Cisplatin and Doxorubicin Induce Distinct Mechanisms of Ovarian Follicle Loss; Imatinib Provides Selective Protection Only against Cisplatin

摘要: Purpose Chemotherapy treatment in premenopausal women has been linked to ovarian follicle loss and premature failure; the exact mechanism by which this occurs is uncertain. Here, two commonly used chemotherapeutic agents (cisplatin doxorubicin) were added a mouse ovary culture system, compare sequence of events that leads germ cell loss. The ability imatinib mesylate protect against cisplatin or doxorubicin-induced damage was also examined. Experimental design Newborn ovaries cultured for total six days, exposed agent on second day: allowed examination earliest stages development. Cleaved PARP TUNEL assess apoptosis following drug treatment. Imatinib cultures with doxorubicin determine any protective effect. Results Histological analysis treated showed oocyte-specific damage; comparison preferentially caused granulosa cells. expression significantly increased (16 fold, p<0.001) (3 p<0.01). staining gave little evidence primordial either drug. had significant effect cisplatin-induced (p<0.01) but not treatment. Conclusion Cisplatin both induced damage, markedly different pattern, protecting doxorubicin. Any designed block effects may need be specific drug(s) patient to.