scholarly journals Germ cell determination and the developmental origin of germ cell tumors

Development ◽  
2021 ◽  
Vol 148 (8) ◽  
Author(s):  
Peter K. Nicholls ◽  
David C. Page

ABSTRACT In each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal development, when do cells of the germline irreversibly commit to producing gametes? Integrating findings from diverse species, we conclude that the final commitment of the germline to gametogenesis – the process of germ cell determination – occurs after primordial germ cells (PGCs) colonize the gonads. Combining this understanding with medical findings, we present a model whereby germ cell tumors arise from cells that failed to undertake germ cell determination, regardless of their having colonized the gonads. We propose that the diversity of cell types present in these tumors reflects the broad developmental potential of migratory PGCs.

2021 ◽  
Vol 22 (11) ◽  
pp. 5982
Author(s):  
Massimo De Felici ◽  
Francesca Gioia Klinger ◽  
Federica Campolo ◽  
Carmela Rita Balistreri ◽  
Marco Barchi ◽  
...  

In the human embryo, the genetic program that orchestrates germ cell specification involves the activation of epigenetic and transcriptional mechanisms that make the germline a unique cell population continuously poised between germness and pluripotency. Germ cell tumors, neoplasias originating from fetal or neonatal germ cells, maintain such dichotomy and can adopt either pluripotent features (embryonal carcinomas) or germness features (seminomas) with a wide range of phenotypes in between these histotypes. Here, we review the basic concepts of cell specification, migration and gonadal colonization of human primordial germ cells (hPGCs) highlighting the analogies of transcriptional/epigenetic programs between these two cell types.


Author(s):  
Deepti Shrivastava ◽  
Anuradha Kakani ◽  
Indradeep Bannerjee

ABSTRACT Germ cell tumors are derived from primordial germ cells of the ovary. Approximately 25 to 30% of all ovarian tumors are of germ cell origin and of these, 95% are benign and only 3 to 4% are malignant. They are seen mostly in women in their second and third decades of life and very rarely in postmenopausal women. There are many reported cases of ovarian tumor in postmenopausal women but a huge dermoid cyst in postmenopausal women causing prolapse uterus is very rare. Here, we are presenting a rare case of large dermoid cyst in a 58-year-old postmenopausal multiparous woman with third degree uterine prolapse. How to cite this article Kakani A, Bannerjee I, Shrivastava D. A Huge Dermoid Cyst in Postmenopausal Women with Third Degree Uterine Prolapse. J South Asian Feder Menopause Soc 2013;1(1):43-44.


2008 ◽  
Vol 52 (4) ◽  
pp. 333-344 ◽  
Author(s):  
Christopher Runyan ◽  
Ying Gu ◽  
Amanda Shoemaker ◽  
Leendert Looijenga ◽  
Christopher Wylie

1934 ◽  
Vol s2-76 (304) ◽  
pp. 573-614
Author(s):  
RAYMOND MILLARD CABLE

The writer's earlier study (Cable, 1931) on the germ-cell cycle in the adult stage of Cryptocotyle lingua is supplemented by an investigation of germinal development in the larval stages occurring in the marine snail, Littorina littorea. The miracidium-mother-sporocyst was not found although very young rediae were abundant in the material studied. The primordial germ-cells of the young redia are observed in an undifferentiated condition in the body-cavity, which is not well defined due to an abundance of connective tissue. After a period of differentiation, including growth, progressive nuclear changes, and condensation of cytoplasm, the germ-cells multiply by equal division, a process which is interpreted as polyembryony. Germinal differentiation exhibits a distinct anterior-posterior gradient. The mature germinal cells give rise directly to cercarial embryos without germ-mass formation and dissociation or any maturation processes. Although germinal lineage may be traced in the redia, it seems to be interrupted in the cercaria, due to delayed segregation of germ-cells. The soma of the redia does not produce germ-cells at any stage. Evidence is afforded by this and other studies that germinal lineage with sudden intercalations of polyembryonic stages (germ-masses) cannot explain the germinal cycle of the trematodes as a group. In an alternative hypothesis, based on the phylogeny of the Digenea, it is suggested that the ancestors of this group became sexually mature in the mollusc and completed the cycle in that host, possibly before the appearance of vertebrates; and that, with the evolution of the trematodes, sexual phenomena have gradually been lost, while accessory stages and new hosts have been included in the life-cycle. Cryptocotyle lingua is assumed to have been modified to an intermediate extent since sexual reproduction, germ-masses, and the maximum number of intercalary stages are lacking in the larval generations.


2001 ◽  
Vol 13 (8) ◽  
pp. 661 ◽  
Author(s):  
Anne McLaren ◽  
Gabriela Durcova-Hills

For many years, attempts to achieve long-term culture of mouse primordial germ cells (PGCs) proved unsuccessful, even when feeder layers were used and individual growth factors were added to the medium. However, when three growth factors were added simultaneously to the medium, some of the cells continued to proliferate indefinitely. Similar to embryonic stem cell lines, these embryonic germ (EG) cell lines were capable of giving rise to embryoid bodies in vitro, and colonizing all cell lineages in chimeras, including the germline. Initially, EG cells were made from PGCs before migration, 8.5 days post coitum (dpc), and after entry into the genital ridge, 11.5 and 12.5 dpc. New EG cell lines from 9.5 dpc (migrating) and 11.5 dpc PGCs, carrying either a LacZ or GFP transgene, are described here. The developmental potential of the new EG cell lines in vitro, in vivoin chimeras, and in tissue aggregates in organ culture was studied. The EG cells were compared with PGCs at the stage from which the EG cells were derived. The two cell types show several similarities, but also some differences in gene expression and cell behaviour, which require further exploration.


