{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:29:04Z","timestamp":1790504944519,"version":"4.1.0"},"reference-count":93,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2013,2,19]],"date-time":"2013-02-19T00:00:00Z","timestamp":1361232000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Since the beginning of the 20th century there has been a decline in the reproductive vitality of men within the Western world. The declining sperm quantity and quality has been associated with increased overt disorders of sexual development including hypospadias, undescended testes and type II testicular germ cell tumours (TGCTs). The increase in TGCTs cannot be accounted for by genetic changes in the population. Therefore exposure to environmental toxicants appears to be a major contributor to the aetiology of TGCTs and men with a genetic predisposition are particularly vulnerable. In particular, Type II TGCTs have been identified to arise from a precursor lesion Carcinoma\n                    <ns4:italic>in situ<\/ns4:italic>\n                    (CIS), identified as a dysfunctional gonocyte; however, the exact triggers for CIS development are currently unknown. Therefore the transition from gonocytes into spermatogonia is key to those studying TGCTs. Recently we have identified seven miRNA molecules (including members of the miR-290 family and miR-136, 463* and 743a) to be significantly changed over this transition period. These miRNA molecules are predicted to have targets within the CXCR4, PTEN, DHH, RAC and PDGF pathways, all of which have important roles in germ cell migration, proliferation and homing to the spermatogonial stem cell niche. Given the plethora of potential targets affected by each miRNA molecule, subtle changes in miRNA expression could have significant consequences e.g. tumourigenesis. The role of non-traditional oncogenes and tumour suppressors such as miRNA in TGCT is highlighted by the fact that the majority of these tumours express wild type p53, a pivotal tumour suppressor usually inactivated in cancer. While treatment of TGCTs is highly successful, the impact of these treatments on fertility means that identification of exact triggers, earlier diagnosis and alternate treatments are essential. This review examines the genetic factors and possible triggers of type II TGCT to highlight target areas for potential new treatments.\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.2-55.v1","type":"journal-article","created":{"date-parts":[[2013,5,9]],"date-time":"2013-05-09T12:08:38Z","timestamp":1368101318000},"page":"55","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["The rise of testicular germ cell tumours: the search for causes, risk factors and novel therapeutic targets"],"prefix":"10.12688","volume":"2","author":[{"given":"Skye C","family":"McIver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun D","family":"Roman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Nixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L","family":"Loveland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen A","family":"McLaughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2013,2,19]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"222-230","DOI":"10.1016\/j.siny.2012.05.004","article-title":"Fetal and neonatal germ cell tumors.","volume":"17","author":"A Frazier","year":"2012","journal-title":"Semin Fetal Neonatal Med."},{"key":"ref-2","doi-asserted-by":"crossref","first-page":"1267-1280","DOI":"10.5858\/2007-131-1267-AOOTGC","article-title":"An overview of testicular germ cell tumors.","volume":"131","author":"A Bahrami","year":"2007","journal-title":"Arch Pathol Lab Med."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"e234-e251","DOI":"10.1111\/j.1365-2605.2011.01157.x","article-title":"Dissecting the molecular pathways of (testicular) germ cell tumour pathogenesis; from initiation to treatment-resistance.","volume":"34","author":"L Looijenga","year":"2011","journal-title":"Int J Androl."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"111-118","DOI":"10.1016\/j.mce.2008.02.018","article-title":"Origin of pluripotent germ cell tumours: the role of microenvironment during embryonic development.","volume":"288","author":"D Kristensen","year":"2008","journal-title":"Mol Cell Endocrinol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"1043-1049","DOI":"10.1007\/s10552-008-9168-z","article-title":"Trends in testicular germ cell cancer incidence in Australia.","volume":"19","author":"P Baade","year":"2008","journal-title":"Cancer Causes Control."