Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function.
Spermatogonia stem cell (SSC) self-renewal and differentiation are tightly regulated processes that ensure a continued production of mature sperm throughout male adulthood. In the present study, we investigated the role of glucocorticoid-induced leucine zipper (GILZ) in maintenance of the male germl...
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doaj-33c67fd1907f4df18ade4154f8d139d62020-11-25T00:40:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e5914910.1371/journal.pone.0059149Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function.Devi NgoQiang ChengAnne E O'ConnorKathleen D DeBoerCamden Y LoElaine BeaulieuMia De SeramRobin M HobbsMoira K O'BryanEric F MorandSpermatogonia stem cell (SSC) self-renewal and differentiation are tightly regulated processes that ensure a continued production of mature sperm throughout male adulthood. In the present study, we investigated the role of glucocorticoid-induced leucine zipper (GILZ) in maintenance of the male germline and spermatogenesis. GILZ was detectable in germ cells of wild type mice on the day of birth, suggesting a role for GILZ in prospermatogonia and SSC pool formation. Gilz KO mice were generated and adult males were azoospermic and sterile. During the first wave of spermatogenesis in Gilz KO mice, spermatogenesis arrested part way through pachytene of meiosis I. Subsequent waves resulted in a progressive depletion of germ cells through apoptosis to ultimately produce a Sertoli cell-only phenotype. Further, in contrast to wild type littermates, PLZF(+) cells were detected in the peri-luminal region of Gilz KO mice at day 6 post-natal, suggesting a defect in prospermatogonia migration in the absence of GILZ. At age 30 days, transient accumulation of PLZF(+) cells in a subset of tubules and severely compromised spermatogenesis were observed in Gilz KO mice, consistent with defective SSC differentiation. GILZ deficiency was associated with an increase in FOXO1 transcriptional activity, which leads to activation of a selective set of FOXO1 target genes, including a pro-apoptotic protein, BIM. On the other hand, no evidence of a heightened immune response was observed. Together, these results suggest that GILZ suppresses FOXO1 nuclear translocation, promotes SSC differentiation over self-renewal, and favours germ cell survival through inhibition of BIM-dependent pro-apoptotic signals. These findings provide a mechanism for the effects of GILZ on spermatogenesis and strengthen the case for GILZ being a critical molecule in the regulation of male fertility.http://europepmc.org/articles/PMC3597624?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Devi Ngo Qiang Cheng Anne E O'Connor Kathleen D DeBoer Camden Y Lo Elaine Beaulieu Mia De Seram Robin M Hobbs Moira K O'Bryan Eric F Morand |
spellingShingle |
Devi Ngo Qiang Cheng Anne E O'Connor Kathleen D DeBoer Camden Y Lo Elaine Beaulieu Mia De Seram Robin M Hobbs Moira K O'Bryan Eric F Morand Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. PLoS ONE |
author_facet |
Devi Ngo Qiang Cheng Anne E O'Connor Kathleen D DeBoer Camden Y Lo Elaine Beaulieu Mia De Seram Robin M Hobbs Moira K O'Bryan Eric F Morand |
author_sort |
Devi Ngo |
title |
Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. |
title_short |
Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. |
title_full |
Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. |
title_fullStr |
Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. |
title_full_unstemmed |
Glucocorticoid-induced leucine zipper (GILZ) regulates testicular FOXO1 activity and spermatogonial stem cell (SSC) function. |
title_sort |
glucocorticoid-induced leucine zipper (gilz) regulates testicular foxo1 activity and spermatogonial stem cell (ssc) function. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Spermatogonia stem cell (SSC) self-renewal and differentiation are tightly regulated processes that ensure a continued production of mature sperm throughout male adulthood. In the present study, we investigated the role of glucocorticoid-induced leucine zipper (GILZ) in maintenance of the male germline and spermatogenesis. GILZ was detectable in germ cells of wild type mice on the day of birth, suggesting a role for GILZ in prospermatogonia and SSC pool formation. Gilz KO mice were generated and adult males were azoospermic and sterile. During the first wave of spermatogenesis in Gilz KO mice, spermatogenesis arrested part way through pachytene of meiosis I. Subsequent waves resulted in a progressive depletion of germ cells through apoptosis to ultimately produce a Sertoli cell-only phenotype. Further, in contrast to wild type littermates, PLZF(+) cells were detected in the peri-luminal region of Gilz KO mice at day 6 post-natal, suggesting a defect in prospermatogonia migration in the absence of GILZ. At age 30 days, transient accumulation of PLZF(+) cells in a subset of tubules and severely compromised spermatogenesis were observed in Gilz KO mice, consistent with defective SSC differentiation. GILZ deficiency was associated with an increase in FOXO1 transcriptional activity, which leads to activation of a selective set of FOXO1 target genes, including a pro-apoptotic protein, BIM. On the other hand, no evidence of a heightened immune response was observed. Together, these results suggest that GILZ suppresses FOXO1 nuclear translocation, promotes SSC differentiation over self-renewal, and favours germ cell survival through inhibition of BIM-dependent pro-apoptotic signals. These findings provide a mechanism for the effects of GILZ on spermatogenesis and strengthen the case for GILZ being a critical molecule in the regulation of male fertility. |
url |
http://europepmc.org/articles/PMC3597624?pdf=render |
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