# Alleviation effect of glycyrrhetinic acid on zearalenone-induced reproductive toxicity in replacement gilts

**Authors:** Li-Tao Che, Ahmed H. El-Sappah, Heba Allah M. Elbaghdady, Yong-Jun Ren, Qi-Fan Wu, Wan-Hai Zhou, Ya-ru Yang, Rong-Fu Guo

PMC · DOI: 10.3389/fvets.2025.1636738 · 2025-10-13

## TL;DR

Glycyrrhetinic acid helps reduce reproductive harm caused by zearalenone in young pigs by improving hormone levels and liver function.

## Contribution

This study demonstrates that glycyrrhetinic acid can alleviate zearalenone-induced reproductive toxicity in replacement gilts.

## Key findings

- Glycyrrhetinic acid advanced puberty onset and improved uterine and ovarian development impaired by zearalenone.
- Glycyrrhetinic acid elevated hormone levels and reduced liver damage caused by zearalenone exposure.
- Glycyrrhetinic acid downregulated zearalenone-induced upregulation of HSD genes in liver and duodenum.

## Abstract

This study investigated whether glycyrrhetinic acid (GA) can alleviate the reproductive toxicity of Zearalenone (ZEN) in replacement gilts.

Eighty Landrace × Yorkshire gilts were randomly assigned to four dietary groups: control (basal diet), ZEN (1 mg/kg), GA (400 mg/kg), and ZEN + GA (1 mg/kg ZEN + 400 mg/kg GA).

The onset of estrus advanced significantly in all treatment groups, with the GA and ZEN + GA groups showing the most pronounced changes. Puberty onset occurred earlier in the ZEN group and was further advanced by GA supplementation. ZEN exposure impaired uterine and ovarian development, while GA improved organ development and mitigated the abnormalities in the ZEN + GA group. Hormonal analysis revealed that ZEN reduced estradiol (E2) and luteinizing hormone (LH), whereas GA elevated all measured hormones. The ZEN + GA group showed a partial recovery in hormone levels, excluding E2. Histological examination of liver tissue in the ZEN group revealed focal hepatocellular necrosis and lymphocyte infiltration, which GA notably attenuated. ZEN upregulated 3α/3β/17β-hydroxysteroid dehydrogenase (HSD) gene expression in the liver and duodenum, while GA co-administration downregulated most HSD genes except hepatic 3α-HSD.

These findings suggest that GA can alleviate ZEN-induced reproductive toxicity via modulation of endocrine and hepatic metabolic pathways.

## Linked entities

- **Chemicals:** glycyrrhetinic acid (PubChem CID 10114), zearalenone (PubChem CID 5281576), estradiol (PubChem CID 450)

## Full-text entities

- **Genes:** AKR1C4 (aldo-keto reductase family 1 member C4) [NCBI Gene 1109] {aka 3-alpha-HSD, C11, CDR, CHDR, DD-4, DD4}
- **Diseases:** necrosis (MESH:D009336), reproductive toxicity (MESH:D060737)
- **Chemicals:** E2 (MESH:D004958), GA (MESH:D006034), ZEN (MESH:D015025)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12554610/full.md

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Source: https://tomesphere.com/paper/PMC12554610