Abstract
Purpose
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 and whether these effects depend on type of chemotherapy and duration of exposure.
Methods
Pregnant 8-week-old female BL6 mice 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. The extent of this damage depends upon 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. 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.
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Acknowledgements
We would like to thank the people from the Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) and the animal caretakers at the Laboratory Animal Centre of the NKI for performing the intervention studies.
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Internal funding was used to purchase the mice.
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Study concept and design: CL, FA, and MV; material preparations and data collection: TS, JYS, and VW; data analysis and interpretation: TS, JYS, CL; writing—original draft: TS; critical revision: all authors; approval of final manuscript: all authors.
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Schuurman, T., Song, JY., Wolters, V. et al. Effects of chemotherapy on ovaries of pregnant mice. Arch Gynecol Obstet 307, 1163–1176 (2023). https://doi.org/10.1007/s00404-022-06793-w
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DOI: https://doi.org/10.1007/s00404-022-06793-w