient with left thalamic mixed germ cell tumour treated by multimodality approach, who developed flagellate erythema after two cycles of combination chemotherapy with bleomycin, etoposide and cisplatin (BEP). This brief report highlights the...

  12. From primordial germ cells to primordial follicles: a review and visual representation of early ovarian development in mice

    OpenAIRE

    Wear, Hannah M.; McPike, Matthew J; Watanabe, Karen H.

    2016-01-01

    Background Normal development of reproductive organs is crucial for successful reproduction. In mice the early ovarian developmental process occurs during the embryonic and postnatal period and is regulated through a series of molecular signaling events. Early ovarian development in mice is a seventeen-day process that begins with the rise of six primordial germ cells on embryonic day five (E5) and ends with the formation of primordial follicles on postnatal day two (P2). Results We reviewed ...

  13. Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell apoptosis by Ras/MAPK signaling.

    Directory of Open Access Journals (Sweden)

    Rachael Rutkowski

    2011-08-01

    Full Text Available Maintaining genome stability in the germline is thought to be an evolutionarily ancient role of the p53 family. The sole Caenorhabditis elegans p53 family member CEP-1 is required for apoptosis induction in meiotic, late-stage pachytene germ cells in response to DNA damage and meiotic recombination failure. In an unbiased genetic screen for negative regulators of CEP-1, we found that increased activation of the C. elegans ERK orthologue MPK-1, resulting from either loss of the lip-1 phosphatase or activation of let-60 Ras, results in enhanced cep-1-dependent DNA damage induced apoptosis. We further show that MPK-1 is required for DNA damage-induced germ cell apoptosis. We provide evidence that MPK-1 signaling regulates the apoptotic competency of germ cells by restricting CEP-1 protein expression to cells in late pachytene. Restricting CEP-1 expression to cells in late pachytene is thought to ensure that apoptosis doesn't occur in earlier-stage cells where meiotic recombination occurs. MPK-1 signaling regulates CEP-1 expression in part by regulating the levels of GLD-1, a translational repressor of CEP-1, but also via a GLD-1-independent mechanism. In addition, we show that MPK-1 is phosphorylated and activated upon ionising radiation (IR in late pachytene germ cells and that MPK-1-dependent CEP-1 activation may be in part direct, as these two proteins interact in a yeast two-hybrid assay. In summary, we report our novel finding that MAP kinase signaling controls CEP-1-dependent apoptosis by several different pathways that converge on CEP-1. Since apoptosis is also restricted to pachytene stage cells in mammalian germlines, analogous mechanisms regulating p53 family members are likely to be conserved throughout evolution.

  14. Identifying subgroups among poor prognosis patients with nonseminomatous germ cell cancer by tree modelling: a validation study.

    OpenAIRE

    Dijk, Merel; Steyerberg, Ewout; Stenning, S. P.; Habbema, Dik

    2004-01-01

    textabstractBACKGROUND: In order to target intensive treatment strategies for poor prognosis patients with non-seminomatous germ cell cancer, those with the poorest prognosis should be identified. These patients might profit most from more intensive treatment strategies. For this purpose, a regression tree was previously developed on 332 patients. We aimed to evaluate the performance and structure of this tree. PATIENTS AND METHODS: The previously developed tree was applied to 456 patients wi...

  15. Temporal transcriptional profiling of somatic and germ cells reveals biased lineage priming of sexual fate in the fetal mouse gonad.

    Directory of Open Access Journals (Sweden)

    Samantha A Jameson

    Full Text Available The divergence of distinct cell populations from multipotent progenitors is poorly understood, particularly in vivo. The gonad is an ideal place to study this process, because it originates as a bipotential primordium where multiple distinct lineages acquire sex-specific fates as the organ differentiates as a testis or an ovary. To gain a more detailed understanding of the process of gonadal differentiation at the level of the individual cell populations, we conducted microarrays on sorted cells from XX and XY mouse gonads at three time points spanning the period when the gonadal cells transition from sexually undifferentiated progenitors to their respective sex-specific fates. We analyzed supporting cells, interstitial/stromal cells, germ cells, and endothelial cells. This work identified genes specifically depleted and enriched in each lineage as it underwent sex-specific differentiation. We determined that the sexually undifferentiated germ cell and supporting cell progenitors showed lineage priming. We found that germ cell progenitors were primed with a bias toward the male fate. In contrast, supporting cells were primed with a female bias, indicative of the robust repression program involved in the commitment to XY supporting cell fate. This study provides a molecular explanation reconciling the female default and balanced models of sex determination and represents a rich resource for the field. More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates.

  16. Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations.

