The number of childhood (from birth to adolescence) cancer survivors increases because of increased cancer incidence and a slightly more significant decrease in the mortality rate from cancer therapy. A unique side effect of concern on these cancer survivors from cancer therapy (e.g., chemotherapy and radiotherapy) is fertility impairment. Some chemotherapeutics drugs have been shown to target ovarian follicles to impair female fertility. The corpus luteum (CL) is normally developed from an ovulated follicle for producing progesterone (P4) to support early pregnancy. To fill in the knowledge gap about effects of chemotherapy on the CL, we tested the hypothesis that chemotherapy could adversely affect the CL using doxorubicin (DOX) as a representative chemotherapeutic drug in mice. We found varying effects in serum P4 levels, as well as varying effects in key aspects of CL function. CLs from DOX-treated mice with low P4 levels had less defined luteal cords, disrupted expression pattern of collagen IV (a marker of the basal lamina of endothelial cells), and reduced expression of StAR (steroidogenic acute regulatory protein) in luteal cells. A major focus in oncofertility is studying the gonadotoxic effects of chemotherapies on the ovary (sans the CL), however the uterus also plays a critical role in the future reproductive health of premenopausal patients. We showed that a single, human-relevant dose of doxorubicin (10 mg/kg, single dose) in young adult ovariectomized CD-1 mice had a long-term effect on uterine transcriptome to E2 treatment (Andersen CL et al, 2018). Since some of the differentially expressed genes are associated with uterine receptivity, we hypothesize that chemotherapy could disrupt uterine receptivity for embryo implantation. To test this hypothesis, ovariectomized C57BL6J mice are treated with vehicle (negative control), doxorubicin (2 mg/kg, 5 daily doses), or doxorubicin (10 mg/kg, single dose, positive control) starting on PND30. Decidualization is a uterine response to an implanting embryo and an indication of uterine receptivity. We use artificial decidualization to determine uterine receptivity, visualizing the accumulation of blue-dye in the decidual sites of a receptive uterus. Preliminary data show that the above chemotherapeutic regimens have varied adverse effects on uterine receptivity.
