Protecting spermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone‐releasing hormone analog leuprorelin

Abstract

Purpose : 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). Conclusion : The significant prophylactic effect ( P < 0.05) of LH-RH analog against doxorubicininduced spermatogonial apoptosis was observed in a stage specific manner by microscopic evaluation with TUNEL.

Ellagic acid and rosmarinic acid attenuate doxorubicin-induced testicular injury in rats

“…Thus, providing explanation for the parenchymal atrophy in the seminiferous tubules observed following doxorubicin use in the present histopathological examination . Our findings agree with earlier studies and can be attributed to oxidative stress and production of free radicals as a by‐product of doxorubicin metabolism. Free radicals cause membrane and macromolecule damage by lipid peroxidation .…”

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions, apoptosis, lipid peroxidation and sperm damages

“…Spermatogenic cells are targeted by cytotoxic agents because of their high mitotic activity. Damages in spermatogonia result in prolonged sterility or oligozoospermia (Howell and Shalet, 2001;Endo et al, 2003). The chance of recovery of spermatogenesis following cytotoxic insult, and also the extent and speed of recovery, are related to the agent used and the dose received.…”

“…ADR treatment is associated with decreased spermatogenic activity that characterized with damaged quality and quantity of spermatozoa. It has been reported that ADR treated rats have shown depletion in the number of spermatogonia, decrease in the percentage of motile sperm, and increase in sperm morphological abnormalities (Kato et al, 2001;Ateş ş ahin et al, 2006), apoptosis at specific stages of seminiferous epithelial cycle (Sjoblom et al, 1998;Shinoda et al, 1999;Endo et al, 2003) and decrease in testosterone concentrations (Ateş ş ahin et al, 2006) in rats. In addition, ADR causes severe degenerative changes, shrunken seminiferous tubules with decreased germ cells in testicular tissue (Ateş ş ahin et al, 2006).…”

Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats

“…Doxorubicin induced an increase in reactive oxygen species (ROS) levels or its direct effects on Leydig cell causing its impairment leading to a decrease in testosterone production (Endo et al, 2003;Ateşşahin et al, 2006). In this study, it was observed that the reason of the DOXinduced decreased testosterone concentration was mainly due to the damages in Leydig cells (Fig.…”