Although ovarian toxicity of chemotherapy is well characterised, its impacts on the uterus, specifically the endometrium, remains unclear. Following treatment, women often experience poor pregnancy outcomes, such as low birth weight and spontaneous abortion, suggesting uterine dysfunction(1,2). However, it difficult to determine the precise impacts of single agents on uterine function in women because clinical research is confounded by the use of varied combination treatments.
Adult female C57/Bl6 mice received a single dose of cisplatin (5mg/kg) or vehicle control (saline) followed by ovariectomy to control for diminished ovarian endocrine function caused by chemotherapy treatment. Mice were then artificially decidualised and uterine to body weight ratios compared between groups. Gene and protein expression of decidualisation markers (Bmp2, Hoxa10, Pgr, Esr-1, Prl, Igfbp-1, Desmin, Klf4) were analysed. In vitro, human endometrial epithelial and stromal cells were exposed to varying concentrations of cisplatin to determine sensitivity and DNA damage.
Uterine to body weight ratios, and the expression of decidualisation markers, were similar between treated and control mice. In vitro, human endometrial epithelial and stromal cells were susceptible to DNA damage induced by cisplatin, as indicated by positive γH2AX immunofluorescent labelling.
These data indicate that a single dose of cisplatin does not impact the extent of decidualisation in mice in vivo. Future studies in mice will determine if the downstream processes in pregnancy establishment are affected by prior cisplatin treatment, such as placentation. Multidose treatments will also be used to model clinically relevant regimens. Furthermore, the functional capabilities of cisplatin-damaged human endometrial stromal cells will be evaluated by artificial decidualisation in vitro. This research will allow clinicians to better inform patients on impacts to their reproductive capacity following cancer treatment.