Clin Exp Reprod Med.  2022 Jun;49(2):93-100. 10.5653/cerm.2022.05218.

Impact of imatinib administration on the mouse ovarian follicle count and levels of intra-ovarian proteins related to follicular quality

Affiliations
  • 1Department of Obstetrics and Gynecology, Fertility Center of CHA Ilsan Medical Center, CHA University School of Medicine, Seoul, Republic of Korea
  • 2Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
  • 3Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

Abstract


Objective
The impact of imatinib, a tyrosine kinase inhibitor, on ovarian follicles and several proteins related to follicular function and apoptosis was investigated in mice.
Methods
Saline, cyclophosphamide (Cp; 50 or 75 mg/kg), or imatinib (7.5 or 15 mg/kg) was injected once intraperitoneally into female B6D2F1 mice (18 mice in each group). In multiple ovarian sections, the number of various types of follicles and the proportion of good-quality (G1) follicles were counted. The levels of six proteins (anti-Müllerian hormone [AMH], BCL-xL, BAX, acid sphingomyelinase [A-SMase], caspase-3, and α-smooth muscle actin [α-SMA]) within the whole ovaries were quantified using Western blots.
Results
Compared to the saline group, a significant reduction of the primordial follicle count was observed in the group treated with imatinib 7.5 and 15 mg/kg, as well as in the group treated with Cp 75 mg/kg. Administration of Cp significantly decreased the proportion of G1 primordial follicles, but administration of imatinib did not. No differences in the AMH, anti-apoptotic BCLX-L, pro-apoptotic BAX, and A-SMase levels in the ovarian tissues were observed among the five groups. However, caspase-3 and α-SMA levels were significantly higher in the imatinib and Cp groups than in the saline group.
Conclusion
The administration of imatinib to mice significantly reduced the primordial follicle count and increased the protein levels of caspase-3 and α-SMA. Our findings suggest that imatinib potentially exerts ovarian toxicity via apoptotic processes, similarly to Cp.

Keyword

Caspase; Cyclophosphamide; Imatinib; Primordial follicle; Tyrosine kinase inhibitor
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