# Azithromycin prevents implantation failure via up-regulation of leukemia inhibitory factor in endotoxemic pregnant rats

**Authors:** Gonca Sonmez, Oznur Tufan Akarslan, Muhammed Hudai Culha, Tugba Melike Parlak, Burak Dik, Ayse Er

PMC · DOI: 10.22038/ijbms.2025.85311.18435 · Iranian Journal of Basic Medical Sciences · 2025-01-01

## TL;DR

Azithromycin may help prevent pregnancy loss by reducing harmful inflammation and boosting a key implantation factor in infected pregnant rats.

## Contribution

Azithromycin prevents implantation failure by modulating cytokine expression and upregulating leukemia inhibitory factor in endotoxemic pregnancy.

## Key findings

- LPS increased TNFα and IL-2 mRNA while decreasing LIF mRNA in uterine tissue.
- Azithromycin reversed LPS-induced changes in TNFα, IL-2, and LIF mRNA expressions.
- Azithromycin may prevent implantation failure by restoring cytokine balance in infected pregnancies.

## Abstract

Embryonic implantation is a complex and poorly understood process in which numerous cellular, hormonal, and molecular factors play critical roles. Infections in this process can result in pregnancy failure, such as implantation failure, infertility, and spontaneous abortion. Antibiotic use is necessary for infections. However, antibiotic use in pregnancy and the effect of the drug used on implantation are also conditions that must be considered. The implantation site is highly sensitive to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α, both of which can induce embryonic resorption. This study aimed to determine the effect of azithromycin (AZIT) on implantation failure, an important factor in early embryonic loss caused by LPS, by evaluating TNFα, interleukin (IL)-10, IL-2, and leukemia inhibitory factor (LIF) mRNA expressions in uterine tissue.

The study involved twenty-six female rats, divided into four groups: Control, Sham, LPS, and LPS+AZIT. Lipopolysaccharide was administered intravenously on the 5th day of pregnancy in the LPS and LPS+AZIT groups. AZIT was administered intraperitoneally in the LPS+AZIT group simultaneously with LPS. TNFα, IL-10, IL-2, and LIF mRNA expressions were evaluated in uterine tissue three hours post-LPS administration.

Lipopolysaccharide administration increased the expression of TNFα and IL-2 and decreased the expression of LIF. AZIT prevented the LPS-induced increase in TNFα and IL-2 mRNA expression and the decrease in LIF mRNA expression, all of which are involved in implantation failure.

AZIT may support the continuation of pregnancy by preventing the cytokine imbalance caused by infection at implantation.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IL10 (interleukin 10), IL2 (interleukin 2), LIF (LIF interleukin 6 family cytokine)
- **Chemicals:** azithromycin (PubChem CID 447043)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Lif (LIF, interleukin 6 family cytokine) [NCBI Gene 60584], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, Il2 (interleukin 2) [NCBI Gene 116562]
- **Diseases:** implantation failure (MESH:D051437), embryonic loss (MESH:D020964), Infections (MESH:D007239), abortion (MESH:D000026), infertility (MESH:D007246)
- **Chemicals:** AZIT (MESH:D017963), LPS (MESH:D008070)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12340416/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12340416/full.md

## References

45 references — full list in the complete paper: https://tomesphere.com/paper/PMC12340416/full.md

---
Source: https://tomesphere.com/paper/PMC12340416