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"198-204","DOI":"10.1111\/j.1365-2605.2007.00776.x","article-title":"Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations.","volume":"30","author":"N Skakkebaek","year":"2007","journal-title":"Int J Androl."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"155-161","DOI":"10.1007\/s10552-007-9081-x","article-title":"Doubling of testicular cancer incidence rate over the last 20 years in southern France.","volume":"19","author":"M Walschaerts","year":"2008","journal-title":"Cancer Causes Control."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"230-240","DOI":"10.1111\/j.1365-2605.2007.00760.x","article-title":"Genetic and environmental risk factors for testicular cancer.","volume":"30","author":"L Richiardi","year":"2007","journal-title":"Int J Androl."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"1136-1138","DOI":"10.4161\/cc.4.9.1992","article-title":"Search for testicular cancer gene hits dead-end.","volume":"4","author":"A Matin","year":"2005","journal-title":"Cell Cycle."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"101-108","DOI":"10.1530\/ERC-11-0340","article-title":"Variants in KITLG predispose to testicular germ cell cancer independently from spermatogenic function.","volume":"19","author":"A Ferlin","year":"2012","journal-title":"Endocr Relat Cancer."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"337-348","DOI":"10.1111\/j.1365-2605.2007.00769.x","article-title":"KIT and RAS signalling pathways in testicular germ cell tumours: new data and a review of the literature.","volume":"30","author":"N Goddard","year":"2007","journal-title":"Int J Androl."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"811-815","DOI":"10.1038\/ng.393","article-title":"Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer.","volume":"41","author":"P Kanetsky","year":"2009","journal-title":"Nat Genet."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"305-313","DOI":"10.1016\/S0002-9440(10)63120-3","article-title":"KIT mutations are common in testicular seminomas.","volume":"164","author":"K Kemmer","year":"2004","journal-title":"Am J Pathol."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"588-594","DOI":"10.1111\/j.1365-2605.2007.00813.x","article-title":"Subfertility among parents of men diagnosed with testicular cancer.","volume":"31","author":"E Aschim","year":"2008","journal-title":"Int J Androl."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"419-427","DOI":"10.1097\/01.mou.0000250282.37366.d2","article-title":"Testicular cancer and male infertility.","volume":"16","author":"D Paduch","year":"2006","journal-title":"Curr Opin Urol."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"5241-5250","DOI":"10.1158\/0008-5472.CAN-08-4554","article-title":"Analysis of gene expression profiles of microdissected cell populations indicates that testicular carcinoma in situ is an arrested gonocyte.","volume":"69","author":"S Sonne","year":"2009","journal-title":"Cancer Res."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"393-409","DOI":"10.1387\/ijdb.082671pw","article-title":"Foetal germ cells: striking the balance between pluripotency and differentiation.","volume":"53","author":"P Western","year":"2009","journal-title":"Int J Dev Biol."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"4688-4696","DOI":"10.1128\/MCB.00272-08","article-title":"Normal germ line establishment in mice carrying a deletion of the Ifitm\/Fragilis gene family cluster.","volume":"28","author":"U Lange","year":"2008","journal-title":"Mol Cell Biol."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"715-721","DOI":"10.1016\/j.ceb.2010.09.005","article-title":"The nuts and bolts of germ-cell migration.","volume":"22","author":"K Tarbashevich","year":"2010","journal-title":"Curr Opin Cell Biol."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"477-488","DOI":"10.1093\/molehr\/gas025","article-title":"The pluripotency factor LIN28 in monkey and human testes: a marker for spermatogonial stem cells?","volume":"18","author":"N Aeckerle","year":"2012","journal-title":"Mol Hum Reprod."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"394-396","DOI":"10.1126\/science.1137545","article-title":"Germ cell specification in mice.","volume":"316","author":"K Hayashi","year":"2007","journal-title":"Science."