# S100A8 regulated by estrogen improves injured endometrial epithelium reconstruction by promoting tight junction formation and stromal cell transformation

## TL;DR

This study shows that S100A8, regulated by estrogen, helps repair damaged endometrial tissue by improving cell junctions and transforming stromal cells into epithelial cells.

## Contribution

The study reveals a novel role of S100A8 in endometrial repair, compensating for estrogen's limited effectiveness in injured tissue.

## Key findings

- S100A8 administration improved injured endometrial epithelium morphology and cell junction formation.
- S100A8 promotes stromal cell transformation into epithelial cells and reverse migration of immune cells.
- Estrogen has limited regulatory effects on severely injured endometrium via self-S100A8.

## Abstract

Estrogen is used for endometrial repair; however, it has limited effectiveness. Cytokine S100A8 expression is affected by estrogen and is involved in regulating the damage repair. We aimed to confirm the effects of S100A8 and explore its mechanisms during the reconstruction of the injured endometrium. We investigated the effects of estrogen on S100A8 expression in healthy endometrium. A rat model of endometrial injury and cultured primary endometrial cells were used to determine the pleiotropic effects of S100A8 on endometrial epithelial repair. Estrogen regulated the recruitment of S100A8-positive immune cells (S100A8-PICs) and the release of S100A8 in the healthy endometrium, but estrogen plays a limited role in regulating seriously injured endometrium via self-S100A8. S100A8 administration to the uterine cavity significantly improved the morphology of injured epithelium; influenced the reverse migration of S100A8-PICs; and promoted epithelial localization of proliferating cells, cell junction formation, and transformation of stromal cells to epithelial cells. S100A8 in the uterine cavity has pleiotropic effects that improve endometrial epithelial reconstruction and can compensate for the deficiency in estrogen repair regulation.

The online version contains supplementary material available at 10.1038/s41598-025-08530-0.