In Vivo Models of Ovarian Toxicity

The success of cancer treatment results in female survivors who wrestle with long-term reproductive side effects of chemotherapy. An ideal ovoprotective drug would be mechanism-based, requiring increased knowledge of the action of chemotherapy drugs on the ovary. The strengths and weaknesses of relevant animal models in researching the mechanism of chemotherapy ovarian toxicity and developing ovoprotective therapies are discussed. Emerging in vivo rodent studies reveal that chemotherapeutic agents target multiple ovarian cell types. Most in vivo data assess either acute or long-term ovoprotection from a single chemotherapeutic agent, but direct cross-study efficacy comparisons are difficult due to disparate animal ages and endpoints. Nonetheless, in vivo proof-of-concept studies of some promising ovoprotectants in mice have led to normal offspring. Non-human primate models are necessary to evaluate chemotherapy-induced ovarian toxicity in vivo if the development of ovoprotective agents is to become a clinical reality. Future research on ovarian chemoprotection and design of novel chemotherapeutic agents that are not ovotoxic will transform clinical oncofertility practices for female cancer patients.