PUBLICATION
Imatinib mesylate effects on zebrafish reproductive success: Gonadal development, gamete quality, fertility, embryo-larvae viability and development, and related genes
- Authors
- Ahmadi, N., Samaee, S.M., Yokel, R.A., Tehrani, A.
- ID
- ZDB-PUB-190707-4
- Date
- 2019
- Source
- Toxicology and applied pharmacology 379: 114645 (Journal)
- Registered Authors
- Keywords
- Imatinib, Reproduction, Vegfaa, Zebrafish, igf2a
- MeSH Terms
-
- Animals
- Embryo, Nonmammalian/drug effects
- Embryonic Development/drug effects
- Female
- Fertility/drug effects
- Gene Expression/drug effects
- Gonads/drug effects*
- Gonads/growth & development
- Imatinib Mesylate/toxicity*
- Larva/drug effects
- Larva/growth & development
- Male
- Reproduction/drug effects*
- Sperm Motility/drug effects
- Spermatozoa/drug effects
- Zebrafish/physiology
- PubMed
- 31278918 Full text @ Tox. App. Pharmacol.
- CTD
- 31278918
Citation
Ahmadi, N., Samaee, S.M., Yokel, R.A., Tehrani, A. (2019) Imatinib mesylate effects on zebrafish reproductive success: Gonadal development, gamete quality, fertility, embryo-larvae viability and development, and related genes. Toxicology and applied pharmacology. 379:114645.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping