ETV5 Is Required for Continuous Spermatogenesis in Adult Mice and May Mediate Blood–Testes Barrier Function and Testicular Immune Privilege

Morrow, Carla M.K.; Hostetler, Chris E.; Griswold, M. D.; Hofmann, Marie‐Claude; Murphy, Kenneth M.; Cooke, Paul S.; Hess, Rex A.

doi:10.1196/annals.1411.005

Cited by 51 publications

(37 citation statements)

References 19 publications

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“…Mice with a targeted Etv5 deletion undergo the first wave of spermatogenesis, but they subsequently show progressive germ cell depletion and a Sertoli cell-only syndrome (Chen et al, 2005). Whether the defect was caused by Sertoli or germ cell dysfunction was unclear in the initial study, but germ cell transplantation experiments later showed that Etv5 is important in both germ cells and Sertoli cells and that Etv5-deficient SSCs have a limited ability to colonize seminiferous tubules of wild-type mice (Morrow et al, 2007;Tyage et al, 2009). By contrast, Bcl6b is not expressed in Sertoli cells, and the involvement of this gene in SSCs was discovered by microarray analyses of cultured spermatogonia stimulated with GDNF.…”

Section: Discussionmentioning

confidence: 99%

FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation ofEtv5andBcl6bthrough MAP2K1 activation

et al. 2012

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SUMMARYFibroblast growth factor 2 (FGF2) and glial cell line-derived neurotrophic factor (GDNF) are required to recapitulate spermatogonial stem cell (SSC) self-renewal in vitro. Although studies have revealed the role of the GDNF signaling pathway in SSCs, little is known about how FGF2 is involved. In the present study, we assessed the role of the FGF2 signaling pathway using a mouse germline stem (GS) cell culture system that allows in vitro expansion of SSCs. Adding GDNF or FGF2 induced phosphorylation of MAPK1/3, and adding the MAP2K1 inhibitor PD0325091 reduced GS cell proliferation and MAPK1/3 phosphorylation. Moreover, GS cells transfected with an activated form of Map2k1 not only upregulated Etv5 and Bcl6b gene expression, but also proliferated in an FGF2-independent manner, suggesting that they act downstream of MAP2K1 signaling to drive SSC self-renewal. Although GS cells transfected with Map2k1, Etv5 or Bcl6b showed normal spermatogonial markers, transplanting GS cells expressing Bcl6b into infertile mouse testes resulted in the formation of a germ cell tumor, suggesting that excessive self-renewal signals causes tumorigenic conversion. These results show that FGF2 depends on MAP2K1 signaling to drive SSC self-renewal via upregulation of the Etv5 and Bcl6b genes.

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Section: Discussionmentioning

confidence: 99%

FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation ofEtv5andBcl6bthrough MAP2K1 activation

et al. 2012

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“…ERM may be needed for maintenance of the blood-testis barrier and testicular immune privilege (Morrow et al, 2007). During postnatal development, spermatogonial loss in Erm 2/2 mice occurs between 4 and 8 days of age and is dramatic by 28 days.…”

Section: Spermatogonia and Their Dependencementioning

confidence: 99%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: Background to spermatogenesis, spermatogonia, and spermatocytes

Hermo

Pelletier

Cyr

et al. 2009

Microscopy Res & Technique

400

232

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As germ cells divide and differentiate from spermatogonia to spermatozoa, they share a number of structural and functional features that are common to all generations of germ cells and these features are discussed herein. Germ cells are linked to one another by large intercellular bridges which serve to move molecules and even large organelles from the cytoplasm of one cell to another. Mitochondria take on different shapes and features and topographical arrangements to accommodate their specific needs during spermatogenesis. The nuclear envelope and pore complex also undergo extensive modifications concomitant with the development of germ cell generations. Apoptosis is an event that is normally triggered by germ cells and involves many proteins. It occurs to limit the germ cell pool and acts as a quality control mechanism. The ubiquitin pathway comprises enzymes that ubiquitinate as well as deubiquitinate target proteins and this pathway is present and functional in germ cells. Germ cells express many proteins involved in water balance and pH control as well as voltage-gated ion channel movement. In the nucleus, proteins undergo epigenetic modifications which include methylation, acetylation, and phosphorylation, with each of these modifications signaling changes in chromatin structure. Germ cells contain specialized transcription complexes that coordinate the differentiation program of spermatogenesis, and there are many male germ cell-specific differences in the components of this machinery. All of the above features of germ cells will be discussed along with the specific proteins/genes and abnormalities to fertility related to each topic.

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“…Studies using reciprocal transplantation of neonatal germ cells from wild-type and Etv5 À/À testes into W/W v recipient testes showed that ETV5 expression in neonatal germ cells is required for the initial establishment of the SSC pool and for homeostasis of SSC self-renewal and differentiation (19). ETV5 expression in Sertoli cells is critical for maintaining normal spermatogenesis (19).…”

mentioning

confidence: 99%

Genetic variants in the ETV5 gene in fertile and infertile men with nonobstructive azoospermia associated with Sertoli cell–only syndrome

O'Bryan

Grealy

Stahl

et al. 2012

Fertility and Sterility

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ETV5 Is Required for Continuous Spermatogenesis in Adult Mice and May Mediate Blood–Testes Barrier Function and Testicular Immune Privilege

Cited by 51 publications

References 19 publications

FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation ofEtv5andBcl6bthrough MAP2K1 activation

FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation ofEtv5andBcl6bthrough MAP2K1 activation

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 1: Background to spermatogenesis, spermatogonia, and spermatocytes

Genetic variants in the ETV5 gene in fertile and infertile men with nonobstructive azoospermia associated with Sertoli cell–only syndrome

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