Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression

Ianina C. Ferder and Ning Wang _

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Oncotarget. 2015; 6:15891-15901. https://doi.org/10.18632/oncotarget.4045

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Abstract

Ianina C. Ferder1,2 and Ning Wang1,2

1 Vincent Center for Reproductive Biology, MGH Vincent Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts, USA

2 Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to:

Ning Wang, email:

Keywords: spermatogonial stem cell, aging, Plzf, mTORC1, differentiation

Received: March 21, 2015 Accepted: April 23, 2015 Published: May 08, 2015

Abstract

Like stem cells in other tissues, spermatogonia, including spermatogonial stem cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays an essential role in spermatogonia maintenance by preventing their differentiation. To evaluate whether there is an age-related change in Plzf expression, we found that aged mouse testes exhibited a robust “Plzf overexpression” phenotype, in that they showed not only a higher frequency of Plzf-expressing cells but also an increased level of Plzf expression in these cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly appeared in the differentiating spermatogonia compartment, which is usually low or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for meiosis initiation. These data, together with our observation of a lack of meiosis-initiating spermatocytes associated with high Plzf-expressing spermatogonia in the aged testes, particularly in the degenerative seminiferous tubules, suggest that age-related increase in Plzf expression represents a novel molecular signature of spermatogonia aging by functionally arresting their differentiation.


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