Etoposide was found to damage ovarian tissue in the developing fetus in a study evaluating the effect of the drug on mouse ovarian tissue grown in vitro, a study published in the journal BMC Cancer has shown.1
Although etoposide, approved to treat several types of cancer, is considered safe during the second and third trimesters of pregnancy, information on its late effects on fertility of females exposed to the drug in the womb is limited. In this study, researchers at the University of Edinburgh collected fetal and neonatal ovaries from mice and cultured them in vitro to determine the effects of etoposide exposure.
Development of ovarian follicles begins at approximately week 17 of gestation and completes in late pregnancy. Each follicle encloses one oocyte, an immature egg cell, created from germ cells. A woman’s reproductive lifespan is predetermined by how many oocytes are developed in this process.
Fetal ovaries exposed to medium and high doses of etoposide before follicle formation resulted in declines of 72% to 90% of follicles, respectively, not only limiting fertility but also leading to potential early menopause in female children of women receiving the drug during pregnancy. After follicle formation, however, no significant adverse effects were seen, even at doses higher than those used to treat humans.
“Studies looking at the effects of taking chemotherapy drugs during pregnancy have focused on the immediate effects, such as increased miscarriage rates or severe fetal abnormalities,” explained Professor Norah Spears, of the University’s Centre for Integrative Physiology and lead researcher in the study. Our study suggests that chemotherapy may have significant late effects on the female babies of women who receive chemotherapy during pregnancy that only become apparent in the baby’s adulthood.2
1. Stefansdottir A, Johnston ZC, Powles-Glover N, Anderson RA, Adams IR, Spears N. Etoposide damages female germ cells in the developing ovary. BMC Cancer. 2016;16;482. doi: 10.1186/s12885-016-2505-9.
2. Biomed Central. Effects of chemotherapy on developing ovaries in female fetuses. EurekAlert! website. http://www.eurekalert.org/pub_releases/2016-08/bc-eoc080816.php. August 10, 2016. Accessed August 22, 2016.