    Science.gov (United States)

    Sakaguchi, Aisa; Sarkies, Peter; Simon, Matt; Doebley, Anna-Lisa; Goldstein, Leonard D; Hedges, Ashley; Ikegami, Kohta; Alvares, Stacy M; Yang, Liwei; LaRocque, Jeannine R; Hall, Julie; Miska, Eric A; Ahmed, Shawn

    2014-10-14

    Germ cells are maintained in a pristine non-aging state as they proliferate over generations. Here, we show that a novel function of the Caenorhabditis elegans RNA interference proteins RNAi spreading defective (RSD)-2 and RSD-6 is to promote germ cell immortality at high temperature. rsd mutants cultured at high temperatures became progressively sterile and displayed loss of small interfering RNAs (siRNAs) that target spermatogenesis genes, simple repeats, and transposons. Desilencing of spermatogenesis genes occurred in late-generation rsd mutants, although defective spermatogenesis was insufficient to explain the majority of sterility. Increased expression of repetitive loci occurred in both germ and somatic cells of late-generation rsd mutant adults, suggesting that desilencing of many heterochromatic segments of the genome contributes to sterility. Nuclear RNAi defective (NRDE)-2 promotes nuclear silencing in response to exogenous double-stranded RNA, and our data imply that RSD-2, RSD-6, and NRDE-2 function in a common transgenerational nuclear silencing pathway that responds to endogenous siRNAs. We propose that RSD-2 and RSD-6 promote germ cell immortality at stressful temperatures by maintaining transgenerational epigenetic inheritance of endogenous siRNA populations that promote genome silencing. PMID:25258416

  17. Restricted distribution of mrg-1 mRNA in C. elegans primordial germ cells through germ granule-independent regulation.

    Science.gov (United States)

    Miwa, Takashi; Takasaki, Teruaki; Inoue, Kunio; Sakamoto, Hiroshi

    2015-11-01

    The chromodomain protein MRG-1 is an essential maternal factor for proper germline development that protects germ cells from cell death in C. elegans. Unlike germ granules, which are exclusively segregated to the germline blastomeres at each cell division from the first cleavage of the embryo, MRG-1 is abundant in all cells in early embryos and is then gradually restricted to the primordial germ cells (PGCs) by the morphogenesis stage. Here, we show that this characteristic spatiotemporal expression pattern is dictated by the mrg-1 3'UTR and is differentially regulated at the RNA level between germline and somatic cells. Asymmetric segregation of germ granules is not necessary to localize MRG-1 to the PGCs. We found that MES-4, an essential chromatin regulator in germ cells, also accumulates in the PGCs in a germ granule-independent manner. We propose that C.elegans PGCs have a novel mechanism to accumulate at least some chromatin-associated proteins that are essential for germline immortality. PMID:26537333

  18. Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells.

    Directory of Open Access Journals (Sweden)

    Rita L Peruquetti

    Full Text Available Spermatogenesis is a complex differentiation process that involves genetic and epigenetic regulation, sophisticated hormonal control, and extensive structural changes in male germ cells. RNA nuclear and cytoplasmic bodies appear to be critical for the progress of spermatogenesis. The chromatoid body (CB is a cytoplasmic organelle playing an important role in RNA post-transcriptional and translation regulation during the late steps of germ cell differentiation. The CB is also important for fertility determination since mutations of genes encoding its components cause infertility by spermatogenesis arrest. Targeted ablation of the Bmal1 and Clock genes, which encode central regulators of the circadian clock also result in fertility defects caused by problems other than spermatogenesis alterations. We show that the circadian proteins CLOCK and BMAL1 are localized in the CB in a stage-specific manner of germ cells. Both BMAL1 and CLOCK proteins physically interact with the ATP-dependent DEAD-box RNA helicase MVH (mouse VASA homolog, a hallmark component of the CB. BMAL1 is differentially expressed during the spermatogenic cycle of seminiferous tubules, and Bmal1 and Clock deficient mice display significant CB morphological alterations due to BMAL1 ablation or low expression. These findings suggest that both BMAL1 and CLOCK contribute to CB assembly and physiology, raising questions on the role of the circadian clock in reproduction and on the molecular function that CLOCK and BMAL1 could potentially have in the CB assembly and physiology.

  19. 鱼类原始生殖细胞与鱼类性别分化的关系%Role of Fish Primordial Germ Cells in Sex Differentiation

    Institute of Scientific and Technical Information of China (English)

    詹冰津; 池丽影; 张军玲; 张会会

    2013-01-01

    In fish sex differentiation, the proliferation ways of primordial germ cells in male and female are different, and some fish which lack primordial germ cells will develop into a single male phenotype. In this process, sexual dimorphic expression of a splice variant of germ cell specific gene vasa is close with primordial germ cell differentiation.%在鱼类的性别分化中,原始生殖细胞在雌雄二性中的增殖方式不同,而且在部分鱼类中原始生殖细胞的缺失能导致其发育为单一雄性表型.在此过程中,生殖细胞的特有基因vasa的剪接变体的二态性分布与鱼类原始生殖细胞的分化关系密切.

