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


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.
Department of Urology, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea. ; Medstar Washington Hospital Center, Georgetown University School of Medicine, Washington, DC, USA.
Wan
W
Lee
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.
Yeonghoon
Y
Son
Graduate School of Bio-Applications and System Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan.
Hyosun
H
Jang
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.
Min Ji
MJ
Bae
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea.
Jungki
J
Kim
Department of Urology, Inje University College of Medicine, Busan, Korea.
Dongil
D
Kang
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, Korea. ; College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
Joong Sun
JS
Kim
Cyclic AMP response element-binding protein; Radiation; Rolipram; Testis