Clin Exp Reprod Med.  2020 Dec;47(4):269-276. 10.5653/cerm.2020.03755.

Impact of imatinib or dasatinib coadministration on in vitro preantral follicle development and oocyte acquisition in cyclophosphamide-treated mice

• Hong YH
• Kim SJ
• Kim SK
• Lee SC
• Jun JH
• Jee BC
• Kim SH

• KMID: 2509283
• DOI: http://doi.org/10.5653/cerm.2020.03755

Abstract

Objective
We investigated the impact of tyrosine kinase inhibitor (imatinib or dasatinib) coadministration with cyclophosphamide (Cp) on preantral follicle development in an in vitro mouse model.
Methods
Seventy-three female BDF1 mice were allocated into 4 experimental groups: group A, saline; group B, Cp (25 mg/kg); group C, Cp (25 mg/kg) and imatinib (7.5 mg/kg); and group D, Cp (25 mg/kg) and dasatinib (7.5 mg/kg). Preantral follicles were isolated and cultured in vitro up to 12 days. Final oocyte acquisition and spindle integrity of metaphase II (MII) oocytes were assessed. Levels of 17β-estradiol and anti-Müllerian hormone (AMH) in the final spent media were measured by enzyme-linked immunosorbent assays, and the mRNA levels of Star, Sod1, Mapk3, and Casp3 in the final follicular cells were quantified by real-time polymerase chain reaction.
Results
The percentage of MII oocytes per initiated follicle, the proportion of MII oocytes with normal spindles, and the 17β-estradiol level were similar in all four groups. The median AMH level in group B (7.74 ng/mL) was significantly lower than that in group A (10.84 ng/mL). However, the median AMH levels in group C (9.96 ng/mL) and group D (9.71 ng/mL) were similar to that in group A. The mRNA expression levels of Star, Sod1, Mapk3, and Casp3 were similar in all four groups.
Conclusion
Coadministration of imatinib or dasatinib with Cp could preserve AMH production capacity in this in vitro mice preantral follicle culture model, and it did not affect MII oocyte acquisition.

Keyword

Cyclophosphamide; Dasatinib; Imatinib; Oocyte; Tyrosine kinase