Introduction/Background It is unknown if future fertility is compromised by the administration of chemotherapy during pregnancy. The aim of this study was to identify if chemotherapy affects the maternal ovaries during pregnancy, whether these effects depend on type of chemotherapy and duration of exposure, and if pregnancy protects against chemotherapy-induced gonadotoxicity.
Methodology Pregnant 8-week-old female BL6 mice (N=115) were exposed to 6 different single chemotherapeutic agents (carboplatin, cisplatin, paclitaxel, epirubicin, doxorubicin or cyclophosphamide) or saline at gestational day (GD) 13.5. The mice were sacrificed at GD 15.5 or GD 18.5. Ovaries were assessed by histopathology and immunohistochemistry. Follicle count was determined per follicle stage and per treatment modality.
Results Maternal ovarian damage was demonstrated by the presence of apoptosis and necrosis in preantral follicles (figure 1). The extent of this damage depends on type of chemotherapy and duration of exposure (2 or 5 days). After short exposure, 81% of ovaries showed histopathologic signs of damage compared to 36% after long exposure, which might suggest a transient effect. Loss of primordial follicles (PMFs) was observed after both short and long exposure, with a reduction of more than 70%. Evidence of DNA damage, as demonstrated by phospho-H2AX expression, was present in 23% (range 0–89%) of PMFs exposed to chemotherapy, but only in the short exposure group (figure 2). Overall, the least damage was seen after administration of paclitaxel.
Conclusion Despite physiological ovarian function suppression during gestation, chemotherapy-induced damage of the ovaries occurs in pregnant mouse models, potentially affecting future fertility.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.