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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0216586 |
| _version_ | 1831586386499600384 |
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| author | Darius A Paduch Stephanie Hilz Andrew Grimson Peter N Schlegel Anne E Jedlicka William W Wright |
| author_facet | Darius A Paduch Stephanie Hilz Andrew Grimson Peter N Schlegel Anne E Jedlicka William W Wright |
| author_sort | Darius A Paduch |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-17T21:35:28Z |
| format | Article |
| id | doaj.art-5c445acec69c46aa8420035924eb2e0b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T21:35:28Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5c445acec69c46aa8420035924eb2e0b2022-12-21T21:31:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01145e021658610.1371/journal.pone.0216586Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome.Darius A PaduchStephanie HilzAndrew GrimsonPeter N SchlegelAnne E JedlickaWilliam W WrightSertoli 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.https://doi.org/10.1371/journal.pone.0216586 |
| spellingShingle | Darius A Paduch Stephanie Hilz Andrew Grimson Peter N Schlegel Anne E Jedlicka William W Wright Aberrant gene expression by Sertoli cells in infertile men with Sertoli cell-only syndrome. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0216586 |
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