Abstract
OBJECTIVES: This study compared the effects of daidzein (DZD) and 17-β-estradiol (E2) on uterine histopathology, expression of endometrial cancer-related genes, and anti-oxidant status in ovariectomized (OVX) rats. MATERIALS AND METHODS: Thirty rats were divided into five groups (n=6): Sham, OVX, OVX+E2 (10 μg/kg/day), OVX+DZD (20 mg/kg/day), and DZD-only. After 50 days of treatment, uterine tissues were analyzed for histopathological changes, mRNA expression of ERα, ERβ, PTEN, EZH2, and Ki67, and oxidative stress markers (TAC, SOD, CAT, and MDA). RESULTS: Ovariectomy induced endometrial atrophy, significantly downregulated the expression of all target genes (ERα, ERβ, PTEN, EZH2, and Ki67), decreased SOD and CAT activity and TAC level, and increased MDA. E2 treatment reversed these changes but induced hyperplastic effects. DZD administration significantly increased CAT and SOD activity and elevated ERβ and Ki67 expression compared with the OVX group. Crucially, DZD prevented uterine atrophy without inducing hyperplasia. CONCLUSION: DZD demonstrated a potentially beneficial effect by improving uterine anti-oxidant capacity and preventing atrophy, but without the hyperplastic changes associated with estradiol. These findings suggest that DZD may be a safer alternative for managing hypoestrogenic conditions, warranting further investigation.