Long-term effects of cytostatic agents on germ cells of testicular tissue (experimental study)

Abstract

Currently, cytostatic drugs are widely used not only in cancer treatment, but also in the treatment of autoimmune infammatory diseases. A favorable prognosis of the disease, ability to reproduce, young age and the absence of children serve as an incentive to decide on the need for childbearing. There is concern, that the mutagenic effects of chemotherapy in germ cells, the ability to induce epigenetic changes in them, may have phenotypic manifestations in offspring. Conception in the early stages after treatment (impact on mature and differentiating germ cells) has been proven to increase the risk of defective offspring. Data on the health of the offspring of patients conceived in the long term after treatment (impact on stem spermatogenic cells) are contradictory. The aim of the study was to assess long-term toxic effects of cytostatic drugs in the male rat offspring copulated in terms corresponding to the effect on stem spermatogonial cells (SSCs). Material and Methods. The experiments were carried out on autobred male Wistar rats (n=140), aged 2.5 months, 70 of which made up the group of intact animals. The effect of cytostatic drugs (etoposide, irinotecan, cisplatin, carboplatin, methotrexate, farmorubicin, and paclitaxel) injected 3 and 6 months before mating was assessed on the offspring of intact female and male rats. Results. The male rat offspring treated with cytostatic drugs was found to be viable. Gross external developmental anomalies were detected in 2 cases. In several offspring, a slowdown in physical development, decrease in the rate of formation of sensory-motor refexes and learning ability were observed. The most toxic drugs were etoposide and paclitaxel. Conclusion. The offspring of rats treated with cytostatic drugs in terms corresponding to the effect on the SSCs is at risk. The degree of severity of long-term effects varies signifcantly and depends on the type of the drugs used. A decrease in the ability to learn is the most frequently detected abnormalities in offspring. Judging by the timing of conception after cytostatic exposure, a signifcant increase in the period of time after the administration of the drug before mating is not always justifed.

Keywords

• cytotoxic drugs
• genotoxicity
• speratogonial stem cells
• offspring