# Endometrial Cell Senescence and Recurrent Spontaneous Abortion: Biomarker Potential of UCP2 and GSR

## TL;DR

This study identifies UCP2 and GSR as potential biomarkers for recurrent spontaneous abortion, linking endometrial cell senescence to immune responses and oxidative stress.

## Contribution

The study introduces UCP2 and GSR as novel biomarkers for recurrent spontaneous abortion, linking them to oxidative stress and immune activity.

## Key findings

- UCP2 and GSR are significantly upregulated in endometrial cell senescence linked to recurrent spontaneous abortion.
- Natural killer and T cell activity is increased in affected tissues, indicating an immune component.
- Dexamethasone and menadione are predicted as potential treatments based on drug analysis.

## Abstract

This study explores the molecular mechanisms driving recurrent spontaneous abortion, a condition affecting 1–5% of women of reproductive age, with 40–50% of cases unexplained. Focusing on endometrial cell senescence, a process linked to irreversible cell cycle arrest, the research identifies uncoupling protein 2 (UCP2) and glutathione reductase (GSR) as key contributors to this pathology. By analyzing transcriptome data from the Gene Expression Omnibus database, 21 genes associated with cellular senescence were found to be differentially expressed, with UCP2 and GSR significantly upregulated. These findings were validated using a hydrogen peroxide-induced senescence model in human endometrial stromal cells. Diagnostic potential was confirmed through receiver operating characteristic curve analysis, showing promising results for both UCP2 and GSR. The study also observed increased activity of natural killer and T cells in affected tissues, pointing to an immune component in recurrent spontaneous abortion. Drug prediction analysis highlighted dexamethasone and menadione as potential treatments. These insights suggest that oxidative stress-induced senescence plays a critical role in recurrent spontaneous abortion, with UCP2 and GSR as promising biomarkers and therapeutic targets to improve endometrial health and reduce miscarriage risk. Further clinical studies are needed to validate these findings and explore their therapeutic applications.

The online version contains supplementary material available at 10.1007/s43032-025-02023-1.