With cancer survivorship at an all-time high, increased attention has been placed on uncovering the off-target side-effects of cancer treatments, like infertility. It is well-established that chemotherapies have profound impacts on ovarian function; however, impacts to the uterus are unclear. An adequately prepared endometrium – essential for pregnancy success – requires complex changes. Decidualisation describes the differentiation of uterine stromal cells into secretory cells; essential for trophoblast invasion, spiral-artery remodelling, and pregnancy establishment. Therefore, the aim of this study was to assess the impact of chemotherapy on decidualisation.
To study the impact of chemotherapy on the uterus independent of ovarian influence, adult female C57BL6/J mice were ovariectomised and treated with a single-dose of cisplatin (5mg/kg) or vehicle control (n=8/group), followed by artificial decidualisation 14 days later. Additionally, decidualisation was induced in a human endometrial stromal cells (tHESC) treated with 70µM cisplatin (IC50) or vehicle control. Uterine-to-bodyweight ratios and qPCR analysis of key markers were used to assess decidualisation.
Decidualisation was induced in vivo (control: 75% vs. cisplatin: 88%). Uterine-to-bodyweight ratios were similar between control (0.010±0.003) and cisplatin-treated groups (0.008±0.002), suggesting single-dose cisplatin does not significantly impact decidualisation. No significant differences were observed in the expression of decidualisation markers Bmp2, Hoxa10, Esr1, or Pgr in uterine tissues. Significant increases in BMP2 (p<0.05), HOXA10 (p<0.01), and PGR (<0.001) expression in cultured tHESC demonstrated decidualisation was induced, but no significant differences were observed between untreated and cisplatin-treated cells. Increased γH2AX/TUNEL staining was observed in cisplatin-treated uterine tissues, suggesting elevated levels of DNA damage/apoptosis post-treatment.
Collectively, these data suggest single-dose cisplatin does not impact decidualisation. As women typically receive multi-dose regimens clinically, this should be the focus of future studies. Nevertheless, no available fertility preservation options exist to protect the uterus, thus characterising any impacts of chemotherapy on uterine function must be prioritised.