# Comparative effects of estradiol and daidzein on the expression of endometrial cancer-related genes and histopathological parameters in the uterus of ovariectomized rats

**Authors:** Vahid Setayesh, Asma Neisy, Maryam Niknam, Zahra Khoshdel, Farhad Koohpeyma, Sanaz Alaee, Fatemeh Zal

PMC · DOI: 10.22038/ijbms.2025.89681.19349 · Iranian Journal of Basic Medical Sciences · 2026-01-01

## TL;DR

This study compares how estradiol and daidzein affect the uterus in rats that had their ovaries removed, focusing on cancer-related genes and tissue changes.

## Contribution

The study reveals that daidzein improves antioxidant status and prevents uterine atrophy without causing hyperplasia, unlike estradiol.

## Key findings

- Daidzein increased antioxidant enzyme activity and prevented uterine atrophy in ovariectomized rats.
- Daidzein elevated ERβ and Ki67 gene expression without inducing hyperplasia.
- Estradiol reversed ovariectomy-induced changes but caused hyperplastic effects.

## Abstract

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.

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).

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.

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.

## Linked entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099], ESR2 (estrogen receptor 2) [NCBI Gene 2100], PTEN (phosphatase and tensin homolog) [NCBI Gene 5728], EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146], Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345]
- **Chemicals:** daidzein (PubChem CID 5281708), 17-β-estradiol (PubChem CID 154274)
- **Diseases:** endometrial cancer (MONDO:0002447)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Esr1 (estrogen receptor 1) [NCBI Gene 24890] {aka ER-alpha, Esr, RNESTROR}, Pten (phosphatase and tensin homolog) [NCBI Gene 50557] {aka MMAC1, Mmac, TEP1}, Ezh2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 312299], Esr2 (estrogen receptor 2) [NCBI Gene 25149] {aka ER-beta, ERbeta, Erb2}
- **Diseases:** endometrial cancer (MESH:D016889), endometrial atrophy (MESH:D014591), hyperplasia (MESH:D006965), atrophy (MESH:D001284)
- **Chemicals:** daidzein (MESH:C004742), MDA (MESH:D015104), DZD (-), 17-beta-estradiol (MESH:D004958)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12867098/full.md

## References

58 references — full list in the complete paper: https://tomesphere.com/paper/PMC12867098/full.md

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Source: https://tomesphere.com/paper/PMC12867098