Related Experiment Video
Updated: May 17, 2026
Functional Assessment of Kinesin-7 CENP-E in Spermatocytes Using In Vivo Inhibition, Immunofluorescence and Flow Cytometry
Published on: December 28, 2021
C-kit expression in spermatogonia damaged by doxorubicin exposure in mice
Reiko Tanigaki1, Kou Sueoka, Hiroto Tajima
1Department of Obstetrics and Gynaecology, Keio University School of Medicine, Shinjuku-ku Shinanomachi 35, Tokyo 160-0016, Japan. rtanigaki@yahoo.co.jp
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.
Insights
Doxorubicin (DXR) exposure in mice significantly reduced testicular weight, sperm motility, and fertilization rates. This impairment in spermatogenesis correlated with decreased c-kit expression, a key infertility factor.
Area of Science:
- Reproductive toxicology
- Cancer research
- Molecular biology
Background:
- Doxorubicin (DXR) is a chemotherapy agent with known reproductive toxicity.
- Spermatogenesis is a complex process crucial for male fertility.
- C-kit is a tyrosine kinase receptor implicated in spermatogenesis and male infertility.
Purpose of the Study:
- To investigate the relationship between DXR-induced impaired spermatogenesis and c-kit expression in mice.
- To assess the impact of chronic low-dose DXR exposure on male reproductive parameters.
Main Methods:
- Male ICR mice were treated with DXR or saline twice weekly for five weeks.
- Testicular weight, sperm motility, and fertilization rates were evaluated.
- Histopathological examination, immunohistochemistry, and mRNA assays were performed to assess c-kit expression and tissue damage.
Main Results:
- DXR treatment significantly reduced testicular weight, sperm motility, and fertilization rates.
- Severe testicular tissue damage, including a decreased Sertoli cell ratio, was observed in DXR-treated mice.
- A significant decrease in both c-kit protein and mRNA expression was noted in the DXR group.
Conclusions:
- Chronic low-dose DXR administration induces impaired spermatogenesis in mice.
- Decreased c-kit expression is associated with DXR-induced testicular damage and reduced spermatogonia count.
- C-kit expression levels correlate with the severity of spermatogenesis impairment.