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"435-437","DOI":"10.1111\/j.1432-0436.2005.00049.x","article-title":"How is the mouse germ-cell lineage established?","volume":"73","author":"A McLaren","year":"2005","journal-title":"Differentiation."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"337-341","DOI":"10.1016\/j.gde.2008.06.003","article-title":"Mouse germ cell development during embryogenesis.","volume":"18","author":"Y Saga","year":"2008","journal-title":"Curr Opin Genet Dev."},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"207-213","DOI":"10.1038\/nature03813","article-title":"Blimp1 is a critical determinant of the germ cell lineage in mice.","volume":"436","author":"Y Ohinata","year":"2005","journal-title":"Nature."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"425863","DOI":"10.4061\/2011\/425863","article-title":"Nuclear reprogramming in mouse primordial germ cells: epigenetic contribution.","volume":"2011","author":"M De Felici","year":"2011","journal-title":"Stem Cells Int."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"753-761","DOI":"10.1007\/s00109-012-0912-1","article-title":"The reciprocal relationship between primordial germ cells and pluripotent stem cells.","volume":"90","author":"M Pirouz","year":"2012","journal-title":"J Mol Med (Berl)."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"705-716","DOI":"10.1095\/biolreprod.106.053686","article-title":"Gene expression dynamics during germline specification in mice identified by quantitative single-cell gene expression profiling.","volume":"75","author":"Y Yabuta","year":"2006","journal-title":"Biol Reprod."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"1078-1083","DOI":"10.1038\/sj.embor.7400279","article-title":"Oct4 is required for primordial germ cell survival.","volume":"5","author":"J Kehler","year":"2004","journal-title":"EMBO Rep."},{"key":"ref-29","doi-asserted-by":"publisher","first-page":"19-28","DOI":"10.1634\/stemcells.2006-0269","article-title":"Dppa2 and Dppa4 are closely linked SAP motif genes restricted to pluripotent cells and the germ line.","volume":"25","author":"J Maldonado-Saldivia","year":"2007","journal-title":"Stem Cells."},{"key":"ref-30","doi-asserted-by":"publisher","first-page":"1230-1234","DOI":"10.1038\/nature06403","article-title":"Nanog safeguards pluripotency and mediates germline development.","volume":"450","author":"I Chambers","year":"2007","journal-title":"Nature."},{"key":"ref-31","doi-asserted-by":"publisher","first-page":"e160-e174","DOI":"10.1111\/j.1365-2605.2011.01148.x","article-title":"Expression and interdependencies of pluripotency factors LIN28, OCT 3\/4, NANOG and SOX2 in human testicular germ cells and tumours of the testis.","volume":"34","author":"A Gillis","year":"2011","journal-title":"Int J Androl."},{"key":"ref-32","doi-asserted-by":"publisher","first-page":"206-220","DOI":"10.1159\/000335031","article-title":"Developmental expression of the pluripotency factor sal-like protein 4 in the monkey, human and mouse testis: restriction to premeiotic germ cells.","volume":"196","author":"K Eildermann","year":"2012","journal-title":"Cells Tissues Organs."},{"key":"ref-33","doi-asserted-by":"publisher","first-page":"284-298","DOI":"10.1016\/j.stem.2012.02.004","article-title":"Functional antagonism between Sall4 and Plzf defines germline progenitors.","volume":"10","author":"R Hobbs","year":"2012","journal-title":"Cell Stem Cell."},{"key":"ref-34","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1095\/biolreprod.111.096792","article-title":"Tracing the conversion process from primordial germ cells to pluripotent stem cells in mice.","volume":"86","author":"G Nagamatsu","year":"2012","journal-title":"Biol Reprod."},{"key":"ref-35","doi-asserted-by":"publisher","first-page":"1-26","DOI":"10.1002\/bdrc.20142","article-title":"Gonocytes, the forgotten cells of the germ cell lineage.","volume":"87","author":"M Culty","year":"2009","journal-title":"Birth Defects Res C Embryo Today."},{"key":"ref-36","doi-asserted-by":"publisher","first-page":"96-113","DOI":"10.1002\/bdrc.20140","article-title":"Recent developments in testicular germ cell tumor research.","volume":"87","author":"G van de Geijn","year":"2009","journal-title":"Birth Defects Res C Embryo Today."