Endocrine Abstracts

Background/aims: Obesity is a major risk factor for endometrial cancer with estrogens in combined oral contraceptives enhancing the severity of the disease. This study aims to explore the effect of synthetic estrogen ethinylestradiol (EE2) commonly used in oral contraceptives, on endometrial morphology and regulatory markers in diet-induced obese mice.

Methods: Female TO mice were on a high-fat diet (HFD) for 27 weeks. Three groups (n = 5) were given different concentrations of EE2 (3.5ng/ml, 88ng/ml or 4000ng/ml) for 28 days. Estrous cycling and metabolic parameters were measured at regular intervals. UTH tissues underwent H&E and immunohistochemistry staining for analysis.

Results: HFD significantly (P < 0.01) increased body weight while high-dose EE2 significantly (P < 0.01) decreased body weight compared to HFD. High-dose EE2 significantly (P < 0.05) decreased blood glucose compared to ND mice. HFD and all EE2-doses significantly increased cumulative energy intake (P < 0.01 and P < 0.001). Medium-dose EE2 significantly reduced gland number in UTH compared to ND (P < 0.05). HFD and all EE2-doses significantly (P < 0.001) increased gland diameter compared to controls. HFD, medium and high-dose EE2 significantly (P < 0.05 and P < 0.01) decreased epithelium thickness compared to ND and HFD groups. Myometrium thickness also decreased (P < 0.05 and P < 0.01) after medium and high-dose EE2 compared to ND and HFD mice. Low and medium-dose EE2 significantly increased CTCF of FOXA2 compared to HFD (P < 0.01) and medium and high-dose increased compared to ND (P < 0.05). Medium and high-dose EE2 significantly decreased CTCF of SOX-9 compared to ND and HFD (P < 0.05, P < 0.01 and P < 0.001). All EE2-doses significantly decreased CTCF of ZO-1 compared to HFD (P < 0.05, P < 0.01 and P < 0.001) and medium-dose compared to ND (P < 0.001).

Conclusion: This data highlights the impact of estrogen in the regulation of endometrial health and its possible contribution to the development of endometrial cancer. Further understanding of mechanistic effects of EE2 might help in the treatment of estrogen-dependent endometrial cancers.