Doxorubicin-induced ovarian toxicity

Reproductive Biology and Endocrinology

Research

Ruth Shalgi¹  Lital Kuchinsky¹  Hadas Bar-Joseph¹  Galia Tzarfaty²  Salomon M Stemmer³  Irit Ben-Aharon³  Shulamith Rizel³ 

[1] Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Israel;Department of Radiology, Sheba Medical Center, Tel Hashomer, Israel;Institute of Oncology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah-Tiqva, Israel;

关键词: Doxorubicin;    Antral Follicle;    Primordial Follicle;    Ovulation Rate;    Premature Ovarian Failure;   

DOI  :  10.1186/1477-7827-8-20

 received in 2009-08-27, accepted in 2010-03-04,  发布年份 2010

来源: Springer

【 摘 要 】

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.

【 授权许可】

Unknown   
© Ben-Aharon et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.