Experimental evaluation of chemotherapy-induced models of testicular failure
V.Yu. Prokopyuk1,2, Yu.S. Akhatova1, T.V. Mykhalchuk1, D.V. Minukhina2, S.K. Smolyar3, O.S. Prokopyuk1
- Institute for Problems of Cryobiology and Cryomedicine of the NAS of Ukraine, Kharkiv, Ukraine
- Kharkiv National Medical University, Ukraine
- Municipal Non-Commercial Enterprise “City Clinical Multidisciplinary Hospital No. 5” of the Kharkiv City Council, Ukraine
DOI: https://doi.org/10.15407/fz72.01.061

Abstract
The increasing incidence of cancer among young individuals underscores the importance of preserving
reproductive function and improving experimental models for the study of chemotherapy-induced testicular
failure. The aim of this study was to conduct a comparative evaluation of cytostatic agents from different
pharmacological classes in a mouse model of testicular dysfunction. Male Balb/c mice were treated with
cyclophosphamide (250 mg/kg), doxorubicin (10 mg/kg), or cisplatin (10 mg/kg). Body weight, hemato-
logical parameters, survival, social activity, anxiety levels, and sperm parameters were assessed at 1, 4,
and 8 weeks post-treatment. Doxorubicin caused early and pronounced toxicity, including weight loss,
hematopoietic suppression, reduced sperm count, motility, and viability, along with an increased proportion
of abnormal forms as early as one week after administration. By week 4, complete aspermatogenesis was
observed, accompanied by persistent behavioral impairments and increased lethality, without recovery by
the end of the study. In the cyclophosphamide group, body weight and hematological parameters stabilized
within 4 weeks, although irreversible anxiety elevation and transient reduction in social activity were noted.
Oligospermia peaked at week 4, accompanied by decreased motility and viability, while sperm count and
morphology remained impaired up to week 8. Cisplatin demonstrated the mildest and predominantly revers-
ible effects. Body weight progressively increased, hematological alterations were moderate with subsequent
recovery, and social activity was generally preserved except for a transient decline at week 4. Anxiety levels
showed a decreasing trend, while moderate oligospermia was detected without significant morphological
abnormalities. By week 8, sperm count and motility showed marked improvement. In summary, cyclophos-
phamide represents the most suitable agent for modeling testicular failure with partial functional recovery,
doxorubicin induces irreversible gonadotoxicity, and cisplatin may be employed to study mild, reversible
forms of gonadal impairment.
Keywords:
cytostatics, chemotherapy, cyclophosphamide, doxorubicin, cisplatin, testicular failure, biomedical modeling
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