Cargando…
Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection
An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%–87% of mice die when administered an intraperitoneal injection of 40 mg kg(−1). In the present study, h...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155790/ https://www.ncbi.nlm.nih.gov/pubmed/31187778 http://dx.doi.org/10.4103/aja.aja_41_19 |
_version_ | 1783522108351971328 |
---|---|
author | Xie, Yun Deng, Cun-Can Ouyang, Bin Lv, Lin-Yan Yao, Jia-Hui Zhang, Chi Chen, Hai-Cheng Liang, Xiao-Yan Sun, Xiang-Zhou Deng, Chun-Hua Liu, Gui-Hua |
author_facet | Xie, Yun Deng, Cun-Can Ouyang, Bin Lv, Lin-Yan Yao, Jia-Hui Zhang, Chi Chen, Hai-Cheng Liang, Xiao-Yan Sun, Xiang-Zhou Deng, Chun-Hua Liu, Gui-Hua |
author_sort | Xie, Yun |
collection | PubMed |
description | An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%–87% of mice die when administered an intraperitoneal injection of 40 mg kg(−1). In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg(−1)) on day 36 or a dose of 40 mg kg(−1) at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg(−1) busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg(−1) in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity. |
format | Online Article Text |
id | pubmed-7155790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-71557902020-04-21 Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection Xie, Yun Deng, Cun-Can Ouyang, Bin Lv, Lin-Yan Yao, Jia-Hui Zhang, Chi Chen, Hai-Cheng Liang, Xiao-Yan Sun, Xiang-Zhou Deng, Chun-Hua Liu, Gui-Hua Asian J Androl Original Article An ideal animal model of azoospermia would be a powerful tool for the evaluation of spermatogonial stem cell (SSC) transplantation. Busulfan has been commonly used to develop such a model, but 30%–87% of mice die when administered an intraperitoneal injection of 40 mg kg(−1). In the present study, hematoxylin and eosin staining, Western blot, immunofluorescence, and quantitative real-time polymerase chain reaction were used to test the effects of busulfan exposure in a mouse model that received two intraperitoneal injections of busulfan at a 3-h interval at different doses (20, 30, and 40 mg kg(−1)) on day 36 or a dose of 40 mg kg(−1) at different time points (0, 9, 18, 27, 36, and 63 days). The survival rate of the mice was 100%. When the mice were treated with 40 mg kg(−1) busulfan, dramatic SSC depletion occurred 18 days later and all of the germ cells were cleared by day 36. In addition, the gene expressions of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2), chemokine (C-X-C Motif) ligand 12 (CXCL12), and colony-stimulating factor 1 (CSF1) were moderately increased by day 36. A 63-day, long-term observation showed the rare restoration of endogenous germ cells in the testes, suggesting that the potential period for SSC transplantation was between day 36 and day 63. Our results demonstrate that the administration of two intraperitoneal injections of busulfan (40 mg kg(−1) in total) at a 3-h interval to mice provided a nonlethal and efficient method for recipient preparation in SSC transplantation and could improve treatments for infertility and the understanding of chemotherapy-induced gonadotoxicity. Wolters Kluwer - Medknow 2019-06-07 /pmc/articles/PMC7155790/ /pubmed/31187778 http://dx.doi.org/10.4103/aja.aja_41_19 Text en Copyright: ©The Author(s)(2019) http://creativecommons.org/licenses/by-nc-sa/4.0 This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Xie, Yun Deng, Cun-Can Ouyang, Bin Lv, Lin-Yan Yao, Jia-Hui Zhang, Chi Chen, Hai-Cheng Liang, Xiao-Yan Sun, Xiang-Zhou Deng, Chun-Hua Liu, Gui-Hua Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title | Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title_full | Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title_fullStr | Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title_full_unstemmed | Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title_short | Establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
title_sort | establishing a nonlethal and efficient mouse model of male gonadotoxicity by intraperitoneal busulfan injection |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155790/ https://www.ncbi.nlm.nih.gov/pubmed/31187778 http://dx.doi.org/10.4103/aja.aja_41_19 |
work_keys_str_mv | AT xieyun establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT dengcuncan establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT ouyangbin establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT lvlinyan establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT yaojiahui establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT zhangchi establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT chenhaicheng establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT liangxiaoyan establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT sunxiangzhou establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT dengchunhua establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection AT liuguihua establishinganonlethalandefficientmousemodelofmalegonadotoxicitybyintraperitonealbusulfaninjection |