ROS-Generating Oxidase Nox3 Regulates the Self-Renewal of Mouse Spermatogonial Stem Cells1

Spermatogonial stem cells (SSCs) represent a unique population of germ cells with self-renewal potential. Although reactive oxygen species (ROS) are considered toxic to germ cells, we recently showed that moderate levels of ROS are required for SSC self-renewal and that Nox1 is involved in ROS gener...

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Bibliographic Details
Published in:Biology of reproduction 2015-06, Vol.92 (6)
Main Authors: Morimoto, Hiroko, Kanatsu-Shinohara, Mito, Shinohara, Takashi
Format: Article
Language:English
Subjects:
spermatogenesis
spermatogonia
spermatogonial stem cells
stem cells
testis
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Summary:Spermatogonial stem cells (SSCs) represent a unique population of germ cells with self-renewal potential. Although reactive oxygen species (ROS) are considered toxic to germ cells, we recently showed that moderate levels of ROS are required for SSC self-renewal and that Nox1 is involved in ROS generation. In this study, we showed that self-renewal factor treatment induces Nox3 to trigger SSC self-renewal. Nox3 was transiently expressed in cultured spermatogonia by FGF2 and GDNF stimulation, whereas Nox1 was expressed predominantly during the stable phase of proliferation. Nox3 inhibition by short hairpin RNA reduced cytokine-induced ROS generation and limited the proliferation of cultured spermatogonia. Although Nox3 overexpression revealed no apparent effect, depletion of Nox3 decreased the number of SSCs in both cultured spermatogonia and freshly isolated testis cells. Our results suggest that self-renewal of SSCs is regulated by sequential activation of different Nox genes, and underscore the complexity of ROS regulation in the self-renewal division of SSCs.
ISSN:0006-3363
1529-7268
DOI:10.1095/biolreprod.114.127647