C-kit expression in spermatogonia damaged by doxorubicin exposure in mice

Abstract

Aim: The purpose of this study was to assess the relationship between chronically impaired spermatogenesis induced by exposing mice to doxorubicin (DXR) and expression of the infertility factor c-kit.

Method: Eight-week-old male Institute for Cancer Research (ICR) mice were intraperitoneally treated with DXR (0.15 mg/kg, DXR group) or saline (0.15 mg/kg, control group) twice weekly for five weeks and were killed 14 weeks after initial exposure. The animals were sacrificed and bilateral testes were removed and weighed. The testes were stored for the mRNA assay and were fixed for immunohistochemistry. Some testicular samples were fixed in 10% formalin for histopathological examination.

Results: Testicular weight (67.6 ± 9.7 mg, P < 0.05), sperm motility (18 ± 6.0%, P < 0.05) and the fertilization rate (2-to-16-cell embryos, 5%; P < 0.05) were significantly lower in the DXR group than in the control group. In the DXR group there was severe tissue damage from the spermatogonia onward, and the Sertoli cell ratio was lower in the DXR group than in the control group (38% vs. 9%, P < 0.05). In addition, there was a decrease in c-kit protein expression, and the amount of c-kit messenger ribonucleic acid (mRNA) expression according to a semiquantitative method was also decreased.

Conclusion: Expression of c-kit in the mice with chronically impaired spermatogenesis induced by long-term, low-dose administration of DXR correlated with the decrease in the number of spermatogonia.