},{"key":"ref-37","doi-asserted-by":"publisher","first-page":"37-49","DOI":"10.1038\/nrm2815","article-title":"Mechanisms guiding primordial germ cell migration: strategies from different organisms.","volume":"11","author":"B Richardson","year":"2010","journal-title":"Nat Rev Mol Cell Biol."},{"key":"ref-38","doi-asserted-by":"publisher","first-page":"393-400","DOI":"10.1006\/scdb.1998.0204","article-title":"The origin and migration of primordial germ cells in the mouse.","volume":"9","author":"M Bendel-Stenzel","year":"1998","journal-title":"Semin Cell Dev Biol."},{"key":"ref-39","doi-asserted-by":"publisher","first-page":"572-583","DOI":"10.1016\/j.ydbio.2007.03.031","article-title":"Chemoattractant action and molecular signaling pathways of Kit ligand on mouse primordial germ cells.","volume":"306","author":"D Farini","year":"2007","journal-title":"Dev Biol."},{"key":"ref-40","doi-asserted-by":"publisher","first-page":"1295-1303","DOI":"10.1242\/dev.030619","article-title":"Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration.","volume":"136","author":"Y Gu","year":"2009","journal-title":"Development."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"4279-4286","DOI":"10.1242\/dev.00640","article-title":"The chemokine SDF1\/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival.","volume":"130","author":"K Molyneaux","year":"2003","journal-title":"Development."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"409-413","DOI":"10.1038\/nature11272","article-title":"The H3K27 demethylase Utx regulates somatic and germ cell epigenetic reprogramming.","volume":"488","author":"A Mansour","year":"2012","journal-title":"Nature."},{"key":"ref-43","first-page":"575-580","article-title":"Regulation of primordial germ cell development in the mouse.","volume":"44","author":"M De Felici","year":"2000","journal-title":"Int J Dev Biol."},{"key":"ref-44","doi-asserted-by":"publisher","first-page":"417-420","DOI":"10.1016\/j.biocel.2009.12.005","article-title":"SRY: A transcriptional activator of mammalian testis determination.","volume":"42","author":"R Sekido","year":"2010","journal-title":"Int J Biochem Cell Biol."},{"key":"ref-45","doi-asserted-by":"publisher","first-page":"3921-3930","DOI":"10.1242\/dev.048983","article-title":"Sry: the master switch in mammalian sex determination.","volume":"137","author":"K Kashimada","year":"2010","journal-title":"Development."},{"key":"ref-46","doi-asserted-by":"publisher","first-page":"223-228","DOI":"10.1016\/j.tem.2006.06.009","article-title":"The road to maleness: from testis to Wolffian duct.","volume":"17","author":"I Barsoum","year":"2006","journal-title":"Trends Endocrinol Metab."},{"key":"ref-47","doi-asserted-by":"publisher","first-page":"13-19","DOI":"10.1093\/jb\/mvi098","article-title":"From SRY to SOX9: mammalian testis differentiation.","volume":"138","author":"Y Kanai","year":"2005","journal-title":"J Biochem."},{"key":"ref-48","doi-asserted-by":"publisher","first-page":"205-213","DOI":"10.1093\/molehr\/gap008","article-title":"Germ cell sex determination in mammals.","volume":"15","author":"A Kocer","year":"2009","journal-title":"Mol Hum Reprod."},{"key":"ref-49","doi-asserted-by":"publisher","first-page":"277-280","DOI":"10.1002\/mrd.1088","article-title":"Primordial germ cell-somatic cell partnership: a balancing cell signaling act.","volume":"60","author":"A Kierszenbaum","year":"2001","journal-title":"Mol Reprod Dev."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"3401-3411","DOI":"10.1242\/dev.001107","article-title":"Retinoic acid, meiosis and germ cell fate in mammals.","volume":"134","author":"J Bowles","year":"2007","journal-title":"Development."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"S141-S147","DOI":"10.1111\/j.1440-169X.2008.01009.x","article-title":"Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.","volume":"50","author":"Y Saga","year":"2008","journal-title":"Dev Growth Differ."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"259-282","DOI":"10.1016\/S0076-6879(06)19011-4","article-title":"Spermatogonial stem cells.","volume":"419","author":"J Oatley","year":"2006","journal-title":"Methods Enzymol."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"S51-S60","DOI":"10.1038\/modpathol.3800309","article-title":"Origins and molecular biology of testicular germ cell tumors.","volume":"18","author":"V Reuter","year":"2005","journal-title":"Mod Pathol."