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Imatinib mesylate effects on zebrafish reproductive success: Gonadal development, gamete quality, fertility,

Nader Ahmadi1, Seyed-Mohammadreza Samaee1, Robert A Yokel2

  • 1Aquatic Lab, Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia 165, Iran.

Toxicology and Applied Pharmacology
|July 7, 2019
PubMed

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.

Keywords:
ImatinibReproductionVegfaaZebrafishigf2a

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