Abstract
Objective:Tyrosine kinase inhibitors may have deleterious effects on spermatogenesis or folliculogenesis, resulting in male or female subfertility. The aim of this study is to determine the effect of nilotinib, which is used routinely to treat chronic myeloid leukemia, on spermatogenesis and folliculogenesis by using histopathological parameters.Materials and Methods:Ten male and ten female mice were orally treated with nilotinib at 20 mg/kg body weight dissolved in drinking water daily for 2 months.Results:When compared with the control group, a statistically significant decrease was demonstrated in the total follicle numbers of the female mice in the nilotinib group (268±110 vs. 170±60; p=0.03). Active spermatogenesis was observed in each tubule sample taken from the mice in the control and nilotinib groups. Spermatogenic activity was similar in the two groups.Conclusion:We have demonstrated that even though spermatogenesis is preserved, folliculogenesis is inhibited by the usage of a continuous nilotinib treatment dose in chronic myeloid leukemia.
Highlights
The nilotinib molecule (AMN107) was first described in 2005 by Weisberg et al [1]
We have demonstrated that even though spermatogenesis is preserved, folliculogenesis is inhibited by the usage of a continuous nilotinib treatment dose in chronic myeloid leukemia
On the basis of these findings, we propose that continuous nilotinib treatment may affect folliculogenesis and spermatogenesis in a healthy mouse model
Summary
The nilotinib molecule (AMN107) was first described in 2005 by Weisberg et al [1]. It is a new imatinib-based aminopyrimidine that inhibits BCR-Abl (breakpoint cluster region-Abelson) signalization in the same way that imatinib does [2]. It inhibits BCR-Abl, and other tyrosine kinases such as c-kit, platelet-derived growth factor receptor A/B (PDGFR A/B), Arg (Abelson-related gene), and c-fms (colony-stimulating factor-1 receptor). Stem cell factor (SCF)/c-kit is expressed in human ovaries during follicular development, and during inhibition with anti-c-kit antibodies and c-kit receptor antagonists, the number of atretic. There are reported cases of healthy deliveries in the literature where one of the parents was undergoing imatinib treatment
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