Simulation of spermatogenesis disorders with chemotherapeutic agents -cisplatin and doxorubicin

Introduction. Cisplatin and Doxorubicin have pronounced toxic effects on spermatogenesis. Modeling of spermatogenesis disorders using these drugs can become convenient and relevant when conducting preclinical studies to assess the specific activity of new drugs for the treatment of toxic cases of male infertility. Objective. To evaluate the possibility of using Cisplatin and Doxorubicin for spermatogenesis disorders in vivo experiments. Materials and methods. In our study a model of spermatogenesis disorders caused by Cisplatin and doxorubicin was tested in mature male Wistar rats and mice of the C57BL/6 breed group. Cisplatin was administered intraperitoneally once at doses of 1 mg/kg, 2 mg/kg, 3 mg/kg and 4 mg/kg (2 rats in each group). The severity of spermatogenesis disorders was evaluated on the 14th and 28th days after administration. With multiple regimens, cisplatin was administered at a dose of 4 mg/kg for 3-5 days (8 rats per group). Doxorubicin was administered intraperitoneally at doses of 1,5 mg/kg and 3 mg/kg (5 mice in each group). The severity of spermatogenesis disorders was evaluated on the 35th day. The comparison of drug use modes was carried out using the Mann-Whitney U-test. Results. A single administration of Cisplatin did not lead to a violation of spermatogenesis. Multiple administration of Cisplatin caused severe general toxicity and animal lethality, and the maximum percentage of damaged tubules was only 9.1%. Doxorubicin in all used doses caused severe structural disorders, edema and spermatogenesis disorders in almost 100% of tubules. Conclusion. Using of Doxorubicin is reasonable for gonadotoxic effect modeling due to the long-term spermatoxic effects along with lower animal lethality. Thus, Doxorubicin model can be useful for evaluation of specific pharmacological activity of potential drugs - regeneration stimulants for the treatment of male infertility.