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Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice

PURPOSE: Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodi...

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Autores principales: Lee, Wan, Son, Yeonghoon, Jang, Hyosun, Bae, Min Ji, Kim, Jungki, Kang, Dongil, Kim, Joong Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society for Sexual Medicine and Andrology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412004/
https://www.ncbi.nlm.nih.gov/pubmed/25927059
http://dx.doi.org/10.5534/wjmh.2015.33.1.20
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author Lee, Wan
Son, Yeonghoon
Jang, Hyosun
Bae, Min Ji
Kim, Jungki
Kang, Dongil
Kim, Joong Sun
author_facet Lee, Wan
Son, Yeonghoon
Jang, Hyosun
Bae, Min Ji
Kim, Jungki
Kang, Dongil
Kim, Joong Sun
author_sort Lee, Wan
collection PubMed
description PURPOSE: Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation. MATERIALS AND METHODS: Male C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation. RESULTS: Rolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis. CONCLUSIONS: These protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice.
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spelling pubmed-44120042015-04-29 Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice Lee, Wan Son, Yeonghoon Jang, Hyosun Bae, Min Ji Kim, Jungki Kang, Dongil Kim, Joong Sun World J Mens Health Original Article PURPOSE: Pelvic irradiation for the treatment of cancer can affect normal cells, such as the rapidly proliferating spermatogenic cells of the testis, leading to infertility, a common post-irradiation problem. The present study investigated the radioprotective effect of rolipram, a specific phosphodiesterase type-IV inhibitor known to increase the expression and phosphorylation of the cyclic adenosine monophosphate response element-binding protein (CREB), a key factor for spermatogenesis, with the testicular system against pelvic irradiation. MATERIALS AND METHODS: Male C57BL/6 mice were treated with pelvic irradiation (2 Gy) and rolipram, alone or in combination, and were sacrificed at 12 hours and 35 days after irradiation. RESULTS: Rolipram protected germ cells from radiation-induced apoptosis at 12 hours after irradiation and significantly increased testis weight compared with irradiation controls at 35 days. Rolipram also ameliorated radiation-induced testicular morphological changes, such as changes in seminiferous tubular diameter and epithelial height. Additionally, seminiferous tubule repopulation and stem cell survival indices were higher in the rolipram-treated group than in the radiation group. Moreover, rolipram treatment counteracted the radiation-mediated decrease in the sperm count and mobility in the epididymis. CONCLUSIONS: These protective effects of rolipram treatment prior to irradiation may be mediated by the increase in pCREB levels at 12 hours post-irradiation and the attenuated decrease in pCREB levels in the testis at 35 days post-irradiation in the rolipram-treated group. These findings suggest that activation of CREB signaling by rolipram treatment ameliorates the detrimental effects of acute irradiation on testicular dysfunction and the related male reproductive functions in mice. Korean Society for Sexual Medicine and Andrology 2015-04 2015-04-23 /pmc/articles/PMC4412004/ /pubmed/25927059 http://dx.doi.org/10.5534/wjmh.2015.33.1.20 Text en Copyright © 2015 Korean Society for Sexual Medicine and Andrology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Lee, Wan
Son, Yeonghoon
Jang, Hyosun
Bae, Min Ji
Kim, Jungki
Kang, Dongil
Kim, Joong Sun
Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title_full Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title_fullStr Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title_full_unstemmed Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title_short Protective Effect of Administered Rolipram against Radiation-Induced Testicular Injury in Mice
title_sort protective effect of administered rolipram against radiation-induced testicular injury in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412004/
https://www.ncbi.nlm.nih.gov/pubmed/25927059
http://dx.doi.org/10.5534/wjmh.2015.33.1.20
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