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"391-402","DOI":"10.1016\/j.beem.2010.09.011","article-title":"Environmental factors and testicular function.","volume":"25","author":"A Giwercman","year":"2011","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"93-102","DOI":"10.1007\/s12519-009-0020-7","article-title":"Disorders of sex development: update on the genetic background, terminology and risk for the development of germ cell tumors.","volume":"5","author":"M Cools","year":"2009","journal-title":"World J Pediatr."},{"key":"ref-56","doi-asserted-by":"publisher","first-page":"3519-3524","DOI":"10.4161\/cc.7.22.6980","article-title":"Genetic aspects of testicular germ cell tumors.","volume":"7","author":"C Krausz","year":"2008","journal-title":"Cell Cycle."},{"key":"ref-57","doi-asserted-by":"publisher","first-page":"168-180","DOI":"10.1196\/annals.1411.013","article-title":"From gonocytes to testicular cancer: the role of impaired gonadal development.","volume":"1120","author":"E Rajpert-de Meyts","year":"2007","journal-title":"Ann N Y Acad Sci."},{"key":"ref-58","doi-asserted-by":"publisher","first-page":"278-288","DOI":"10.1038\/nrc3021","article-title":"Testicular germ cell tumours: predisposition genes and the male germ cell niche.","volume":"11","author":"D Gilbert","year":"2011","journal-title":"Nat Rev Cancer."},{"key":"ref-59","doi-asserted-by":"publisher","first-page":"1659-1673","DOI":"10.1586\/14737140.8.10.1659","article-title":"Biology of testicular germ cell tumors.","volume":"8","author":"S Hussain","year":"2008","journal-title":"Expert Rev Anticancer Ther."},{"key":"ref-60","doi-asserted-by":"publisher","first-page":"807-810","DOI":"10.1038\/ng.394","article-title":"A genome-wide association study of testicular germ cell tumor.","volume":"41","author":"E Rapley","year":"2009","journal-title":"Nat Genet."},{"key":"ref-61","doi-asserted-by":"publisher","first-page":"342-346","DOI":"10.1055\/s-2008-1073168","article-title":"New insights into germ cell tumor formation.","volume":"40","author":"R Jessberger","year":"2008","journal-title":"Horm Metab Res."},{"key":"ref-62","doi-asserted-by":"publisher","first-page":"128-133","DOI":"10.1034\/j.1600-0463.2003.11101171.x","article-title":"Localisation of susceptibility genes for familial testicular germ cell tumour.","volume":"111","author":"E Rapley","year":"2003","journal-title":"APMIS."},{"key":"ref-63","doi-asserted-by":"publisher","first-page":"5165-5174","DOI":"10.1074\/jbc.M807098200","article-title":"MCAF1\/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase activity.","volume":"284","author":"L Liu","year":"2009","journal-title":"J Biol Chem."},{"key":"ref-64","doi-asserted-by":"publisher","first-page":"1548-1552","DOI":"10.1093\/carcin\/bgs218","article-title":"Replication of genetic susceptibility loci for testicular germ cell cancer in the Croatian population.","volume":"33","author":"D Lessel","year":"2012","journal-title":"Carcinogenesis."},{"key":"ref-65","doi-asserted-by":"publisher","first-page":"295-307","DOI":"10.1093\/humrep\/dep390","article-title":"What has happened to human fertility?","volume":"25","author":"M Joffe","year":"2010","journal-title":"Hum Reprod."},{"key":"ref-66","doi-asserted-by":"publisher","first-page":"532-543","DOI":"10.1038\/ncpuro0606","article-title":"Interpreting the international trends in testicular seminoma and nonseminoma incidence.","volume":"3","author":"F Bray","year":"2006","journal-title":"Nat Clin Pract Urol."},{"key":"ref-67","doi-asserted-by":"publisher","first-page":"90-100","DOI":"10.1530\/ror.0.0040090","article-title":"Pathogenesis of testicular germ cell tumours.","volume":"4","author":"L Looijenga","year":"1999","journal-title":"Rev Reprod."},{"key":"ref-68","doi-asserted-by":"publisher","first-page":"385-392","DOI":"10.1111\/j.1365-2605.2007.00754.x","article-title":"Epigenetic profile of testicular germ cell tumours.","volume":"30","author":"K Okamoto","year":"2007","journal-title":"Int J Androl."},{"key":"ref-69","doi-asserted-by":"publisher","first-page":"146-162","DOI":"10.1002\/path.2522","article-title":"Human testicular (non)seminomatous germ cell tumours: the clinical implications of recent pathobiological insights.","volume":"218","author":"L Looijenga","year":"2009","journal-title":"J Pathol."},{"key":"ref-70","doi-asserted-by":"publisher","first-page":"1577-1586","DOI":"10.1242\/dev.076851","article-title":"Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice.","volume":"139","author":"J Heaney","year":"2012","journal-title":"Development."