BMC Seminar: Monday, 27th March at 12:25, Room 343, Læknagarður
Speaker: Dr. Agnes Stefánsdóttir, Centre for Integrative Physiology, University of Edinburgh
Title: How do chemotherapy drugs affect the mouse ovary in vitro?
Cancer treatments where chemotherapeutic agents are used to treat a tumour are often gonadotoxic, potentially resulting in life-long infertility. Given that the long-term survival rates of cancer patients are continually rising, patients’ fertility problems have become of a greater concern in recent years. This is particularly the case for younger survivors of childhood cancers who may be rendered infertile before they have even reached puberty. Furthermore, cancer is diagnosed in 1-2 out of every 1,000 pregnant women, with chemotherapy agents being considered safe to administer during second and third trimesters of pregnancy, with follow-up studies indicating that overall health outcomes of children exposed to chemotherapy in utero after the first trimester have been comparable to that of unexposed children of the same age. There has not been a single study, however, reporting on the potential effects of chemotherapy agents on the reproductive systems of these children. There is therefore a distinct lack of information on the long-term effects of chemotherapy treatment on the future fertility of foetuses exposed in utero.
In Norah Spears’ laboratory, we have examined the effect of a variety of different chemotherapy drugs on the ovary, primarily through the use of ovarian tissue culture techniques. Tissue culture can be a powerful method for manipulating growth and development in a highly controlled manner. Here, I will describe the development of a novel embryonic mouse ovary culture technique that supports the growth of early pre-meiotic germ cells through early meiosis, up-to follicle formation, followed by the initiation of follicle growth, up-to the primary follicle stage. Using this technique, alongside other previously established ovary culture methods in the Spears laboratory, I have investigated how commonly prescribed chemotherapy agents can affect the mouse ovary, both prior to, and following the formation of the ovarian follicle, by examining the cell type affected, the developmental stage of germ cells most at risk and the time course of cell health. Finally, with a limited number of fertility preservation options available, especially for childhood cancer patients, the ideal solution will be if the ovary can be protected from the damaging effect of chemotherapy drugs. My current work therefore focuses on examining the potential for tyrosine kinase inhibitors to protect the ovary against chemotherapy induced damage.