Effect of imatinib co-administration on in vitro oocyte acquisition and subsequent embryo development in cyclophosphamide-treated mice

Abstract

Objective: To investigate the effect of imatinib co-administration on in vitro oocyte acquisition and subsequent embryo development in cyclophosphamide (Cp)-treated mice. Design: Experimental study. Materials and Methods: Female 4–5-week-old BDF1 mice (n=112) were injected with 5 IU eCG followed by 5 IU hCG 48 hours later and then oocytes were retrieved 14 hours later. They were grouped according to the dose of Cp and/or imatinib which were injected 24 hours prior to eCG injection (group 1: saline 0.1 mg/kg

group 2, 3, 4: Cp 25, 50, 75 mg/kg, group 5: imatinib 7.5mg/kg, group 6, 7, 8: Cp 25, 50, 75 with imatinib 7.5 mg/kg). Each number of mature, dead and total oocytes was counted. After in vitro fertilization, fertilization rate and percentage of blastocyst formation were assessed. Blastocyst cell numbers and percentage of apoptotic cells were assessed by TUNEL method. Meiotic spindle integrity within mature oocytes was also assessed Results: In the 25 and 50 mg/kg Cp group, imatinib co-administration significantly enhanced the percentage of mature oocytes (+16.4%, p<0.001 and +10.4%, p<0.02, respectively) and significantly decreased the percentage of dead oocytes (-25.9%, p<0.001 and -15.3%, p<0.001, respectively). Imatinib co-administration significantly enhanced the fertilization rate in the 50 mg/kg Cp group (+12.2%, p<0.05). The percentage of blastocysts formation and their cell number as well as the percentage of apoptotic cells was similar whether imatinib was co-administered or not. Spindle integrity within oocyte was significantly affected by the Cp treatment and was rescued by the imatinib co-administration. Conclusions: Imatinib co-administration prior to ovarian stimulation improved oocyte maturity and in vitro fertilization rate in Cp-treated mice. Spindle integrity within oocyte was well-conserved by the imatinib co-administration.