MOTHERS taking the chemotherapy drug etoposide during pregnancy could reduce the reproductive lifespan of their daughters. This is according to the findings of an animal study that examined the effects of the drug on the development of ovarian tissue in mice.
Etoposide is used to treat lung cancer, ovarian cancer, leukaemia, and lymphoma and has now been found to damage the development of mouse ovary tissue grown in a laboratory. It was also found to affect the germ cells, which form structures of follicles that determine how many eggs will be released over a lifetime. If these findings were replicated in human studies it could mean that the use of the anti-cancer drug by mothers during pregnancy would cause early menopause in their daughters.
Researchers at the University of Edinburgh in the UK cultured fetal ovaries from embryonic Day 13.5 CD1 mice with 50–150 ng/mL of etoposide and neonatal ovaries from postnatal Day 0 CD1 mice with 50–200 ng/mL of the drug. The results showed a near-complete absence of the development of healthy follicles when fetal ovaries were treated with etoposide prior to follicle formation. In neonatal ovaries, when follicle formation was already complete, the drug had no significant adverse effect on follicle numbers and health.
“If the results we have seen in these mouse studies are replicated in human tissue, it could mean that girls born to mums who are taking etoposide during pregnancy have a reduced fertility window,” explained the lead researcher, Prof Norah Spears, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
Approximately one out every 1,000 pregnant women are diagnosed with cancer, often requiring consideration for the use of chemotherapy during pregnancy. Chemotherapy is avoided in the first 12–14 weeks of pregnancy because of significant harmful risks associated with the development of the fetus, but its use is considered relatively safe during the second and third trimesters. Follicular development, which determines the reproductive lifespan of the female, begins to take place around Week 17 of gestation. This has led the authors of the research to express concern for the potential implications of their findings, especially as etoposide is currently prescribed to pregnant woman, because the damaging effects of etoposide on the development of ovarian tissue in mice might have a similar effect on human fetal ovaries.
Prof Norah Spears, Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.