A team of researchers from the University of South Carolina Arnold School of Public Health Department of Environmental Health Sciences and Department of Microbiology and Immunology have completed a study on the effects of doxorubicin, a chemical used in chemotherapy, on the ovaries. The research was led by assistant professor Dr. Shuo Xiao and published in Toxicology and Applied Pharmacology.
“Ovarian toxicity and infertility are major side effects of cancer therapy in young female cancer patients,” says Dr. Xiao. “We and others have previously demonstrated that doxorubicin, one of the most widely used chemotherapeutic chemicals, has a dose-dependent toxicity on growing follicles; however, it is not fully understood if the primordial follicles are the direct or indirect target of doxorubicin.”
The researchers investigated the effect of doxorubicin on the developmental stages of follicles. They also sought to determine the impact of this chemical on primordial follicle survival, activation and development and compared the impact of age on doxorubicin-induced ovarian toxicity.
The authors found that doxorubicin primarily damaged granulosa cells in growing follicles and oocytes in primordial follicles and doxorubicin-induced growing follicle apoptosis was associated with the primordial follicle overactivation. Their data also revealed that doxorubicin also directly promoted primordial follicle death and the DNA damage-TAp63α-C-CASP3 pathway was involved in DOX-induced primordial follicle oocyte apoptosis.
“These results demonstrate that doxorubicin obliterates ovarian reserve through both primordial follicle atresia and overactivation and the doxorubicin-induced ovarian toxicity is age dependent,” Dr. Xiao says.Tags: Friday Letter Submission, Publish on November 08