Abstract
BackgroundYoung cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries.MethodsFemale mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin.ResultsA single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment.ConclusionsOur results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.
Highlights
Young cancer patients may occasionally face infertility and premature gonadal failure
Ovulation rate We studied the effect of a single injection of doxorubicin (10 mg/kg) on ovulation rate in 7-8 weeks old ICR female mice
The effect of in vivo doxorubicin administration on ovulation rate Doxorubicin-treated female mice were injected with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) to induce superovulation
Summary
Young cancer patients may occasionally face infertility and premature gonadal failure. Recent advances in cancer therapy have improved the long-term survival of young cancer patients who may face iatrogenic infertility and premature gonadal failure [1]. The need for tumor eradication in these patients is clear, the long-term effects of chemotherapy, observed on non-target tissues such as ovaries, are substantial and raise concern and potential health risks in women surviving diseases as breast cancer, Hodgkin’s disease and leukemia. In the current study we have established a platform of in vivo imaging for investigating the short and long term effects of doxorubicin on the ovaries. We have characterized the pattern of mice ovarian toxicity, induced following an in vivo administration of doxorubicin. Our results may indicate a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size due to possible acute ovarian insult
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