},{"key":"ref-71","doi-asserted-by":"publisher","first-page":"1893-1898","DOI":"10.1095\/biolreprod63.6.1893","article-title":"Involvement of the D-type cyclins in germ cell proliferation and differentiation in the mouse.","volume":"63","author":"T Beumer","year":"2000","journal-title":"Biol Reprod."},{"key":"ref-72","doi-asserted-by":"publisher","first-page":"94-102","DOI":"10.1002\/path.2436","article-title":"Clinical and biological significance of CXCL12 and CXCR4 expression in adult testes and germ cell tumours of adults and adolescents.","volume":"217","author":"D Gilbert","year":"2009","journal-title":"J Pathol."},{"key":"ref-73","doi-asserted-by":"publisher","first-page":"319-328","DOI":"10.1002\/path.2230","article-title":"High-throughput microRNAome analysis in human germ cell tumours.","volume":"213","author":"A Gillis","year":"2007","journal-title":"J Pathol."},{"key":"ref-74","doi-asserted-by":"publisher","first-page":"304-314","DOI":"10.1111\/j.1365-2605.2007.00765.x","article-title":"Relevance of microRNAs in normal and malignant development, including human testicular germ cell tumours.","volume":"30","author":"L Looijenga","year":"2007","journal-title":"Int J Androl."},{"key":"ref-75","doi-asserted-by":"publisher","first-page":"1169-1181","DOI":"10.1016\/j.cell.2006.02.037","article-title":"A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors.","volume":"124","author":"P Voorhoeve","year":"2006","journal-title":"Cell."},{"key":"ref-76","doi-asserted-by":"publisher","first-page":"44-59","DOI":"10.1093\/humupd\/dmr041","article-title":"miRNA and mammalian male germ cells.","volume":"18","author":"S McIver","year":"2012","journal-title":"Hum Reprod Update."},{"key":"ref-77","doi-asserted-by":"publisher","first-page":"e35553","DOI":"10.1371\/journal.pone.0035553","article-title":"A unique combination of male germ cell miRNAs coordinates gonocyte differentiation.","volume":"7","author":"S McIver","year":"2012","journal-title":"PLoS One."},{"key":"ref-78","doi-asserted-by":"publisher","first-page":"1882-1894","DOI":"10.1038\/sj.onc.1208368","article-title":"Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors.","volume":"24","author":"D Di Vizio","year":"2005","journal-title":"Oncogene."},{"key":"ref-79","doi-asserted-by":"publisher","first-page":"186-195","DOI":"10.1002\/gcc.20843","article-title":"Minimum regions of genomic imbalance in stage I testicular embryonal carcinoma and association of 22q loss with relapse.","volume":"50","author":"D Gilbert","year":"2011","journal-title":"Gene Chromosomes Cancer."},{"key":"ref-80","first-page":"333-340","article-title":"Repression of cyclin D1 as a target for germ cell tumors.","volume":"30","author":"S Freemantle","year":"2007","journal-title":"Int J Oncol."},{"key":"ref-81","doi-asserted-by":"publisher","first-page":"162-165","DOI":"10.1016\/j.ymeth.2007.04.007","article-title":"Isolation of microRNA targets using biotinylated synthetic microRNAs.","volume":"43","author":"U Orom","year":"2007","journal-title":"Methods."},{"key":"ref-82","doi-asserted-by":"publisher","first-page":"6226-6235","DOI":"10.1210\/en.2008-0349","article-title":"Platelet-derived growth factor receptor beta-subtype regulates proliferation and migration of gonocytes.","volume":"149","author":"S Basciani","year":"2008","journal-title":"Endocrinology."},{"key":"ref-83","doi-asserted-by":"publisher","first-page":"463-475","DOI":"10.1016\/j.stem.2011.08.011","article-title":"Rac mediates mouse spermatogonial stem cell homing to germline niches by regulating transmigration through the blood-testis barrier.","volume":"9","author":"S Takashima","year":"2011","journal-title":"Cell Stem Cell."},{"key":"ref-84","doi-asserted-by":"publisher","first-page":"825-836","DOI":"10.1095\/biolreprod.109.081729","article-title":"Interdependence of platelet-derived growth factor and estrogen-signaling pathways in inducing neonatal rat testicular gonocytes proliferation.","volume":"82","author":"R Thuillier","year":"2010","journal-title":"Biol Reprod."},{"key":"ref-85","doi-asserted-by":"crossref","first-page":"1335-1342","DOI":"10.1593\/neo.08694","article-title":"Insulin-like growth factor binding protein 7 mediates glioma cell growth and migration.","volume":"10","author":"W Jiang","year":"2008","journal-title":"Neoplasia."