Reproduction Abstracts

Introduction: The use of the chemotherapeutic agent etoposide in pregnancy is considered to be relatively safe during the second and third trimesters. However, the drug does have detrimental effects on oocytes undergoing meiosis II. Similar effects on oocytes in meiosis I may have a clinical impact on the fertility of women exposed to the drug in utero, during critical stages of ovarian development. This study aims to examine the effects of etoposide exposure during early meiosis using a mouse embryonic whole ovary culture system.

Methods: Day 13.5 embryonic mouse ovaries were collected, with oocytes then initiating meiosis. Ovaries were cultured on agar blocks for a total of 12 days, and exposed to etoposide (50–150 ng/ml) for the first 6 days of culture; covering early prophase I. Newborn mouse ovaries, in which oocytes are already in meiotic arrest, were also exposed to etoposide (50–150 ng/ml) in a 6 day culture system. Immunofluorescent staining for γ-H2AX was carried out to localise double strand DNA breaks induced by etoposide exposure.

Results and discussion: Histological analysis revealed a detrimental effect of etoposide exposure on follicle numbers (150 ng/ml; P<0.001) in ovaries exposed during early prophase I, but not in those exposed after meiotic arrest. Double strand breaks were also visible in many cells, in ovaries exposed during early prophase I. Together, this indicates the possibility of effects on future reproductive potential of embryos exposed during early second trimester, but further work is required to determine the extent of damage which would occur in vivo.