  20. Complications of the post-chemotherapy resection of retroperitoneal residual tumour mass in patients with non-seminomatous testicular germ cell tumours

    NARCIS (Netherlands)

    Gels, ME; Nijboer, AP; Hoekstra, HJ; Sleijfer, DT; Molenaar, WM; Plukker, JT; Droste, JHJ; Schraffordt Koops, H.

    1997-01-01

    Objective To evaluate the resection of the retroperitoneal residual tumour mass (RRTM) for histological examination after chemotherapy in patients with disseminated non-seminomatous testicular germ cell tumours (NSTGCTs), with particular attention to surgical morbidity. Patients and methods From 197

  1. A novel puf-A gene predicted from evolutionary analysis is involved in the development of eyes and primordial germ-cells.

    Directory of Open Access Journals (Sweden)

    Ming-Wei Kuo

    Full Text Available Although the human genome project has been completed for some time, the issue of the number of transcribed genes with identifiable biological functions remains unresolved. We used zebrafish as a model organism to study the functions of Ka/Ks-predicted novel human exons, which were identified from a comparative evolutionary genomics analysis.In this study, a novel gene, designated as puf-A, was cloned and functionally characterized, and its homologs in zebrafish, mouse, and human were identified as one of the three homolog clusters which were consisted of 14 related proteins with Puf repeats. Computer modeling of human Puf-A structure and a pull-down assay for interactions with RNA targets predicted that it was a RNA-binding protein. Specifically, Puf-A contained a special six Puf-repeat domain, which constituted a unique superhelix half doughnut-shaped Puf domain with a topology similar to, but different from the conventional eight-repeat Pumilio domain. Puf-A transcripts were uniformly distributed in early embryos, but became restricted primarily to eyes and ovaries at a later stage of development. In mice, puf-A expression was detected primarily in retinal ganglion and pigmented cells. Knockdown of puf-A in zebrafish embryos resulted in microphthalmia, a small head, and abnormal primordial germ-cell (PGC migration. The latter was confirmed by microinjecting into embryos puf-A siRNA containing nanos 3' UTR that expressed in PGC only. The importance of Puf-A in the maturation of germline stem cells was also implicated by its unique expression in the most primitive follicles (stage I in adult ovaries, followed by a sharp decline of expression in later stages of folliculogenesis. Taken together, our study shows that puf-A plays an important role not only in eye development, but also in PGC migration and the specification of germ cell lineage. These studies represent an exemplary implementation of a unique platform to uncover unknown function(s of

  2. 51. Mutagenicity Study of Cyclophoshpamide on Human Sperm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Whether Cyclophoshpamide(CP) has mutagenicity on germ cell or not is paid close attention to. This paper studied the mutagenicity of CP on germ cell by adopting human sperm chromosome and micronuclus in two-cell embryo. Semen samples obtained from healthy male were liquefied、dealed with Ca2+, and exposed to four

  3. MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Kock, Kirsten; Nielsen, Ole;

    2007-01-01

    BACKGROUND: Cancer/testis antigens (CTAs) are expressed in several cancers and during normal adult male germ cell differentiation. Little is known about their role in fetal development of human germ cells. METHODS: We examined expression of the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads...... by single and double immunohistochemical staining. RESULTS: We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ...... cells and the staining intensity of all three CTAs peaked during the second trimester and gradually decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1 expression terminated around birth, whereas NY-ESO-1 expression persisted through the neonatal stage and GAGE expression...

  4. Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer

    DEFF Research Database (Denmark)

    de Wit, Ronald; Skoneczna, Iwona; Daugaard, Gedske;

    2012-01-01

    To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC).......To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC)....