},{"key":"ref-86","doi-asserted-by":"publisher","first-page":"373-384","DOI":"10.1007\/s10549-010-0921-0","article-title":"Insulin like growth factor binding protein-7 reduces growth of human breast cancer cells and xenografted tumors.","volume":"126","author":"Y Amemiya","year":"2011","journal-title":"Breast Cancer Res Treat."},{"key":"ref-87","doi-asserted-by":"publisher","first-page":"6693-6701","DOI":"10.1158\/1078-0432.CCR-10-2774","article-title":"Insulin-like growth factor-binding protein-7 functions as a potential tumor suppressor in hepatocellular carcinoma.","volume":"17","author":"D Chen","year":"2011","journal-title":"Clin Cancer Res."},{"key":"ref-88","doi-asserted-by":"publisher","first-page":"14163-14168","DOI":"10.1073\/pnas.1111241108","article-title":"mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects.","volume":"108","author":"L Medeiros","year":"2011","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-89","doi-asserted-by":"publisher","first-page":"e1002054","DOI":"10.1371\/journal.pgen.1002054","article-title":"A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells.","volume":"7","author":"G Zheng","year":"2011","journal-title":"PLoS Genet."},{"key":"ref-90","doi-asserted-by":"publisher","first-page":"793-803","DOI":"10.1093\/molehr\/gaq053","article-title":"Embryonic stem cell-related miRNAs are involved in differentiation of pluripotent cells originating from the germ line.","volume":"16","author":"A Zovoilis","year":"2010","journal-title":"Mol Hum Reprod."},{"key":"ref-91","doi-asserted-by":"publisher","first-page":"3608-3612","DOI":"10.1016\/j.febslet.2012.08.003","article-title":"MiR-136 promotes apoptosis of glioma cells by targeting AEG-1 and Bcl-2.","volume":"586","author":"Y Yang","year":"2012","journal-title":"FEBS Lett."},{"key":"ref-92","doi-asserted-by":"publisher","first-page":"440-448","DOI":"10.1111\/j.1471-4159.2011.07333.x","article-title":"Up-regulation of the mitochondrial malate dehydrogenase by oxidative stress is mediated by miR-743a.","volume":"118","author":"Q Shi","year":"2011","journal-title":"J Neurochem."},{"key":"ref-93","doi-asserted-by":"publisher","first-page":"303-323","DOI":"10.1093\/humupd\/dmk006","article-title":"Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects.","volume":"12","author":"E Rajpert-De Meyts","year":"2006","journal-title":"Hum Reprod Update."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/2-55\/v1\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-55\/v1\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/2-55\/v1\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,16]],"date-time":"2022-02-16T11:39:37Z","timestamp":1645011577000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/2-55\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,19]]},"references-count":93,"URL":"https:\/\/doi.org\/10.12688\/f1000research.2-55.v1","relation":{"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.805.r790","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.805.r966","asserted-by":"subject"},{"id-type":"doi","id":"10.5256\/f1000research.805.r790","asserted-by":"object"},{"id-type":"doi","id":"10.5256\/f1000research.805.r966","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/2-55\/v1#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.805.r790, Anis Feki, Department of Obstetrics and Gynaecology, Geneva University Hospitals, Geneva, Switzerland, 21 Feb 2013, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/2-55\/v1#referee-response-790","order":0,"name":"referee-response-790","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.805.r966, John Schjenken, Centre for Reproductive Health, University of Adelaide, Adelaide, SA, Australia, 28 May 2013, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/2-55\/v1#referee-response-966","order":1,"name":"referee-response-966","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The authors gratefully acknowledge the financial assistance to EM, SR and BN by the Australian Research Council, National Health and Medical Research Council and the University of Newcastle. SCM is the recipient of an Australian Postgraduate Award PhD scholarship and a University of Newcastle Vice Chancellors Post Graduate Award. This work was supported by the Australian Research Council Centre of Excellence in Biotechnology and Development (CE0348239) to EAM and SDR and a Fellowship from the NHMRC (ID545916 to KL).","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}