On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer
Human primordial germ cells (PGCs) have been described in the yolk sac wall around the beginning of the third week. From week 4 to 5, they migrate under control of SCF/c-KIT signaling pathway to the genital ridge, where they become gonocytes. PGCs and gonocytes express classic pluripotency markers,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fendo.2019.00343/full |
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| author | Tiziano Baroni Iva Arato Francesca Mancuso Riccardo Calafiore Riccardo Calafiore Giovanni Luca Giovanni Luca |
| author_facet | Tiziano Baroni Iva Arato Francesca Mancuso Riccardo Calafiore Riccardo Calafiore Giovanni Luca Giovanni Luca |
| author_sort | Tiziano Baroni |
| collection | DOAJ |
| description | Human primordial germ cells (PGCs) have been described in the yolk sac wall around the beginning of the third week. From week 4 to 5, they migrate under control of SCF/c-KIT signaling pathway to the genital ridge, where they become gonocytes. PGCs and gonocytes express classic pluripotency markers, such as KIT, NANOG, and OCT3/4 that, during spermatogonia differentiation, are gradually suppressed, and substituted by the expression of some germ cell specific genes, such as VASA, SOX17, and TSPY. These genes, during normal development of germ cells, are tightly regulated by epigenetic modification, in terms of microRNA expression and DNA methylation. In adolescents and young adults, testicular germ cell tumors (TGCT) have a common precursor, the germ cell neoplasia in situ (GCNIS); the hypothesis of their origin from PGCs or gonocytes, whose maturation is altered, is widely accepted. The origin of TGCT, probably starting at early stages of embryogenesis, seems to be a part of the Testicular Dysgenesis Syndrome (TDS) where some early PGC/gonocytes, for still unclear reasons, are blocked in their differentiation, retaining their early marker profile. In this paper, current knowledge on the combination of epidemiological and genomic factors, involved in the development of testicular germ cell tumors, is reviewed. |
| first_indexed | 2024-12-20T02:39:47Z |
| format | Article |
| id | doaj.art-cdce3a51f8f84f038f64de27451b266c |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-20T02:39:47Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-cdce3a51f8f84f038f64de27451b266c2022-12-21T19:56:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922019-06-011010.3389/fendo.2019.00343450856On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular CancerTiziano Baroni0Iva Arato1Francesca Mancuso2Riccardo Calafiore3Riccardo Calafiore4Giovanni Luca5Giovanni Luca6Department of Experimental Medicine, University of Perugia, Perugia, ItalyDepartment of Experimental Medicine, University of Perugia, Perugia, ItalyDepartment of Experimental Medicine, University of Perugia, Perugia, ItalyDepartment of Medicine, University of Perugia, Perugia, ItalyDivision of Medical Andrology and Endocrinology of Reproduction, University of Perugia and Saint Mary Hospital, Terni, ItalyDepartment of Experimental Medicine, University of Perugia, Perugia, ItalyDivision of Medical Andrology and Endocrinology of Reproduction, University of Perugia and Saint Mary Hospital, Terni, ItalyHuman primordial germ cells (PGCs) have been described in the yolk sac wall around the beginning of the third week. From week 4 to 5, they migrate under control of SCF/c-KIT signaling pathway to the genital ridge, where they become gonocytes. PGCs and gonocytes express classic pluripotency markers, such as KIT, NANOG, and OCT3/4 that, during spermatogonia differentiation, are gradually suppressed, and substituted by the expression of some germ cell specific genes, such as VASA, SOX17, and TSPY. These genes, during normal development of germ cells, are tightly regulated by epigenetic modification, in terms of microRNA expression and DNA methylation. In adolescents and young adults, testicular germ cell tumors (TGCT) have a common precursor, the germ cell neoplasia in situ (GCNIS); the hypothesis of their origin from PGCs or gonocytes, whose maturation is altered, is widely accepted. The origin of TGCT, probably starting at early stages of embryogenesis, seems to be a part of the Testicular Dysgenesis Syndrome (TDS) where some early PGC/gonocytes, for still unclear reasons, are blocked in their differentiation, retaining their early marker profile. In this paper, current knowledge on the combination of epidemiological and genomic factors, involved in the development of testicular germ cell tumors, is reviewed.https://www.frontiersin.org/article/10.3389/fendo.2019.00343/fullgerm cell neoplasia in situ (GCNIS)primordial germ cell (PGC)testicular germ cell tumors (TGCTs)testicular dysgenesis syndrome (TDS)Sertoli cellsLeydig cells |
| spellingShingle | Tiziano Baroni Iva Arato Francesca Mancuso Riccardo Calafiore Riccardo Calafiore Giovanni Luca Giovanni Luca On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer Frontiers in Endocrinology germ cell neoplasia in situ (GCNIS) primordial germ cell (PGC) testicular germ cell tumors (TGCTs) testicular dysgenesis syndrome (TDS) Sertoli cells Leydig cells |
| title | On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer |
| title_full | On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer |
| title_fullStr | On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer |
| title_full_unstemmed | On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer |
| title_short | On the Origin of Testicular Germ Cell Tumors: From Gonocytes to Testicular Cancer |
| title_sort | on the origin of testicular germ cell tumors from gonocytes to testicular cancer |
| topic | germ cell neoplasia in situ (GCNIS) primordial germ cell (PGC) testicular germ cell tumors (TGCTs) testicular dysgenesis syndrome (TDS) Sertoli cells Leydig cells |
| url | https://www.frontiersin.org/article/10.3389/fendo.2019.00343/full |
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