EFFECT OF IMATINIB ON THE OOGENESIS AND PITUITARY-OVARY HORMONAL AXIS IN FEMALE WISTAR RAT

Abstract

Background: Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATP) that potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Arg and c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy. We tested the effect of imatinib on the ovarian histological structure and the concentration of estrogen and progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum of female Wistar rats. Materials and Methods: Two groups of rats (180 ± 15 grams) were gavaged with doses of 50 and 100 mg/kg body weight imatinib dissolved in distilled water for 14 days. The control group received sterile water. On day 7, after termination of the treatment, blood serum concentration was measured with the radioimmunoassay (RIA) method. Also, sections (5 μm thick) of ovaries stained with hematoxylin and eosin (H&E) were investigated histologically. Results: Progesterone concentration in the experimental groups was increased (p<0.001), estrogen and FSH concentrations were decreased (p<0.01), and the LH concentration decreased but was not statistically different in comparison with the control group. The weight of ovaries and number of atretic follicles in the experimental groups was increased compared with the control group (p<0.05). The diameter of corpus lutea were increased but the number of corpus lutea decreased in both experimental groups (p<0.01). Conclusion: These findings suggest that administration of imatinib may have profound effects on female fertility.