  5. Localization of early germ cells in a stony coral, Euphyllia ancora: potential implications for a germline stem cell system in coral gametogenesis

    Science.gov (United States)

    Shikina, Shinya; Chung, Yi-Jou; Wang, Hsiang-Ming; Chiu, Yi-Ling; Shao, Zih-Fang; Lee, Yan-Horn; Chang, Ching-Fong

    2015-06-01

    Most corals exhibit annual or multiple gametogenic cycles. Thus far, coral gametogenesis has been studied in many species and locations during the past three decades; however, currently, only a few papers exist that describe the origin of germ cells, such as germline stem cells (GSCs), which support the continuous production of gametes in every reproductive cycle. To address this issue, in this study, we focused on and identified piwi gene, which has been used as a marker of germline cells, including GSCs, in various metazoans, in a scleractinian coral, Euphyllia ancora. Reverse-transcription PCR and Western blotting analyses revealed that E. ancora piwi-like ( Eapiwi) is expressed in mesentery tissues where the sites of gametogenesis are located for both sexes. Immunohistochemistry with a specific antibody against Eapiwi revealed strong immunoreactivity in the spermatogonia in males and in the oogonia and early oocytes in females, demonstrating that Eapiwi could be used as an early germ cell marker in E. ancora. Subsequent immunohistochemical analyses regarding the spatial and temporal distribution patterns of early germ cells in mesentery tissues revealed that early germ cells were present throughout the year in the mesentery tissue we examined, regardless of the sexual reproductive cycle. In particular, small numbers of early germ cells were observed in specific sites of mesentery tissues with fully matured gonads in both sexes. These early germ cells were not released together with mature gametes during the spawning period and remained in the mesentery tissues. These results suggested that these early germ cells most likely serve as a reservoir of germline cells and that some of these cells would produce differentiated germ cells for the upcoming sexual reproduction period; hence, these cells would function as GSCs. Our data provide new information for understanding continuous gamete production in corals.

  6. Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

    Directory of Open Access Journals (Sweden)

    Ataergin S

    2007-01-01

    Full Text Available Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients′ outcome. Statistical Analysis :0 Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P < 0.001 and disease-free survival rates were 83%, 34% and 7% ( P < 0.001 in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P < 0.001, the initial stage of disease ( P < 0.001, the initial serum AFP level (p: 0.001, the initial β -HCG level (p: 0.0048, the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0

  7. Benzo(a)pyrene Induced p53 Mediated Male Germ Cell Apoptosis: Synergistic Protective Effects of Curcumin and Resveratrol.

    Science.gov (United States)

    Banerjee, Bhaswati; Chakraborty, Supriya; Ghosh, Debidas; Raha, Sanghamitra; Sen, Parimal C; Jana, Kuladip

    2016-01-01

    Benzo(a)pyrene (B(a)P) is an environmental toxicant that induces male germ cell apoptosis. Curcumin and resveratrol are phytochemicals with cytoprotective and anti-oxidative properties. At the same time resveratrol is also a natural Aryl hydrocarbon Receptor (AhR) antagonist. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted the synergistic protective effect of curcumin and resveratrol against B(a)P induced p53 mediated germ cell apoptosis. Curcumin-resveratrol significantly prevented B(a)P induced decrease in sperm cell count and motility, as well as increased serum testosterone level. Curcumin-resveratrol co-treatment actively protected B(a)P induced testicular germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3, 8 and 9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, and Apaf1. B(a)P induced testicular reactive oxygen species (ROS) generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 (Cytochrome P4501A1) expression. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ

  8. Sexual Fate Change of XX Germ Cells Caused by the Deletion of SMAD4 and STRA8 Independent of Somatic Sex Reprogramming.

    Science.gov (United States)

    Wu, Quan; Fukuda, Kurumi; Kato, Yuzuru; Zhou, Zhi; Deng, Chu-Xia; Saga, Yumiko

    2016-09-01

    The differential programming of sperm and eggs in gonads is a fundamental topic in reproductive biology. Although the sexual fate of germ cells is believed to be determined by signaling factors from sexually differentiated somatic cells in fetal gonads, the molecular mechanism that determines germ cell fate is poorly understood. Herein, we show that mothers against decapentaplegic homolog 4 (SMAD4) in germ cells is required for female-type differentiation. Germ cells in Smad4-deficient ovaries respond to retinoic acid signaling but fail to undergo meiotic prophase I, which coincides with the weaker expression of genes required for follicular formation, indicating that SMAD4 signaling is essential for oocyte differentiation and meiotic progression. Intriguingly, germline-specific deletion of Smad4 in Stra8-null female germ cells resulted in the up-regulation of genes required for male gonocyte differentiation, including Nanos2 and PLZF, suggesting the initiation of male-type differentiation in ovaries. Moreover, our transcriptome analyses of mutant ovaries revealed that the sex change phenotype is achieved without global gene expression changes in somatic cells. Our results demonstrate that SMAD4 and STRA8 are essential factors that regulate the female fate of germ cells. PMID:27606421

  9. Effects of follicle-stimulating hormone and 17beta-estradiol on proliferation of chicken embryonic ovarian germ cells in culture.

