Related Experiment Video
Updated: Mar 30, 2026
Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice
Published on: April 1, 2015
Gonadotoxic effects of busulfan in two strains of mice
Karina Gutierrez1, Werner G Glanzner1, Raiza O Chemeris1
1Laboratory of Biotechnology and Animal Reproduction-BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
Abstract:
Busulfan is a chemotherapy drug that has side effects on spermatogonial stem cells (SSC). The effects of bulsufan treatment on male germ cells and fertility vary significantly between individuals. In this study, we have used molecular, cellular and histopathology approaches to investigate the effects of a single intraperitoneal dose of busulfan (40mgkg(-1)) in two mice strains, Balb/C and Swiss, at two different periods after treatment, 30 and 90 days. Testicular degeneration was observed in both Balb/C and Swiss mice after busulfan injection. Interestingly, testicular functions and fertility recovered spontaneously post busulfan treatment in Swiss mice, but not in Balb/C mice. Abnormal fertility induced by busulfan in Balb/C mice was associated with altered seminiferous tubules, sperm morphology and transcript levels of Nanos2, Nanos3, Gdnf and Plzf genes. These findings revealed that SSC of Balb/C mice are more sensitive to the toxic effects of busulfan then those of Swiss mice.
Insights
Busulfan chemotherapy impacts male fertility by damaging spermatogonial stem cells (SSC). Swiss mice fertility recovered, unlike Balb/C mice, indicating strain-dependent sensitivity to busulfan
Area of Science:
- Reproductive biology
- Toxicology
- Genetics
Background:
- Busulfan is a chemotherapy agent with known toxicity to spermatogonial stem cells (SSC).
- Individual variability in response to busulfan treatment affects male germ cells and fertility.
- Understanding strain-specific responses is crucial for assessing reproductive risks.
Purpose of the Study:
- To investigate the differential effects of busulfan on male germ cells and fertility in Balb/C and Swiss mice.
- To determine the recovery patterns of testicular function and fertility post-busulfan exposure.
- To identify molecular markers associated with busulfan-induced infertility.
Main Methods:
- Administration of a single intraperitoneal dose of busulfan (40mg/kg) to Balb/C and Swiss mice.
- Evaluation at 30 and 90 days post-treatment using molecular, cellular, and histopathological analyses.
- Assessment of testicular degeneration, sperm morphology, and gene expression (Nanos2, Nanos3, Gdnf, Plzf).
Main Results:
- Testicular degeneration observed in both mouse strains post-busulfan treatment.
- Spontaneous recovery of testicular function and fertility in Swiss mice, but not in Balb/C mice.
- Balb/C mice exhibited altered seminiferous tubules, sperm morphology, and gene expression linked to infertility.
Conclusions:
- Balb/C mice exhibit higher sensitivity of spermatogonial stem cells (SSC) to busulfan toxicity compared to Swiss mice.
- Strain-specific differences significantly influence the recovery of male fertility after busulfan exposure.
- Altered gene expression in Balb/C mice correlates with persistent busulfan-induced infertility.
