The effect of imatinib administered in the prenatal period on testis development in rats

It was aimed to investigate the effects of imatinib exposure on testicular development during prenatal period in rats. Fifteen pregnant Sprague Dawley rats used in our study were divided into 5 groups; control group, prenatal 1-8. Imatinib-20 (20 mg/kg), Imatinib-40 (40 mg/kg), Imatinib-60 (60 mg/kg) and Imatinib-80 (80 mg/kg) groups were defined as imatinib on days. Prenatal 1-8. Although pregnancy continued when imatinib was given intraperitoneally on days, it was observed that the pregnancy did not continue in the imatinib-80 group. On the postnatal 60th day, young male rats were sacrificed. For histopathological and immunohistochemical analysis, testicular tissue was taken and followed in fixation solutions, staining was done by taking thin sections, and appropriate areas were photographed and evaluated. Sperm count was made in epididymal fluid. Serum and testis samples used in biochemical analysis were kept under suitable conditions and mRNA was isolated from tissue samples in molecular analyzes. All statistical data were evaluated. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group (p= 0,001), but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group (p= 0,01). In the measurement of TBARS level, the drug in the Imatinib-20 group increased oxidative stress in the testis (p = 0.014) and serum (p = 0.003), while in the Imatinib-60 group it caused a decrease in tissue (p = 0.027). Thiol measurements revealed a decrease in the testis (p= 0,080) and serum (p= 0.000) in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group (p= 0.005). Testosterone level measurements were significantly increased in Imatinib-20 group (p = 0.039) and Imatinib-60 groups (p = 0.007) compared to the control group, while the decrease in Imatinib-40 group was not significant. Molecular-level analyzes revealed that there was no statistically significant difference between the groups in terms of protamine and histone expression levels in testicular tissue. In conclusion, it has been shown that exposure to imatinib during prenatal period may cause histopathological and biochemical changes in testicular tissue, but there is no negative effect on nuclear maturation of germ cells during spermiogenesis. Keywords: Imatinib, C-kit, PDGF, testis, TUNEL, rat