    Science.gov (United States)

    Xie, Meina; Zhang, Caiqiao; Zeng, Weidong; Mi, Yuling

    2004-12-01

    The effects of follicle-stimulating hormone (FSH) and 17beta-estradiol (E2) on chicken ovarian germ cell proliferation were evaluated through a germ-somatic cell coculture model. Ovarian cells from the left ovaries of 18-day-old chicken embryos were cultured in serum-free McCoy's 5A medium at 39 degrees C and challenged with FSH (0.25-1.0 IU/mL) or E2 (10(-8)-10(-5) M) alone and in combination for 48 h. The number of germ cells was counted, and the proliferating cells were immunolocalized by a specific antibody against proliferating cell nuclear antigen (PCNA). The labeling index (LI) was determined for germ cells. Results revealed that germ cells could survive and kept proliferating under support of somatic cells. Germ cells were localized by expression of a specific antibody for stem cell factor receptor c-kit. Both FSH (0.25-1.0 IU/mL) and E2 (10(-7)-10(-5) M) alone induced a marked increase in germ cell number (Pchickens near hatching. PMID:15596398

  10. Impact of Bep or Carboplatin Chemotherapy on Testicular Function and Sperm Nucleus of Subjects with Testicular Germ Cell Tumor.

    Science.gov (United States)

    Ghezzi, Marco; Berretta, Massimiliano; Bottacin, Alberto; Palego, Pierfrancesco; Sartini, Barbara; Cosci, Ilaria; Finos, Livio; Selice, Riccardo; Foresta, Carlo; Garolla, Andrea

    2016-01-01

    Young males have testicular germ cells tumors (TGCT) as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO), the treatment of TGCT may include surveillance, radiotherapy, or chemotherapy (CT), basing on tumor histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis, and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide, and cisplatin (BEP), after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group), 54 with carboplatin (CARB group), and 58 were just surveilled (S-group). All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0) and after 12 (T1) and 24 months (T2) from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones, and testicular volume at baseline were not different between groups. At T1, we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S-group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S-group and Carb group. These alterations were persistent after 2 years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after 1 and 2 years from the end of treatment. Despite

  11. IMPACT OF BEP OR CARBOPLATIN CHEMOTHERAPY ON TESTICULAR FUNCTION AND SPERM NUCLEUS OF SUBJECTS WITH TESTICULAR GERM CELL TUMOR

    Directory of Open Access Journals (Sweden)

    Marco eGhezzi

    2016-05-01

    Full Text Available Young males have testicular germ cells tumours (TGCT as the most common malignancy and its incidence is increasing in several countries. Besides unilateral orchiectomy (UO, the treatment of TGCT may include surveillance, radiotherapy or chemotherapy (CT, basing on tumour histology and stage of disease. It is well known that both radio and CT may have negative effects on testicular function, affecting spermatogenesis and sex hormones. Many reports investigated these aspects in patients treated with bleomycin, etoposide and cisplatin (BEP, after UO. In contrast no data are available on the side effects of carboplatin treatment in these patients. We included in this study 212 consecutive subjects who undergone to sperm banking at our Andrology and Human Reproduction Unit after UO for TGCT. Hundred subjects were further treated with one or more BEP cycles (BEP-group, 54 with carboplatin (Carb group and 58 were just surveilled (S-group. All patients were evaluated for seminal parameters, sperm aneuploidy, sperm DNA, sex hormones, volume of the residual testis at baseline (T0 and after 12 (T1 and 24 months (T2 from UO or end of CT. Seminal parameters, sperm aneuploidies, DNA status, gonadic hormones and testicular volume at baseline were not different between groups. At T1 we observed a significant reduction of sperm concentration and sperm count in the BEP group versus baseline and versus both Carb and S- group. A significant increase of sperm aneuploidies was present at T1 in the BEP group. Similarly, the same group at 1 had altered sperm DNA integrity and fragmentation compared with baseline, S group and Carb group. These alterations were persistent after two years from the end of BEP treatment. Despite a slight improvement at T2, the BEP group had still higher percentages of sperm aneuploidies than other groups. No impairment of sperm aneuploidies and DNA status were observed in the Carb group both after one and two years from the end of treatment

  12. Function of RNA-binding Protein Lin28 in Germ Cell Development and Sex Maturation%RNA结合蛋白Lin28在生殖细胞发育和性成熟过程中的作用

    Institute of Scientific and Technical Information of China (English)

