Protection of spermatogenesis against cytotoxic effects of two chemotherapeutic drugs by temporary testicular blood flow interruption in the ram.
Temporary interruption of the testicular blood flow for 1 h after injection of cytostatic drugs has a protective effect on spermatogenesis. This was shown in experiments in which spermatogenesis was evaluated at four weeks after a single intravenous injection of Adriblastina (ADR; doxorubicin hydrochloride) or Mitomycin-C-kyowa (MIT). Interruption of the blood flow was performed by inflation of an occluder implanted around the testicular artery. The animals were killed and histological sections prepared 4 weeks after treatment. In all drug-treated animals spermatids were near absence and spermatocytes were decreased in number. Therefore, even after occlusion of the blood flow, the drug doses were high enough to kill not only large numbers of differentiating spermatogonia but also stem cells. The response of the stem cells to the treatments was evaluated by counting the numbers of A spermatogonia per 100 Sertoli cells in the different groups. Normal numbers of these cells were found after both MIT and ADR, indicating that the stem cell population had responded to the initial cell loss by extra proliferation. However, significantly higher numbers of A spermatogonia were found in the drug-treated animals in which the testicular blood flow was interrupted for 1 h. This indicates that occlusion of the blood flow to the testis for 1 h results in a faster recovery of spermatogenesis than after drug treatment alone.
van Vliet
J
J
Department of Anatomy, School of Veterinary Medicine, State University, Utrecht, The Netherlands.
de Rooij
D G
DG
Wensing
C J
CJ
Bootsma
A L
AL
D000818:Animals; D003250:Constriction; D004317:Doxorubicin / Q000633:toxicity*; D005069:Evaluation Studies as Topic; D007511:Ischemia / Q000473:pathology; D008297:Male; D016685:Mitomycin / Q000633:toxicity*; D009845:Oligospermia / Q000139:chemically induced / Q000517:prevention & control; D012039:Regional Blood Flow; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012756:Sheep; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology
D016685:Mitomycin; D004317:Doxorubicin