PI3K/PTEN/AKT Signaling Pathways in Germ Cell Development and Their Involvement in Germ Cell Tumors and Ovarian Dysfunctions

Several studies indicate that the PI3K/PTEN/AKT signaling pathways are critical regulators of ovarian function including the formation of the germ cell precursors, termed primordial germ cells, and the follicular pool maintenance. This article reviews the current state of knowledge of the functional role of the PI3K/PTEN/AKT pathways during primordial germ cell development and the dynamics of the ovarian primordial follicle reserve and how dysregulation of these signaling pathways may contribute to the development of some types of germ cell tumors and ovarian dysfunctions.

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From primordial germ cell to primordial follicle: mammalian female germ cell development

genesis ◽

10.1002/dvg.20258 ◽

2006 ◽

Vol 44 (12) ◽

pp. 622-632 ◽

Cited By ~ 198

Author(s):

Melissa E. Pepling

Keyword(s):

Germ Cell ◽

Primordial Germ Cell ◽

Primordial Follicle ◽

Cell Development ◽

Germ Cell Development ◽

Female Germ Cell ◽

Mammalian Female

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SNRPN methylation patterns in germ cell tumors as a reflection of primordial germ cell development

Genes Chromosomes and Cancer ◽

10.1002/gcc.1199 ◽

2001 ◽

Vol 32 (4) ◽

pp. 342-352 ◽

Cited By ~ 40

Author(s):

Kimberly J. Bussey ◽

Helen J. Lawce ◽

Eleanor Himoe ◽

Xiao Ou Shu ◽

Nyla A. Heerema ◽

...

Keyword(s):

Germ Cell ◽

Primordial Germ Cell ◽

Germ Cell Tumors ◽

Cell Development ◽

Germ Cell Development ◽

Methylation Patterns

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IGF2/H19 imprinting analysis of human germ cell tumors (GCTs) using the methylation-sensitive single-nucleotide primer extension method reflects the origin of GCTs in different stages of primordial germ cell development

Genes Chromosomes and Cancer ◽

10.1002/gcc.20237 ◽

2005 ◽

Vol 44 (3) ◽

pp. 256-264 ◽

Cited By ~ 54

Author(s):

Sonja Sievers ◽

Katayoun Alemazkour ◽

Susanne Zahn ◽

Elizabeth J. Perlman ◽

Ad J. M. Gillis ◽

...

Keyword(s):

Germ Cell ◽

Primordial Germ Cell ◽

Germ Cell Tumors ◽

Cell Development ◽

Primer Extension ◽

Single Nucleotide ◽

Extension Method ◽

Germ Cell Development ◽

Single Nucleotide Primer Extension

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Elucidating human male germ cell development by studying germ cell cancer

Reproduction ◽

10.1530/rep-16-0114 ◽

2016 ◽

Vol 152 (4) ◽

pp. R101-R113 ◽

Cited By ~ 6

Author(s):

Daniel Nettersheim ◽

Sina Jostes ◽

Simon Schneider ◽

Hubert Schorle

Keyword(s):

Germ Cell ◽

Regulatory Networks ◽

Primordial Germ Cells ◽

Cell Cancer ◽

Tumor Biology ◽

Germ Cell Tumors ◽

Cell Development ◽

Dna Hypomethylation ◽

Pluripotent Cells ◽

Germ Cell Development

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.

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