Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, but no significant change in atretic follicle abundance. We also observed IM-induced premature hatching, but no significant change in embryo-larvae survivability. However, we found significant IM-induced morphometric malformations. IM decreased expression of vegfaa and igf2a (two reproductive-, angiogenic-, and growth-related genes) in testes and ovaries. The results demonstrate IM can induce significant changes in critical reproductive endpoints and zebrafish as a suitable model organism to show effects of IM on reproduction. The findings suggest that TKI effects on reproductive success should be considered.
Digital Object Identifier (DOI)
Ahmadi, Nader; Samaee, Seyed-Mohammadreza; Yokel, Robert A.; and Tehrani, Aliasghar, "Imatinib Mesylate Effects on Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability and Development, and Related Genes" (2019). Pharmaceutical Sciences Faculty Publications. 183.