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Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes
Spermatogenesis is a process within the testis that leads to the production of spermatozoa. It is based on a population of spermatogonial stem cells, which have the capacity to self-renew and to differentiate throughout life to ensure the functions of reproduction are maintained. Male fertility diso...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472455/ https://www.ncbi.nlm.nih.gov/pubmed/34572051 http://dx.doi.org/10.3390/cells10092403 |
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author | Thirouard, Laura Holota, Hélène Monrose, Mélusine Garcia, Manon De Haze, Angélique Saru, Jean-Paul Caira, Françoise Beaudoin, Claude Volle, David H. |
author_facet | Thirouard, Laura Holota, Hélène Monrose, Mélusine Garcia, Manon De Haze, Angélique Saru, Jean-Paul Caira, Françoise Beaudoin, Claude Volle, David H. |
author_sort | Thirouard, Laura |
collection | PubMed |
description | Spermatogenesis is a process within the testis that leads to the production of spermatozoa. It is based on a population of spermatogonial stem cells, which have the capacity to self-renew and to differentiate throughout life to ensure the functions of reproduction are maintained. Male fertility disorders are responsible for half of the cases of infertility in couples worldwide. It is well known that cancer treatments are associated with reversible or irreversible fertility disorders. Busulfan (Bu) is an alkylating agent that significantly inhibits spermatogenesis. The present study relied on a combination of in vivo and in vitro approaches as well as RNAseq analysis to characterize the effects of Bu, in which mouse testes were used as a model. An in silico analysis revealed that many of the Bu-modulated genes are potentially regulated by the SIN3 Transcription Regulator Family Member A (SIN3A) and E2F Transcription Factor (E2F) families of transcription factors. The results demonstrate that the deregulated genes function in processes related to the cell cycle, DNA repair, and cell death mechanisms, including the Tumor Protein 53 (TP53) pathway. This reinforces the role of the TP53 signaling pathway as a major player in Bu effects. In addition, Bu altered the patterns of mRNA accumulation for various genes in undifferentiated spermatogonia. This work provides significant insight into the kinetics and impacts of busulfan, which could pave the way for developing strategies to minimize the impact of chemodrugs and, thus, could lead to germ cell lineage regeneration following anticancer treatments. |
format | Online Article Text |
id | pubmed-8472455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84724552021-09-28 Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes Thirouard, Laura Holota, Hélène Monrose, Mélusine Garcia, Manon De Haze, Angélique Saru, Jean-Paul Caira, Françoise Beaudoin, Claude Volle, David H. Cells Article Spermatogenesis is a process within the testis that leads to the production of spermatozoa. It is based on a population of spermatogonial stem cells, which have the capacity to self-renew and to differentiate throughout life to ensure the functions of reproduction are maintained. Male fertility disorders are responsible for half of the cases of infertility in couples worldwide. It is well known that cancer treatments are associated with reversible or irreversible fertility disorders. Busulfan (Bu) is an alkylating agent that significantly inhibits spermatogenesis. The present study relied on a combination of in vivo and in vitro approaches as well as RNAseq analysis to characterize the effects of Bu, in which mouse testes were used as a model. An in silico analysis revealed that many of the Bu-modulated genes are potentially regulated by the SIN3 Transcription Regulator Family Member A (SIN3A) and E2F Transcription Factor (E2F) families of transcription factors. The results demonstrate that the deregulated genes function in processes related to the cell cycle, DNA repair, and cell death mechanisms, including the Tumor Protein 53 (TP53) pathway. This reinforces the role of the TP53 signaling pathway as a major player in Bu effects. In addition, Bu altered the patterns of mRNA accumulation for various genes in undifferentiated spermatogonia. This work provides significant insight into the kinetics and impacts of busulfan, which could pave the way for developing strategies to minimize the impact of chemodrugs and, thus, could lead to germ cell lineage regeneration following anticancer treatments. MDPI 2021-09-13 /pmc/articles/PMC8472455/ /pubmed/34572051 http://dx.doi.org/10.3390/cells10092403 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Thirouard, Laura Holota, Hélène Monrose, Mélusine Garcia, Manon De Haze, Angélique Saru, Jean-Paul Caira, Françoise Beaudoin, Claude Volle, David H. Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title | Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title_full | Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title_fullStr | Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title_full_unstemmed | Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title_short | Analysis of the Reversible Impact of the Chemodrug Busulfan on Mouse Testes |
title_sort | analysis of the reversible impact of the chemodrug busulfan on mouse testes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472455/ https://www.ncbi.nlm.nih.gov/pubmed/34572051 http://dx.doi.org/10.3390/cells10092403 |
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