Long-term imatinib treatment reduces spermatogenic cell proliferation in juvenile rat testes

Background: Long-term tyrosine kinase inhibitor (TKI) “targeted” treatment in pediatric patients with chronic myeloic leukemia reveals multiple off-target side effects. Specifically in testes, TKIs signaling cascades necessary for spermatogenesis are inhibited but the detailed action is not yet fully understood. Therefore, we investigated testicular tissue under TKI exposure in a juvenile rat model. Methods: Growing Wistar rats (age: 4 weeks (w)) were exposed over 10 w to imatinib (IM) or dasatinib (DASA) at different concentrations (low dose [LD], high dose [HD], intermittent high dose [ID]). At prepubertal (ag…