    马薇

    2013-01-01

    As a critical heterochronic gene family protein, RNA-binding protein Lin28 and its homologue Lin-28B play an important role in primordial germ cells (PGCs) development, germ cell tumors (GCTs) malignancy and sex maturation. Lin28 binds to the terminal loops of let-7 miRNA precursors, leading to inhibition of let-7 miRNA processing and the induction of uridylation and precursor degradation. Lin28 also selectively binds to the target mRNAs and stimulates their translation. Lin28 is essencial for proper PGCs development and has temporal and spatial expression pattern during PGC development in mouse embryo. Lin28 can both positively and negatively regulate the pool of germ cell numbers. Aberrant expression of LIN28 may be an early lesion in germ cell tumorigenesis. Lin28 regulates the differentiation status of seminorma, embryonal carcinoma likely upsteam of Oct3/4 and Nanog, and is likely to play a related role in normal human germ cell development. In addition, Lin28B gene is associated with earlier breast development in girls, earlier voice breaking and more advanced pubic hair development in boys and faster tempo of height growth in both of them. This review summarizes Lin28-medicated regulation and possible mechanisms on germ cell development and sex maturation.%作为一个关键的异时性基因(heterochronic gene)家族成员蛋白,Lin28及其同源分子Lin28B在原始生殖细胞(PGCs)发生、生殖细胞肿瘤(GCTs)恶化和性发育成熟过程中发挥着重要的调控作用.Lin28不但可与let-7 miRNA家族的前体终末环相结合,从而阻断let-7miRNA的成熟过程,而且可诱导let-7前体尿苷化和降解.同时,Lin28也可选择性地结合mRNA靶基因,从而直接刺激该基因的翻译过程.Lin28对于PGCs的发育分化至关重要,其表达在小鼠PGCs发育过程中具有时空限制性,还可通过正、负双向途径调节PGC池内生殖细胞数.LIN28的异常表达可能是恶性GCTs发生的早期信号.Lin28还可能是Oct3

  13. Obtaining chicken primordial germ cells used for gene transfer: in vitro and in vivo results.

    Science.gov (United States)

    Chojnacka-Puchta, Luiza; Sawicka, Dorota; Lakota, Paweł; Plucienniczak, Grazyna; Bednarczyk, Marek; Plucienniczak, Andrzej

    2015-11-01

    Recently, several attempts have been made to create a generation of transgenic chickens via chimeric intermediates produced by primordial germ cells (PGCs) transfer. This study aimed to compare the influences of different chicken PGCs isolated from circulating blood (bPGCs) or gonads (gPGCs), purification (ACK, Percoll or trypsin) and transfection methods (electroporation or lipofection) on the expression of transgenes in vitro and the migration of modified donor cells to the recipient gonads. The highest average frequency of pEGFP-N1 plasmid-transfected bPGCs (75.8%) was achieved with Percoll density gradient centrifugation and electroporation. After ammonium chloride-potassium (ACK) treatment and lipofection, in vitro transgene expression was only detected in 35.2% of bPGCs. Chimeric chickens were produced from these purified, transfected and cultured cells, and the transgene was detected in the gonads of 44 and 42% of the recipient embryos that had been injected with bPGCs and gPGCs, respectively. These data confirmed that the combination of PGC purification via Percoll centrifugation and electroporation was an effective method for producing transgenic chickens. Subsequently, we used this method with expression vectors for gene hIFNα 2a/hepatitis B virus surface antigen (HBsAg) under the control of the ovalbumin promoter to generate G0 transgenic chickens. Consequently, we observed that 4.9% of the hens and 3.5% of the roosters carried the hIFNα 2a gene, whereas 16.7% of the hens and 2.4% of the roosters carried the HBsAg gene, thus undisputedly confirming the exceptional effectiveness of the applied methods. PMID:25737138

  14. Migratory and adhesive properties of Xenopus laevis primordial germ cells in vitro

    Directory of Open Access Journals (Sweden)

    Aliaksandr Dzementsei

    2013-11-01

    The directional migration of primordial germ cells (PGCs to the site of gonad formation is an advantageous model system to study cell motility. The embryonic development of PGCs has been investigated in different animal species, including mice, zebrafish, Xenopus and Drosophila. In this study we focus on the physical properties of Xenopus laevis PGCs during their transition from the passive to the active migratory state. Pre-migratory PGCs from Xenopus laevis embryos at developmental stages 17–19 to be compared with migratory PGCs from stages 28–30 were isolated and characterized in respect to motility and adhesive properties. Using single-cell force spectroscopy, we observed a decline in adhesiveness of PGCs upon reaching the migratory state, as defined by decreased attachment to extracellular matrix components like fibronectin, and a reduced adhesion to somatic endodermal cells. Data obtained from qPCR analysis with isolated PGCs reveal that down-regulation of E-cadherin might contribute to this weakening of cell-cell adhesion. Interestingly, however, using an in vitro migration assay, we found that movement of X. laevis PGCs can also occur independently of specific interactions with their neighboring cells. The reduction of cellular adhesion during PGC development is accompanied by enhanced cellular motility, as reflected in increased formation of bleb-like protrusions and inferred from electric cell-substrate impedance sensing (ECIS as well as time-lapse image analysis. Temporal alterations in cell shape, including contraction and expansion of the cellular body, reveal a higher degree of cellular dynamics for the migratory PGCs in vitro.

