Doxorubicin-induced ovarian toxicity

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.

Dexrazoxane exacerbates doxorubicin-induced testicular toxicity

“…Mice were re-weighed and sacrificed 1 (7, 10, 9 and 15 mice respectively), 3 (8, 10, 10 and 12 mice respectively) or 6 months later (6,8,7 and 8 mice respectively). DXR chosen dose was similar to the dose used in our female gonadal toxicity study (Ben-Aharon et al 2010). DEX chosen dose was calculated according to the dose used in humans (USFDA 2005).…”

Toxicity effect of Auxemma oncocalyx fraction and its active principle oncocalyxone A on in vitro culture of caprine secondary follicles and in vitro oocyte maturation

“…More studies are therefore needed to discern the mechanism of action of both drugs. Recent studies have revealed that DXR induces ovarian toxicity, which was observed by a reduction in the ovulation rate and the size of the ovary (OKTEM; OKTAY, 2007;BEN-AHARON et al, 2010). DXR elicits apoptosis by various mechanisms in a variety of cells.…”

“…Doxorubicin (DXR) is one of the most commonly used drug (OKTEM;OKTAY, 2007) in the treatment of cancers of bladder, breast, lung, ovary, and other organs (CHOW et al, 2010); this drug transgresses the cell membrane and accumulates in both the nucleus mitochondria by inducing oxidative stress and chromosomal obliteration through the inhibition of topoisomerase II (MAILER;PETIRING, 1976). However, DXR induces ovarian toxicity by reducing the ovulation rate along with reducing the size of the ovary among other side effects (OKTEM;OKTAY, 2007;BEN-AHARON et al, 2010). The poor specificity of these drugs against tumor tissue highlights the need for developing new drugs with fewer side effects (OKTEM; OKTAY, 2007) and more specificity.…”

Chemotherapy-Related Amenorrhea in Breast Cancer: Review of the Main Published Studies, Biomarkers of Ovarian Function and Mechanisms Involved in Ovarian Toxicity

“…This is why in our laboratory, we will repeat the injections of cyclophosphamide in new experiments to try to observe apoptosis in mice ovaries. The studies of Meirow et al Meirow et al (2007) and Aharon Ben-Aharon et al (2010) hypothesized a combined mechanism of neovascularization and ovarian tissue scarring with a direct toxic effect on the primordial follicles. Personally, we think that additional processes that lead to ovarian damage and follicles loss after chemotherapy may be involved such as vascular complications and ischemic mechanisms.…”

“…These modes of injury were present in non-atrophic ovaries of patients that were not sterilized by chemotherapy. Ben Aharon and his coworkers Ben-Aharon et al (2010) evaluated the effects of doxocuribin (injected intraperitoneally) on mice ovaries. A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post-treatment.…”