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Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome
Sertoli cell-only (SCO) syndrome is a severe form of human male infertility seemingly characterized by the lack all spermatogenic cells. However, tubules of some SCO testes contain small patches of active spermatogenesis and thus spermatogonial stem cells. We hypothesized that these stem cells canno...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508736/ https://www.ncbi.nlm.nih.gov/pubmed/31071133 http://dx.doi.org/10.1371/journal.pone.0216586 |
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author | Paduch, Darius A. Hilz, Stephanie Grimson, Andrew Schlegel, Peter N. Jedlicka, Anne E. Wright, William W. |
author_facet | Paduch, Darius A. Hilz, Stephanie Grimson, Andrew Schlegel, Peter N. Jedlicka, Anne E. Wright, William W. |
author_sort | Paduch, Darius A. |
collection | PubMed |
description | Sertoli cell-only (SCO) syndrome is a severe form of human male infertility seemingly characterized by the lack all spermatogenic cells. However, tubules of some SCO testes contain small patches of active spermatogenesis and thus spermatogonial stem cells. We hypothesized that these stem cells cannot replicate and seed spermatogenesis in barren areas of tubule because as-of-yet unrecognized deficits in Sertoli cell gene expression disable most stem cell niches. Performing the first thorough comparison of the transcriptomes of human testes exhibiting complete spermatogenesis with the transcriptomes of testes with SCO syndrome, we defined transcripts that are both predominantly expressed by Sertoli cells and expressed at aberrant levels in SCO testes. Some of these transcripts encode proteins required for the proper assembly of adherent and gap junctions at sites of contact with other cells, including spermatogonial stem cells (SSCs). Other transcripts encode GDNF, FGF8 and BMP4, known regulators of mouse SSCs. Thus, most SCO Sertoli cells can neither organize junctions at normal sites of cell-cell contact nor stimulate SSCs with adequate levels of growth factors. We propose that the critical deficits in Sertoli cell gene expression we have identified contribute to the inability of spermatogonial stem cells within small patches of spermatogenesis in some SCO testes to seed spermatogenesis to adjacent areas of tubule that are barren of spermatogenesis. Furthermore, we predict that one or more of these deficits in gene expression are primary causes of human SCO syndrome. |
format | Online Article Text |
id | pubmed-6508736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-65087362019-05-23 Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome Paduch, Darius A. Hilz, Stephanie Grimson, Andrew Schlegel, Peter N. Jedlicka, Anne E. Wright, William W. PLoS One Research Article Sertoli cell-only (SCO) syndrome is a severe form of human male infertility seemingly characterized by the lack all spermatogenic cells. However, tubules of some SCO testes contain small patches of active spermatogenesis and thus spermatogonial stem cells. We hypothesized that these stem cells cannot replicate and seed spermatogenesis in barren areas of tubule because as-of-yet unrecognized deficits in Sertoli cell gene expression disable most stem cell niches. Performing the first thorough comparison of the transcriptomes of human testes exhibiting complete spermatogenesis with the transcriptomes of testes with SCO syndrome, we defined transcripts that are both predominantly expressed by Sertoli cells and expressed at aberrant levels in SCO testes. Some of these transcripts encode proteins required for the proper assembly of adherent and gap junctions at sites of contact with other cells, including spermatogonial stem cells (SSCs). Other transcripts encode GDNF, FGF8 and BMP4, known regulators of mouse SSCs. Thus, most SCO Sertoli cells can neither organize junctions at normal sites of cell-cell contact nor stimulate SSCs with adequate levels of growth factors. We propose that the critical deficits in Sertoli cell gene expression we have identified contribute to the inability of spermatogonial stem cells within small patches of spermatogenesis in some SCO testes to seed spermatogenesis to adjacent areas of tubule that are barren of spermatogenesis. Furthermore, we predict that one or more of these deficits in gene expression are primary causes of human SCO syndrome. Public Library of Science 2019-05-09 /pmc/articles/PMC6508736/ /pubmed/31071133 http://dx.doi.org/10.1371/journal.pone.0216586 Text en © 2019 Paduch et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Paduch, Darius A. Hilz, Stephanie Grimson, Andrew Schlegel, Peter N. Jedlicka, Anne E. Wright, William W. Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title | Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title_full | Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title_fullStr | Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title_full_unstemmed | Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title_short | Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome |
title_sort | aberrant gene expression by sertoli cells in infertile men with sertoli cell-only syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6508736/ https://www.ncbi.nlm.nih.gov/pubmed/31071133 http://dx.doi.org/10.1371/journal.pone.0216586 |
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