Kerr et al. 1 report that imatinib does not protect primordial oocytes from cisplatin-induced apoptosis. This stands in contrast with the results of a recent report from our group in Nature Medicine2. Furthermore, Kerr et al. 1 claim that imatinib causes oocyte death, possibly by blocking the tyrosine kinase activity of the stem cell factor receptor c-Kit, which is considered crucial for oocyte survival3. They state that they find no support for a new use for imatinib aimed at preserving the follicle reserve during cancer therapy. While attempting to reconcile the contradictory outcomes of their study and ours, we noticed that Kerr et al. 1 used a hospital-grade cisplatin solution (cisplatin-HG) commonly used in cancer therapy. In comparing the effects on cell line and oocyte survival of cisplatin-HG and Sigma cisplatin (which we used in our original report2), we observed that the latter is consistently less effective in inducing cell death if compared to apparently equivalent solutions of cisplatin-HG (Teva, 1 mg ml-1)(Supplementary Fig. 1). This may be due to the low solubility of Sigma cisplatin in PBS at concentrations around 1 mg ml-1.

Therefore, we repeated some crucial experiments using cisplatin-HG at a dose (2.5 mg per kg body weight) that, according to the titration curve (Supplementary Fig. 1c), induces the same effect caused by 5.0 mg per kg body weight of Sigma cisplatin, the concentration used in our original report. The results of these new experiments confirm that imatinib prevents oocytes of primordial and primary follicles from degeneration induced by cisplatin-HG in vivo (Fig. 1a, b). We also clearly observed oocyte protection ex vivo, both on ovary fragments cultured in the presence of cisplatin for 24 h (Fig. 1c, d) and on intact gonads, as evaluated by TUNEL staining (Fig. 1e). In addition, as in our original report2, we did not observe any significant toxic effect on oocytes by imatinib alone either in vivo or ex vivo at a similar range of concentrations (or even higher) to those reported by Kerr et al. 1 (in vivo: 7.5–30 mg per kg body weight Supplementary Fig. 2; ex vivo: 1 mM–10 mM, Fig. 1c–e). Notably, imatinib used at therapeutic doses, which are higher than those used in our studies, has no impact on folliculogenesis or spermatogenesis in a leukemia mouse model4.