Development ◽  
1999 ◽  
Vol 126 (9) ◽  
pp. 1823-1832 ◽  
Author(s):  
Y. Kato ◽  
W.M. Rideout ◽  
K. Hilton ◽  
S.C. Barton ◽  
Y. Tsunoda ◽  
...  

There are distinctive and characteristic genomic modifications in primordial germ cells that distinguish the germ cell lineage from somatic cells. These modifications include, genome-wide demethylation, erasure of allele-specific methylation associated with imprinted genes, and the re-activation of the X chromosome. The allele-specific differential methylation is involved in regulating the monoallelic expression, and thus the gene dosage, of imprinted genes, which underlies functional differences between parental genomes. However, when the imprints are erased in the germ line, the parental genomes acquire an equivalent epigenetic and functional state. Therefore, one of the reasons why primordial germ cells are unique is because this is the only time in mammals when the distinction between parental genomes ceases to exist. To test how the potentially imprint-free primordial germ cell nuclei affect embryonic development, we transplanted them into enucleated oocytes. Here we show that the reconstituted oocyte developed to day 9.5 of gestation, consistently as a small embryo and a characteristic abnormal placenta. The embryo proper also did not progress much further even when the inner cell mass was ‘rescued’ from the abnormal placenta by transfer into a tetraploid host blastocyst. We found that development of the experimental conceptus was affected, at least in part, by a lack of gametic imprints, as judged by DNA methylation and expression analysis of several imprinted genes. The evidence suggests that gametic imprints are essential for normal development, and that they can neither be initiated nor erased in mature oocytes; these properties are unique to the developing germ line.


Epigenomics ◽  
2014 ◽  
Vol 6 (3) ◽  
pp. 253-255 ◽  
Author(s):  
Jesús del Mazo ◽  
Jesús García-López ◽  
Michael Weber

2019 ◽  
Vol 116 (51) ◽  
pp. 25677-25687 ◽  
Author(s):  
Peter K. Nicholls ◽  
Hubert Schorle ◽  
Sahin Naqvi ◽  
Yueh-Chiang Hu ◽  
Yuting Fan ◽  
...  

Mammalian primordial germ cells (PGCs) are induced in the embryonic epiblast, before migrating to the nascent gonads. In fish, frogs, and birds, the germline segregates even earlier, through the action of maternally inherited germ plasm. Across vertebrates, migrating PGCs retain a broad developmental potential, regardless of whether they were induced or maternally segregated. In mammals, this potential is indicated by expression of pluripotency factors, and the ability to generate teratomas and pluripotent cell lines. How the germline loses this developmental potential remains unknown. Our genome-wide analyses of embryonic human and mouse germlines reveal a conserved transcriptional program, initiated in PGCs after gonadal colonization, that differentiates germ cells from their germline precursors and from somatic lineages. Through genetic studies in mice and pigs, we demonstrate that one such gonad-induced factor, the RNA-binding protein DAZL, is necessary in vivo to restrict the developmental potential of the germline; DAZL’s absence prolongs expression of aNanogpluripotency reporter, facilitates derivation of pluripotent cell lines, and causes spontaneous gonadal teratomas. Based on these observations in humans, mice, and pigs, we propose that germ cells are determined after gonadal colonization in mammals. We suggest that germ cell determination was induced late in embryogenesis—after organogenesis has begun—in the common ancestor of all vertebrates, as in modern mammals, where this transition is induced by somatic cells of the gonad. We suggest that failure of this process of germ cell determination likely accounts for the origin of human testis cancer.


2018 ◽  
Vol 25 (5) ◽  
pp. 575-583 ◽  
Author(s):  
Paolo Chieffi

Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Methods: I undertook a search of bibliographic data from peer-reviewed research literature. Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies. Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment.


Author(s):  
Gerson Ejeckam ◽  
Margaret G. Norman ◽  
Leslie P. Ivan

SUMMARY:A case of a primary intracranial embryonal carcinoma, the first with ultrastructural study, is reported. The tumor was associated with precocious puberty in a 6½-year-old female. Characteristic embryoid bodies were present. At the ultrastructural level three cell types were noted: undifferentiated, differentiated, and intermediate types. The undifferentiated showed scanty cytoplasmic organelles and numerous free polysomes, while the differentiated cells contained well-developed mitochondria, Golgi apparatus, rough endoplasmic reticulum, and some contained secretory granules. The intermediate cells possessed dilated and irregularly-shaped mitochondria but still retained large numbers of free polysomes. The authors suggest that intracranial germ cell tumors be named in conformity with germ cell tumors in other sites, and that terms such as “ectopic pinealoma” and “atypical teratoma of the pineal” be used no longer.


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