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Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F

Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possib...

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Autores principales: Xiong, Ji, Wang, Hu, Guo, Guangming, Wang, Shuzeng, He, Liqun, Chen, Haifeng, Wu, Ji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115959/
https://www.ncbi.nlm.nih.gov/pubmed/21698297
http://dx.doi.org/10.1371/journal.pone.0020751
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author Xiong, Ji
Wang, Hu
Guo, Guangming
Wang, Shuzeng
He, Liqun
Chen, Haifeng
Wu, Ji
author_facet Xiong, Ji
Wang, Hu
Guo, Guangming
Wang, Shuzeng
He, Liqun
Chen, Haifeng
Wu, Ji
author_sort Xiong, Ji
collection PubMed
description Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on spermatogenesis, we administered 4 groups of 4-week-old male mice with different doses of GTW. We found a dose-dependent decrease in the number of germ cells after 40 days of GTW treatment, and an increase in apoptotic cells from the low-dose to the high-dose group. During this same period the dimethylated level of histone H3 lysine 9 (H3K9me2) in GTW-treated testes germ cells declined. Additionally, spermatogonial stem cells (SSCs) from 6-day-old mice were isolated to evaluate the possible effect of GTW or triptolide on development of SSCs. We found a significantly higher incidence of apoptosis and lower dimethylation level of H3K9me2 in the SSCs of GTW or triptolide treatment than in controls. Thus, these data suggest that the GTW-induced apoptosis might be responsible for the fertility impairment in mice. This damage could be traced back to the early stages of spermatogenesis. GTW also affected the epigenetic modification of H3K9 in spermatogenesis. Molecular dynamics simulation suggested that triptolide and dimethylated or trimethylated H3K9 might have similar interaction mechanisms with EED (embryonic ectoderm development). These candidate activation mechanisms provide the first glimpse into the pathway of GTW-induced gonad toxicity, which is crucial for further research and clinical application.
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spelling pubmed-31159592011-06-22 Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F Xiong, Ji Wang, Hu Guo, Guangming Wang, Shuzeng He, Liqun Chen, Haifeng Wu, Ji PLoS One Research Article Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on spermatogenesis, we administered 4 groups of 4-week-old male mice with different doses of GTW. We found a dose-dependent decrease in the number of germ cells after 40 days of GTW treatment, and an increase in apoptotic cells from the low-dose to the high-dose group. During this same period the dimethylated level of histone H3 lysine 9 (H3K9me2) in GTW-treated testes germ cells declined. Additionally, spermatogonial stem cells (SSCs) from 6-day-old mice were isolated to evaluate the possible effect of GTW or triptolide on development of SSCs. We found a significantly higher incidence of apoptosis and lower dimethylation level of H3K9me2 in the SSCs of GTW or triptolide treatment than in controls. Thus, these data suggest that the GTW-induced apoptosis might be responsible for the fertility impairment in mice. This damage could be traced back to the early stages of spermatogenesis. GTW also affected the epigenetic modification of H3K9 in spermatogenesis. Molecular dynamics simulation suggested that triptolide and dimethylated or trimethylated H3K9 might have similar interaction mechanisms with EED (embryonic ectoderm development). These candidate activation mechanisms provide the first glimpse into the pathway of GTW-induced gonad toxicity, which is crucial for further research and clinical application. Public Library of Science 2011-06-15 /pmc/articles/PMC3115959/ /pubmed/21698297 http://dx.doi.org/10.1371/journal.pone.0020751 Text en Xiong 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xiong, Ji
Wang, Hu
Guo, Guangming
Wang, Shuzeng
He, Liqun
Chen, Haifeng
Wu, Ji
Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title_full Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title_fullStr Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title_full_unstemmed Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title_short Male Germ Cell Apoptosis and Epigenetic Histone Modification Induced by Tripterygium wilfordii Hook F
title_sort male germ cell apoptosis and epigenetic histone modification induced by tripterygium wilfordii hook f
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115959/
https://www.ncbi.nlm.nih.gov/pubmed/21698297
http://dx.doi.org/10.1371/journal.pone.0020751
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