  15. Long-Term Outcomes of Sacrococcygeal Germ Cell Tumors in Infancy and Childhood

    Directory of Open Access Journals (Sweden)

    Rangsan Niramis

    2015-01-01

    Full Text Available Purpose. The aim of this study was to evaluate long-term outcomes of sacrococcygeal germ cell tumors (SC-GCTs over a 15-year period. Materials and Methods. A retrospective review was conducted of all pediatric patients treated for SC-GCTs at our hospital from 1998 to 2012. Results. Fifty-seven patients were treated for SC-GCTs with the most common in Altman’s classification type I. Age at surgery ranged from one day to 5.6 years. Tumor resection and coccygectomy were primarily performed in about 84% of the cases. Pathology revealed mature, immature, malignant sacrococcygeal teratomas (SCTs, and endodermal sinus tumors (ESTs in 41 (72%, 4 (77%, 6 (10.5%, and 6 (10.5%, respectively. Recurrence of discase occurred in 3 of 41 patients with mature teratomas (7.3%; 2 recurrences with mature teratomas and one recurrence with EST. Five of 6 malignant SCTs and 3 of 6 ESTs responded well to the treatment. Alpha-fetoprotein (AFP level was elevated in both malignant teratomas and ESTs. No immediate patient death was noted in any of the 57 cases, but 4 patients with malignant tumors and distant metastasis succumbed at home within 2 years of the initial treatment. Conclusion. Benign SCTs have a significant recurrence rate of approximately 7%. Close follow-up with serial AFP level monitoring should be done for 5 years after initial tumor resection and coccygectomy. The survival rate for malignant SC-GCTs with distant metastasis was unfavorable in the present study.

  16. Obtaining chicken primordial germ cells used for gene transfer: in vitro and in vivo results.

    Science.gov (United States)

    Chojnacka-Puchta, Luiza; Sawicka, Dorota; Lakota, Paweł; Plucienniczak, Grazyna; Bednarczyk, Marek; Plucienniczak, Andrzej

    2015-11-01

    Recently, several attempts have been made to create a generation of transgenic chickens via chimeric intermediates produced by primordial germ cells (PGCs) transfer. This study aimed to compare the influences of different chicken PGCs isolated from circulating blood (bPGCs) or gonads (gPGCs), purification (ACK, Percoll or trypsin) and transfection methods (electroporation or lipofection) on the expression of transgenes in vitro and the migration of modified donor cells to the recipient gonads. The highest average frequency of pEGFP-N1 plasmid-transfected bPGCs (75.8%) was achieved with Percoll density gradient centrifugation and electroporation. After ammonium chloride-potassium (ACK) treatment and lipofection, in vitro transgene expression was only detected in 35.2% of bPGCs. Chimeric chickens were produced from these purified, transfected and cultured cells, and the transgene was detected in the gonads of 44 and 42% of the recipient embryos that had been injected with bPGCs and gPGCs, respectively. These data confirmed that the combination of PGC purification via Percoll centrifugation and electroporation was an effective method for producing transgenic chickens. Subsequently, we used this method with expression vectors for gene hIFNα 2a/hepatitis B virus surface antigen (HBsAg) under the control of the ovalbumin promoter to generate G0 transgenic chickens. Consequently, we observed that 4.9% of the hens and 3.5% of the roosters carried the hIFNα 2a gene, whereas 16.7% of the hens and 2.4% of the roosters carried the HBsAg gene, thus undisputedly confirming the exceptional effectiveness of the applied methods.

  17. Formation of germline chimera Gaok chicken used circulation primordial germ cells (circulation PGCs fresh and thawed

    Directory of Open Access Journals (Sweden)

    Kostaman T

    2014-03-01

    Full Text Available Formation of germline chimeras by transfer of chicken primordial germ cells (PGCs is one of the effective techniques for preservation and regeneration of genetic resources in chickens. This study attempted to form germline chimeras of Gaok chicken buy purifying circulated PGCs of donor embryo before it is transferred to the recipient (White Leghorn chickens=WL and studied the ability of recipient embryo on survival in incubators, and hatchability. This study used 200 fertile eggs of Gaok and 90 fertile WL breed all of the eggs was incubated at 380C and 60% humidity in a portable incubator. PGCs-circulation of the blood collected Gaok embryos at stage 14-16 were taken from the dorsal aorta, and then purified by centrifugation method using nycodenz. PGCs-circulation results further purification frozen in liquid nitrogen before being transferred to the recipient embryo. The results showed that for the development of embryos transferred to the fresh circulation of PGCs-circulation as many as 25 cells can survive up to day 14, while one of the transferred of 50 and 100 cells into recipient embryos was hatched (10%. On the contrari recipient embryos that are transferred to the frozen PGCs-circulation the embryos development was shorter, and only survived until day 10th (treatment 25 cells, day 14th (treatment of 50 cells and day 17th (treatment of 100 cells. It is concluded that the amount of PGCs-circulation embryos transferred to the recipient is one factor that influence the success of the development germline chimeras.

