Compound-dependent fetal toxicity after in utero exposure to chemotherapy in a pregnant mouse model

Abstract

Although chemotherapy is integrated in the treatment of second-trimester pregnant cancer patients, its potential cyto- and genotoxicity to fetal tissue remains unknown. To investigate any causal relation between in utero chemotherapy exposure and fetal toxicity, late-gestation pregnant BL6 mice were exposed to vehicle, or one of six chemotherapeutic compounds, used to treat pregnant cases: cyclophosphamide, carboplatin, cisplatin (alkylating agents), epirubicin, doxorubicin (anthracyclines) or paclitaxel (taxane). fetuses were euthanized at gestational day 18.5, after 48 hours of in utero exposure. Fetuses in utero exposed to alkylating agents presented with morphological changes in liver, bone marrow and thymus. Furthermore, decreased expression of Ki67, and increased expression of caspase-3 and P-H2AX markers, pointed to inhibited proliferation and increased apoptosis and DNA-double stranded breaks respectively, in several fetal tissues. Moderate toxicity was seen after in utero exposure to anthracyclines and taxanes. These findings emphasize the importance of investigating fetal toxicity in the clinical setting.