Protecting spermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone-releasing hormone analog leuprorelin.
OBJECTIVE
The present study was performed to investigate the protective effect of leuprorelin (LH-RH analog), on spermatogonia apoptosis induced by doxorubicin (DXR) in the Sprague-Dawley rat model.


METHODS
Twenty-four adult male rats were divided into the following four groups: (i) control group; (ii) group given doxorubicin (intravenous injection, 8 mg/kg); (iii) group given leuprorelin (subcutaneous injection, 3 mg/kg); and (iv) group given both doxorubicin (intravenous injection, 8 mg/kg) and leuprorelin (subcutaneous injection, 3 mg/kg). Evaluation for quantification of apoptotic spermatogonia was made by the ratio of TUNEL-labeled spermatogonia versus 100 Sertoli cells in each seminiferous tubule. Two hundred seminiferous tubules of each rat were assessed.


RESULTS
The ratio of apoptotic spermatogonia versus 100 Sertoli cells at stages II-IV of the groups given DXR (groups 2 and 4) were significantly higher than those of the other groups. However, the value at stages II-IV of the group given both DXR and leuprorelin (group 4) was significantly lower than that of the group given DXR (group 2).


CONCLUSIONS
The significant prophylactic effect (P < 0.05) of LH-RH analog against doxorubicin-induced spermatogonial apoptosis was observed in a stage specific manner by microscopic evaluation with TUNEL.
Endo
Fumiyasu
F
Department of Urology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. endo@tmch.or.jp
Manabe
Fumio
F
Takeshima
Hitoshi
H
Akaza
Hideyuki
H
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D016729:Leuprolide / Q000494:pharmacology*; D008297:Male; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013093:Spermatogonia / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013739:Testosterone / Q000032:analysis
D013739:Testosterone; D004317:Doxorubicin; D016729:Leuprolide