  18. Complete staining of human spermatozoa and immature germ cells combined with phase contrast microscopy

    DEFF Research Database (Denmark)

    Michael, A Y; Drejer, J O; Bagger, P V;

    1987-01-01

    A method combining Janus green B and Thymol blue stains the anterior part of the head, the nuclear membrane, middle piece, and tail of spermatozoa light green and the nucleus deep purple. The method provides excellent stained preparations for the evaluation of sperm morphology by phase contrast...... microscopy. It produces significantly less abnormal spermatozoa compared with the Papanicolaou stain....

  19. Research Progress of Embryonic Stem Cells Differentiating into Germ Cell%胚胎干细胞向生殖细胞分化的研究进展

    Institute of Scientific and Technical Information of China (English)

    饶家辉; 周虚

    2013-01-01

    The germ cells come from the primordial germ cells(PGCs) , in vivo differentiation mechanism of which has been basically understood. With the development of germ cell studies, in vitro induction of germ cells has become the reality. Embryonic stem cells(ESCs) can be induced to differentiate into epiblast-like cells, then into primordial germ-like or primordial germ cells. When transferred into fetal gland they have the abilities to undergo meiosis and create sperm; when transferred together with ovum into gonad of newly born mouse lacking of seminiferous tubule, they can engender healthy offspring. Therefore, induction of germ cells in vitro further elucidates the mechanism of the ESCs differentiating into germ cells, and lays the foundation for more effective utilization of stem cells to benefit mankind.%生殖细胞来源于原始生殖细胞,其在体内的分化机制已基本清楚.随着生殖细胞研究的不断深入,通过体外诱导途径获得生殖细胞已成为现实.将胚胎干细胞体外分化为上胚层样细胞,进而分化为原始生殖样或原始生殖细胞.将它们迁移入胎儿生殖腺,具有减数分裂及产生精子能力,与卵子结合移入缺生精管的生殖腺的新生鼠可以产生健康后代.为此,体外诱导生殖细胞的成功,进一步阐明了胚胎干细胞向生殖细胞分化的机制,为更有效利用干细胞造福人类奠定了基础.

  20. Effect of microgravity on primordial germ cells (PGCs) in silk chicken offspring ( Gallus gallus domesticus)

    Science.gov (United States)

    Zhou, Zhenming; Li, Zandong

    2011-08-01

    Primordial germ cells (PGCs), precursors of germline cells, display a variety of antigens during their migration to target gonads. Here, we used silk chicken offspring ( Gallus gallus domesticus) embryos subjected to space microgravity to investigate the influence of microgravity on PGCs. The ShenZhou-3 unmanned spaceship carried nine fertilized silk chicken eggs, named the flight group, returned to Earth after 7 days space flight. And the control group has the same clan with the flight group. PGCs from flight and control group silk chicken offspring embryos were examined during migration by using two antibodies (2C9 and anti-SSEA-1), in combination with the horseradish peroxidase detection system, and using periodic acid-Schiff's solution (PAS) reaction. After incubation for about 30 h, SSEA-1 and 2C9 positive cells were detected in the germinal crescent of flight and control group silk chicken offspring embryos. After incubation of eggs for 2-2.5 days, SSEA-1 and 2C9 positive cells were detected in embryonic blood vessels of flight and control group silk chicken offspring embryos. After incubation of eggs for 5.5 days, PGCs in the dorsal mesentery and gonad could also be identified in flight and control group silk chicken offspring embryos by using SSEA-1 and 2C9 antibodies. Based on location and PAS staining, these cells were identified as PGCs. Meanwhile, at the stage of PGCs migration and then becoming established in the germinal ridges, no difference in SSEA-1 or 2C9 staining was detected between female and male PGCs in flight and control group silk chicken offspring embryos. Although there were differences in the profiles of PGC concentration between male and female embryos during the special circulating stage, changing profile of PGCs concentration was similar in same sex between flight and control group offspring embryos. We concluded that there is little effect on PGCs in offspring embryos of microgravity-treated chicken and that PGC development appears